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Ischemic stroke (see the image below) is characterized by the sudden loss of blood circulation to an area of the
brain, resulting in a corresponding loss of neurologic function. Acute ischemic stroke is caused by thrombotic or
embolic occlusion of a cerebral artery and is more common than hemorrhagic stroke.
Maximum intensity projection (MIP) image from a computed tomography angiogram (CTA)
demonstrates a filling defect or high-grade stenosis at the branching point of the right middle cerebral artery (MCA) trunk
(red circle), suspicious for thrombus or embolus. CTA is highly accurate in detecting large- vessel stenosis and occlusions,
which account for approximately one third of ischemic strokes.
See Acute Stroke, a Critical Images slideshow, for more information on incidence, presentation, intervention,
and additional resources.
Essential update: Study indicates intra-arterial treatment improves functional recovery in acute
ischemic stroke
A randomized clinical trial from the Netherlands indicates that endovascular intervention benefits functional
outcomes in patients with acute ischemic stroke resulting from a proximal intracranial arterial occlusion. In the
study, by Berkhemer et al, 500 patients were randomized to receive intra-arterial treatment (within 6 hours of
symptom onset) or usual treatment alone. Although 89% of the patients were treated with tissue-type
plasminogen activator (t-PA) prior to randomization, only those who were found on computed tomography (CT)
angiography to still have a proximal arterial occlusion were entered into the study. In most of the patients who
received intra-arterial treatment, the procedure was performed with latest-generation stent retrievers. [1, 2]
The investigators found that at 90 days, the rate of functional independence (modified Rankin scale score of 02) in the intra-arterial treatment group was 32.6%, compared with 19.1% in the usual-treatment-only group,
while after 5-7 days, the National Institutes of Health Stroke Scale (NIHSS) score was an average of 2.9 points
lower in the intra-arterial treatment patients than it was in the other group. The two groups did not differ
significantly with regard to the rate of morality or symptomatic intracerebral hemorrhage.
Cranial nerves
Motor function
Sensory function
Cerebellar function
Gait
Deep tendon reflexes
Language (expressive and receptive capabilities)
Mental status and level of consciousness
The skull and spine also should be examined, and signs of meningismus should be sought.
See Clinical Presentation for more detail.
Diagnosis
Emergent brain imaging is essential for confirming the diagnosis of ischemic stroke. Noncontrast computed
tomography (CT) scanning is the most commonly used form of neuroimaging in the acute evaluation of patients
with apparent acute stroke. The following neuroimaging techniques are also used:
Complete blood count (CBC): A baseline study that may reveal a cause for the stroke (eg,
polycythemia, thrombocytosis, thrombocytopenia, leukemia) or provide evidence of concurrent illness (eg,
anemia)
Basic chemistry panel: A baseline study that may reveal a stroke mimic (eg, hypoglycemia,
hyponatremia) or provide evidence of concurrent illness (eg, diabetes, renal insufficiency)
Coagulation studies: May reveal a coagulopathy and are useful when fibrinolytics or anticoagulants are
to be used
Cardiac biomarkers: Important because of the association of cerebral vascular disease and coronary
artery disease
Toxicology screening: May assist in identifying intoxicated patients with symptoms/behavior mimicking
stroke syndromes
Pregnancy testing: A urine pregnancy test should be obtained for all women of childbearing age with
stroke symptoms; recombinant tissue-type plasminogen activator (rt-PA) is a pregnancy class C agent
Arterial blood gas analysis: In selected patients with suspected hypoxemia, arterial blood gas defines
the severity of hypoxemia and may be used to detect acid-base disturbances
See Workup for more detail.
Management
The goal for the emergent management of stroke is to complete the following within 60 minutes of patient
arrival[3] :
Assess airway, breathing, and circulation (ABCs) and stabilize the patient as necessary
Complete the initial evaluation and assessment, including imaging and laboratory studies
Initiate reperfusion therapy, if appropriate
Critical treatment decisions focus on the following:
Fibrinolytic therapy
Antiplatelet agents [4, 5]
Mechanical thrombectomy
Treatment of comorbid conditions may include the following:
Reduce fever
Correct hypotension/significant hypertension
Correct hypoxia
Correct hypoglycemia
Manage cardiac arrhythmias
Manage myocardial ischemia
Stroke prevention
Primary stroke prevention refers to the treatment of individuals with no previous history of stroke. Measures
may include use of the following:
Platelet antiaggregants
Statins
Exercise
Lifestyle interventions (eg, smoking cessation, alcohol moderation)
Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may
include use of the following:
Platelet antiaggregants
Antihypertensives
Statins
Lifestyle interventions
See Treatment and Medication for more detail.
Background
Acute ischemic stroke (AIS) is characterized by the sudden loss of blood circulation to an area of the brain,
typically in a vascular territory, resulting in a corresponding loss of neurologic function. Also previously called
cerebrovascular accident (CVA) or stroke syndrome, stroke is a nonspecific state of brain injury with neuronal
dysfunction that has several pathophysiologic causes. Strokes can be divided into 2 types: hemorrhagic or
ischemic. Acute ischemic stroke is caused by thrombotic or embolic occlusion of a cerebral artery. (See the
image below.)
Maximum intensity projection (MIP) image from a computed tomography angiogram (CTA)
demonstrates a filling defect or high-grade stenosis at the branching point of the right middle cerebral artery (MCA) trunk
(red circle), suspicious for thrombus or embolus. CTA is highly accurate in detecting large- vessel stenosis and occlusions,
which account for approximately one third of ischemic strokes.
Nearly 800,000 people suffer strokes each year in the United States; 82-92% of these strokes are ischemic.
Stroke is the fourth leading cause of adult death and disability, resulting in over $72 billion in annual cost. [6]
Ischemic and hemorrhagic stroke cannot be reliably differentiated on the basis of clinical examination findings
alone. Further evaluation, especially with brain imaging tests (ie, computed tomography [CT] scanning or
magnetic resonance imaging [MRI]), is required. (See Workup.)
Stroke categories
The system of categorizing stroke developed in the multicenter Trial of ORG 10172 in Acute Stroke Treatment
(TOAST) divides ischemic strokes into the following 3 major subtypes [4] :
Large-artery
Small-vessel, or lacunar
Cardioembolic infarction
Large-artery infarctions often involve thrombotic in situ occlusions on atherosclerotic lesions in the carotid,
vertebrobasilar, and cerebral arteries, typically proximal to major branches; however, large-artery infarctions
may also be cardioembolic.
Cardiogenic emboli are a common source of recurrent stroke. They may account for up to 20% of acute strokes
and have been reported to have the highest 1-month mortality.[7] (See Pathophysiology.)
Treatment
Recanalization strategies, including intravenous recombinant tissue-type plasminogen activator (rt-PA) and
intra-arterial approaches, attempt to establish revascularization so that cells in the ischemic penumbra (a
metabolically active region, peripheral to the ischemic area, where blood flow is reduced) can be rescued
before irreversible injury occurs. Restoring blood flow can mitigate the effects of ischemia only if performed
quickly.
The US Food and Drug Administration (FDA) has approved the use of rt-PA in patients who meet criteria set
forth by the National Institute of Neurologic Disorders and Stroke (NINDS). In particular, rt-PA must be given
within 3 hours of stroke onset and only after CT scanning has ruled out hemorrhagic stroke.
On the basis of recent European data, the American Heart Association and American Stroke Association
recommended expanding the window of treatment from 3 hours to 4.5 hours, with more stringent exclusion
criteria for the later period (see Treatment). The FDA has not yet approved rt-PA for this expanded indication,
but this has become the community standard in many institutions.
Other aspects of treatment for acute ischemic stroke include the following:
Treatment of neurologic complications
Anatomy
The brain is the most metabolically active organ in the body. While representing only 2% of the body's mass, it
requires 15-20% of the total resting cardiac output to provide the necessary glucose and oxygen for its
metabolism.
Knowledge of cerebrovascular arterial anatomy and the territories supplied by the cerebral arteries is useful in
determining which vessels are involved in acute stroke. Atypical patterns of brain ischemia that do not conform
to specific vascular distributions may indicate a diagnosis other than ischemic stroke, such as venous
infarction.
Arterial distributions
In a simplified model, the cerebral hemispheres are supplied by 3 paired major arteries, specifically, the
anterior, middle, and posterior cerebral arteries.
The anterior and middle cerebral arteries carry the anterior circulation and arise from the supraclinoid internal
carotid arteries. The anterior cerebral artery (ACA) supplies the medial portion of the frontal and parietal lobes
and anterior portions of basal ganglia and anterior internal capsule. (See the image below.)
Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral
artery (ACA) and Sylvian triangle. The pericallosal artery has been described to arise distal to the anterior communicating
artery or distal to the origin of the callosomarginal branch of the ACA. The segmental anatomy of the ACA has been
described as follows: the A1 segment extends from the internal carotid artery (ICA) bifurcation to the anterior communicating
artery; A2 extends to the junction of the rostrum and genu of the corpus callosum; A3 extends into the bend of the genu of
the corpus callosum; A4 and A5 extend posteriorly above the callosal body and superior portion of the splenium. The Sylvian
triangle overlies the opercular branches of the middle cerebral artery (MCA), with the apex representing the Sylvian point.
The middle cerebral artery (MCA) supplies the lateral portions of the frontal and parietal lobes, as well as the
anterior and lateral portions of the temporal lobes, and gives rise to perforating branches to the globus pallidus,
putamen, and internal capsule. The MCA is the dominant source of vascular supply to the hemispheres. (See
the images below.)
extending to the anterior and superior surface of the occipital horn of the lateral ventricle.
Frontal
view of a cerebral angiogram with selective injection of the left internal carotid artery (ICA) illustrates the anterior circulation.
The anterior cerebral artery (ACA) consists of the A1 segment proximal to the anterior communicating artery, with the A2
segment distal to it. The middle cerebral artery (MCA) can be divided into 4 segments: the M1 (horizontal segment) extends
to the anterior basal portion of the insular cortex (the limen insulae) and gives off lateral lenticulostriate branches, the M2
(insular segment), M3 (opercular branches), and M4 (distal cortical branches on the lateral hemispheric convexities).
The posterior cerebral arteries arise from the basilar artery and carry the posterior circulation. The posterior
cerebral artery (PCA) gives rise to perforating branches that supply the thalami and brainstem and the cortical
branches to the posterior and medial temporal lobes and occipital lobes. (See Table 1, below.)
The cerebellar hemispheres are supplied as follows:
Inferiorly by the posterior inferior cerebellar artery (PICA), arising from the vertebral artery (see the
image below)
VASCULAR TERRITORY
Structures Supplied
Medial lenticulostriate branches: caudate head, globus pallidus, anterior limb of internal capsule
Cortical branches: lateral frontal and parietal lobes lateral and anterior temporal lobe
Optic tracts, medial temporal lobe, ventrolateral thalamus, corona radiata, posterior limb of the internal capsule
Cortical branches: occipital lobes, medial and posterior temporal and parietal lobes
Anterolateral cerebellum
Pathophysiology
Acute ischemic strokes result from vascular occlusion secondary to thromboembolic disease (see Etiology).
Ischemia causes cell hypoxia and depletion of cellular adenosine triphosphate (ATP). Without ATP, there is no
longer the energy to maintain ionic gradients across the cell membrane and cell depolarization. Influx of sodium
and calcium ions and passive inflow of water into the cell lead to cytotoxic edema. [8, 9, 10]
Ischemic cascade
On the cellular level, the ischemic neuron becomes depolarized as ATP is depleted and membrane iontransport systems fail. Disruption of cellular metabolism also impairs normal sodium-potassium plasma
membrane pumps, producing an intracellular increase in sodium, which in turns increases intracellular water
content. This cellular swelling is referred to as cytotoxic edema and occurs very early in cerebral ischemia.
Cerebral ischemia impairs the normal sodium-calcium exchange protein also found on cell plasma membranes.
The resulting influx of calcium leads to the release of a number of neurotransmitters, including large quantities
of glutamate, which in turn activates N -methyl-D-aspartate (NMDA) and other excitatory receptors on other
neurons.
These neurons then become depolarized, causing further calcium influx, further glutamate release, and local
amplification of the initial ischemic insult. This massive calcium influx also activates various degradative
enzymes, leading to the destruction of the cell membrane and other essential neuronal structures. [12] Free
radicals, arachidonic acid, and nitric oxide are generated by this process, which leads to further neuronal
damage.
Ischemia also directly results in dysfunction of the cerebral vasculature, with breakdown of the blood-brain
barrier occurring within 4-6 hours after infarction. Following the barriers breakdown, proteins and water flood
into the extracellular space, leading to vasogenic edema. This produces greater levels of brain swelling and
mass effect that peak at 3-5 days and resolve over the next several weeks with resorption of water and
proteins.[13, 14]
Within hours to days after a stroke, specific genes are activated, leading to the formation of cytokines and other
factors that, in turn, cause further inflammation and microcirculatory compromise. [12] Ultimately, the ischemic
penumbra is consumed by these progressive insults, coalescing with the infarcted core, often within hours of
the onset of the stroke.
Infarction results in the death of astrocytes, as well as the supporting oligodendroglial and microglial cells. The
infarcted tissue eventually undergoes liquefaction necrosis and is removed by macrophages, with the
development of parenchymal volume loss. A well-circumscribed region of cerebrospinal fluidlike low density,
resulting from encephalomalacia and cystic change, is eventually seen. The evolution of these chronic changes
may be seen in the weeks to months following the infarction. (See the images below.)
[PCA] territory).
Vascular distributions: Anterior cerebral artery (ACA) infarction.
Diffusion-weighted image on the left demonstrates high signal in the paramedian frontal and high parietal regions. The
opposite diffusion-weighted image in a different patient demonstrates restricted diffusion in a larger ACA infarction involving
the left paramedian frontal and posterior parietal regions. There is also infarction of the lateral temporoparietal regions
bilaterally (both middle cerebral artery [MCA] distributions), greater on the left indicating multivessel involvement and
suggesting emboli.
Vascular distributions: Posterior cerebral artery (PCA) infarction.
The noncontrast computed tomography (CT) images demonstrate PCA distribution infarction involving the right occipital and
inferomedial temporal lobes. The image on the right demonstrates additional involvement of the thalamus, also part of the
PCA territory.
Vascular distributions: Anterior choroidal artery infarction. The diffusionweighted image (left) demonstrates high signal with associated signal dropout on the apparent diffusion coefficient (ADC)
map involving the posterior limb of the internal capsule. This is the typical distribution of the anterior choroidal artery, the last
branch of the internal carotid artery (ICA) before bifurcating into the anterior and middle cerebral arteries. The anterior
choroidal artery may also arise from the middle cerebral artery (MCA).
Etiology
Ischemic strokes result from events that limit or stop blood flow, such as extracranial or intracranial thrombotic
embolism, thrombosis in situ, or relative hypoperfusion. As blood flow decreases, neurons cease functioning.
Although a range of thresholds has been described, irreversible neuronal ischemia and injury is generally
thought to begin at blood flow rates of less than 18 mL/100 g of tissue/min, with cell death occurring rapidly at
rates below 10 mL/100 g of tissue/min
Risk factors
Risk factors for ischemic stroke include modifiable and nonmodifiable conditions. Identification of risk factors in
each patient can uncover clues to the cause of the stroke and the most appropriate treatment and secondary
prevention plan.
Nonmodifiable risk factors include the following (although there are likely many others):
Age
Race
Sex
Ethnicity
History of migraine headaches [21]
Fibromuscular dysplasia
Heredity: Family history of stroke or transient ischemic attacks (TIAs)
In a prospective study of 27,860 women aged 45 years or older who were participating in the Women's Health
Study, Kurth et al found that migraine with aura was a strong risk factor for any type of stroke. The adjusted
incidence of this risk factor per 1000 women per year was similar to those of other known risk factors, including
systolic blood pressure 180 mm Hg or higher, body mass index 35 kg/m2 or greater, history of diabetes, family
history of myocardial infarction, and smoking.[22]
For migraine with aura, the total incidence of stroke in the study was 4.3 per 1000 women per year, the
incidence of ischemic stroke was 3.4 per 1000 per year, and the incidence of hemorrhagic stroke was 0.8 per
1000 per year.
Modifiable risk factors include the following[23] :
Traditional risk factors, such as oxidized low-density lipoprotein (LDL) cholesterol and smoking, contribute to
this injury. It has been suggested, however, that infections may also contribute to endothelial injury and
atherosclerosis.
Host genetic factors, moreover, may modify the response to these environmental challenges, although inherited
risk for stroke is likely multigenic. Even so, specific single-gene disorders with stroke as a component of the
phenotype demonstrate the potency of genetics in determining stroke risk.
A number of genes are known to increase susceptibility to ischemic stroke. Mutations to the F2 and F5 genes
are relatively common in the general population and increase the risk of thrombosis. Mutations in the following
genes also are known to increase the risk of stroke:
A polymorphism at 2q36.3 was found in which adenosine substitution conferred a lower risk of ischemic stroke
in an additive fashion.[37] An additional study suggested an association between ischemic stroke and a locus on
12p13.[38]
For more information, see Genetic and Inflammatory Mechanisms in Stroke. In addition, complete information
on the following metabolic diseases and stroke can be found in the following main articles:
Methylmalonic Acidemia
Homocystinuria/Homocysteinemia
Fabry Disease
MELAS Syndrome
Hyperglycemia and Hypoglycemia in Stroke
Large-artery occlusion
Large-artery occlusion typically results from embolization of atherosclerotic debris originating from the common
or internal carotid arteries or from a cardiac source. A smaller number of large-artery occlusions may arise from
plaque ulceration and in situ thrombosis. Large-vessel ischemic strokes more commonly affect the MCA
territory, with the ACA territory affected to a lesser degree. (See the images below.)
angiogram (CTA) demonstrates a filling defect or high-grade stenosis at the branching point of the right middle cerebral
artery (MCA) trunk (red circle), suspicious for thrombus or embolus. CTA is highly accurate in detecting large- vessel
stenosis and occlusions, which account for approximately one third of ischemic strokes.
Lacunar strokes
Lacunar strokes represent 13-20% of all ischemic strokes. They result from occlusion of the penetrating
branches of the MCA, the lenticulostriate arteries, or the penetrating branches of the circle of Willis, vertebral
artery, or basilar artery. The great majority of lacunar strokes are related to hypertension. (See the image
below.)
Microatheroma
Lipohyalinosis
Fibrinoid necrosis secondary to hypertension or vasculitis
Hyaline arteriosclerosis
Amyloid angiopathy
Microemboli
Embolic strokes
Cardiogenic emboli may account for up to 20% of acute strokes. Emboli may arise from the heart, the
extracranial arteries, including the aortic arch or, rarely, the right-sided circulation (paradoxical emboli) with
subsequent passage through a patent foramen ovale.[39] Sources of cardiogenic emboli include the following:
Valvular thrombi (eg, in mitral stenosis or endocarditis or from use of a prosthetic valve)
Mural thrombi (eg, in myocardial infarction, atrial fibrillation, dilated cardiomyopathy, or severe
congestive heart failure)
Atrial myxoma
Acute myocardial infarction is associated with a 2-3% incidence of embolic strokes, of which 85% occur in the
first month after the infarction.[40] Embolic strokes tend to have a sudden onset, and neuroimaging may
demonstrate previous infarcts in several vascular territories or may show calcific emboli.
Cardioembolic strokes may be isolated, multiple and in a single hemisphere, or scattered and bilateral; the
latter 2 types indicate multiple vascular distributions and are more specific for cardioembolism. Multiple and
bilateral infarcts can be the result of embolic showers or recurrent emboli. Other possibilities for single and
bilateral hemispheric infarctions include emboli originating from the aortic arch and diffuse thrombotic or
inflammatory processes that can lead to multiple small-vessel occlusions. (See the image below.) [41, 42]
Thrombotic strokes
Thrombogenic factors may include injury to and loss of endothelial cells; this loss exposes the subendothelium
and results in platelet activation by the subendothelium, activation of the clotting cascade, inhibition of
fibrinolysis, and blood stasis. Thrombotic strokes are generally thought to originate on ruptured atherosclerotic
plaques. Arterial stenosis can cause turbulent blood flow, which can promote thrombus formation;
atherosclerosis (ie, ulcerated plaques); and platelet adherence. All cause the formation of blood clots that either
embolize or occlude the artery.
Intracranial atherosclerosis may be the cause of thrombotic stroke in patients with widespread atherosclerosis.
In other patients, especially younger patients, other causes should be considered, including the following [8, 43] :
Watershed infarcts
Vascular watershed, or border-zone, infarctions occur at the most distal areas between arterial territories. They
are believed to be secondary to embolic phenomenon or to severe hypoperfusion, as occurs, for example, in
carotid occlusion or prolonged hypotension. (See the image below.) [44, 45, 46]
Magnetic resonance imaging (MRI) scan was obtained in a 62-year-old man with
hypertension and diabetes and a history of transient episodes of right-sided weakness and aphasia. The fluid-attenuated
inversion recovery (FLAIR) image (left) demonstrates patchy areas of high signal arranged in a linear fashion in the deep
white matter, bilaterally. This configuration is typical for deep border-zone, or watershed, infarction, in this case the anterior
and posterior middle cerebral artery (MCA) watershed areas. The left-sided infarcts have corresponding low signal on the
apparent diffusion coefficient (ADC) map (right), signifying acuity. An old left posterior parietal infarct is noted as well.
Flow disturbances
Stroke symptoms can result from inadequate cerebral blood flow because of decreased blood pressure (and
specifically, decreased cerebral perfusion pressure) or as a result of hematologic hyperviscosity from sickle cell
disease or other hematologic illnesses, such as multiple myeloma and polycythemia vera. In these instances,
cerebral injury may occur in the presence of damage to other organ systems. For more information, see Blood
Dyscrasias and Stroke.
Epidemiology
Stroke is the leading cause of disability and the fourth leading cause of death in the United States. [47, 48] Each
year, approximately 795,000 people in the United States experience new (610,000 people) or recurrent
(185,000 people) stroke.[6]Epidemiologic studies indicate that 82-92% of strokes in the United States are
ischemic.
According to the World Health Organization (WHO), 15 million people suffer stroke worldwide each year. Of
these, 5 million die, and another 5 million are left permanently disabled. [49]
Men are at higher risk for stroke than women; white men have a stroke incidence of 62.8 per 100,000, with
death being the final outcome in 26.3% of cases, while women have a stroke incidence of 59 per 100,000 and
a death rate of 39.2%.
Although stroke often is considered a disease of elderly persons, one third of strokes occur in persons younger
than 65 years.[48] Risk of stroke increases with age, especially in patients older than 64 years, in whom 75% of
all strokes occur.
Prognosis
In the Framingham and Rochester stroke studies, the overall mortality rate at 30 days after stroke was 28%,
the mortality rate at 30 days after ischemic stroke was 19%, and the 1-year survival rate for patients with
ischemic stroke was 77%. However, the prognosis after acute ischemic stroke varies greatly in individual
patients, depending on the stroke severity and on the patients premorbid condition, age, and poststroke
complications.[4]
A study utilizing the large national Get With The Guidelines - Stroke registry found that the baseline National
Institutes of Health Stroke Scale (NIHSS) score was the strongest predictor of early mortality risk, even more
so than currently used mortality prediction models incorporating multiple clinical data. [51] Cardiogenic emboli are
associated with the highest 1-month mortality in patients with acute stroke.
The presence of computed tomography (CT) scan evidence of infarction early in presentation has been
associated with poor outcome and with an increased propensity for hemorrhagic transformation after fibrinolytic
therapy (see Pathophysiology).[5, 52, 53] Hemorrhagic transformation is estimated to occur in 5% of uncomplicated
ischemic strokes in the absence of fibrinolytic therapy, although it is not always associated with neurologic
decline. Indeed, hemorrhagic transformation ranges from the development of small petechial hemorrhages to
the formation of hematomas requiring evacuation.
Acute ischemic stroke has been associated with acute cardiac dysfunction and arrhythmia, which then correlate
with worse functional outcome and morbidity at 3 months. Data suggest that severe hyperglycemia is
independently associated with poor outcome and reduced reperfusion in fibrinolysis, as well as extension of the
infarcted territory.[54, 55, 56]
In stroke survivors from the Framingham Heart Study, 31% needed help caring for themselves, 20% needed
help when walking, and 71% had impaired vocational capacity in long-term follow-up. For more information,
see the Medscape Reference article Motor Recovery in Stroke.
Patient Education
Public education must involve all age groups. Incorporating stroke into basic life support (BLS) and
cardiopulmonary resuscitation (CPR) curricula is just one way to reach a younger audience. Avenues to reach
an audience with a higher stroke risk could include local churches, employers, and senior organizations to
promote stroke awareness.
The American Stroke Association (ASA) advises the public to be aware of the symptoms of stroke that are
easily recognized, including the sudden onset of any of the following, and to call 911 immediately:
Numbness or weakness of face, arm, or leg, especially on 1 side of the body
Confusion
Difficulty in speaking or understanding
Deterioration of vision in 1 or both eyes
Difficulty in walking, dizziness, and loss of balance or coordination
Severe headache with no known cause
In the spring of 2013, the ASA launched a stroke public education campaign that uses the acronym FAST to
teach the warning signs of stroke and the importance of calling 911, as follows:
F: Face drooping
A: Arm weakness
S: Speech difficulty
History
A focused medical history for patients with ischemic stroke aims to identify risk factors for atherosclerotic and
cardiac disease, including the following (see Etiology):
Hypertension
Diabetes mellitus
Tobacco use
High cholesterol
History of coronary artery disease, coronary artery bypass, or atrial fibrillation
In younger patients, elicit a history of the following:
Recent trauma
Coagulopathies
Illicit drug use (especially cocaine)
Migraines
Oral contraceptive use
Stroke should be considered in any patient presenting with an acute neurologic deficit (focal or global) or
altered level of consciousness. No historical feature distinguishes ischemic from hemorrhagic stroke, although
nausea, vomiting, headache, and a sudden change in the patients level of consciousness are more common in
hemorrhagic strokes.
Consider stroke in any patient presenting with acute neurologic deficit or any alteration in level of
consciousness. Common signs and symptoms of stroke include the abrupt onset of any of the following:
If the patient awakens with symptoms, then the time of onset is defined as the time at which the patient was
last seen to be without symptoms. Input from family members, coworkers, and bystanders may be required to
help establish the exact time of onset, especially in right hemispheric strokes accompanied by neglect or left
hemispheric strokes with aphasia.
Physical Examination
The goals of the physical examination are as follows:
Neurologic examination
With the availability of fibrinolytic therapy for acute ischemic stroke in selected patients, the physician must be
able to perform a brief but accurate neurologic examination on patients with suspected stroke syndromes. The
goals of the neurologic examination include the following:
Confirming the presence of a stroke syndrome (to be defined further with cranial CT scanning)
Distinguishing stroke from stroke mimics
Establishing a neurologic baseline should the patient's condition improve or deteriorate
Establishing stroke severity to assist in prognosis and therapeutic selection
Essential components of the neurologic examination include the following evaluations:
Cranial nerves
Motor function
Sensory function
Cerebellar function
Gait
Deep tendon reflexes
Language (expressive and receptive capabilities)
Mental status and level of consciousness
The skull and spine also should be examined, and signs of meningismus should be sought.
level of consciousness
Visual function
Motor function
Sensation and neglect
Cerebellar function
Language
The NIHSS is a 42-point scale. Patients with minor strokes usually have a score of less than 5. An NIHSS
score of greater than 10 correlates with an 80% likelihood of proximal vessel occlusions (as identified on CT or
standard angiograms). However, discretion must be used in assessing the magnitude of the clinical deficit and
resulting disability; for instance, if a patient's only deficit is mutism, the NIHSS score will be 3. Additionally, the
scale does not measure some deficits associated with posterior circulation strokes (ie, vertigo, ataxia). [58]
Table 2. National Institutes of Health Stroke Scale (Open Table in a new window)
1a
Category
Description
Score
Alert
Drowsy
Stuporous
Coma
1b
1c
Answers 1 correctly
Incorrect on both
Obeys 1 correctly
Incorrect on both
Normal
Forced deviation
No visual loss
Partial hemianopia
Complete hemianopia
Bilateral hemianopia
Normal
Minor
Partial
Complete
No drift
Drift
No movement
No drift
Drift
No movement
No drift
Drift
No movement
No drift
Drift
10
11
12
13
No movement
Absent
Present in 1 limb
Present in 2 limbs
Normal
Partial loss
Severe loss
No neglect
Partial neglect
Complete neglect
Normal articulation
No aphasia
describe pictures)
Severe aphasia
Mute
Total
0-42
* For limbs with amputation, joint fusion, etc, score 9 and explain.
** For intubation or other physical barriers to speech, score 9 and explain. Do not add 9 to the total score. NIH Stroke Scale (PDF)
Contralateral hemiparesis
Contralateral hypesthesia
Ipsilateral hemianopsia
Gaze preference toward the side of the lesion
Agnosia
Receptive or expressive aphasia, if the lesion occurs in the dominant hemisphere
Neglect, inattention, and extinction of double simultaneous stimulation, with some nondominant
hemisphere lesions
The MCA supplies the upper extremity motor strip. Consequently, weakness of the arm and face is usually
worse than that of the lower limb.
Syncope
Ataxia
A hallmark of posterior circulation stroke is the presence of crossed findings: ipsilateral cranial nerve deficits
and contralateral motor deficits. This contrasts with anterior stroke, which produces only unilateral findings.
Lacunar stroke
Lacunar strokes result from occlusion of the small, perforating arteries of the deep subcortical areas of the
brain. The infarcts are generally from 2-20 mm in diameter. The most common lacunar syndromes include pure
motor, pure sensory, and ataxic hemiparetic strokes. By virtue of their small size and well-defined subcortical
location, lacunar infarcts do not lead to impairments in cognition, memory, speech, or level of consciousness.
Diagnostic Considerations
Stroke mimics commonly confound the clinical diagnosis of stroke. One study reported that 19% of patients
diagnosed with acute ischemic stroke by neurologists before cranial CT scanning actually had noncerebrovascular causes for their symptoms.
The most frequent stroke mimics include the following:
Seizure (17%)
Systemic infection (17%)
Brain tumor (15%)
Toxic-metabolic disorders, such as hyponatremia and hypoglycemia (13%)
Positional vertigo (6%)
Conversion disorder
In the prehospital and emergency department (ED) settings, hypoglycemia is a common stroke mimic and is
particularly important to consider, since it can be readily detected and corrected. [59, 60] For more information,
seeHyperglycemia and Hypoglycemia in Stroke.
Ischemic versus hemorrhagic stroke
Although the definitive distinction of ischemic stroke from hemorrhagic stroke requires neuroimaging, a metaanalysis found that the following clinical findings increase the probability of hemorrhagic stroke [61] :
TIAs resolve within 60 minutes.[62] TIA can result from the same mechanisms as ischemic stroke. Data suggest
that roughly 10% of patients with TIA suffer stroke within 90 days and of those, half suffer stroke within 2 days.
[63, 64]
The classic definition of TIA included symptoms lasting as long as 24 hours. With advances in neuroimaging,
however, it now appears that many such cases represent minor strokes with resolved symptoms rather than
true TIAs. Thus, the current definition of TIA is based on tissue pathophysiology rather than symptom duration.
[62]
Approach Considerations
Imaging studies
Emergent brain imaging is essential for confirming the diagnosis of ischemic stroke. Noncontrast CT scanning
is the most commonly used form of neuroimaging in the acute evaluation of patients with apparent acute
stroke. A lumbar puncture is required to rule out meningitis or subarachnoid hemorrhage when the CT scan is
negative but the clinical suspicion remains high.
MRI with magnetic resonance angiography (MRA) has been a major advance in the neuroimaging of stroke.
MRI not only provides great structural detail but also can demonstrate early cerebral edema. In addition, MRI
has proved to be sensitive for detection of acute intracranial hemorrhage. However, MRI is not as available as
CT scanning is in emergencies, many patients have contraindications to MRI imaging (eg, pacemakers,
implants), and interpretation of MRI scans may be more difficult.
Carotid duplex scanning is one of the most useful tests in evaluating patients with stroke. Increasingly, it is
being performed earlier in the evaluation, not only to define the cause of the stroke but also to stratify patients
for either medical management or carotid intervention if they have carotid stenoses.
Digital subtraction angiography is considered the definitive method for demonstrating vascular lesions,
including occlusions, stenoses, dissections, and aneurysms.
For more information, see Cerebral Revascularization Imaging.
Laboratory studies
Extensive laboratory testing is not routinely required before decisions are made regarding fibrinolysis. Testing
can often be limited to blood glucose, plus coagulation studies if the patient is on warfarin, heparin, or one of
the newer antithrombotic agents (eg, dabigatran, rivaroxaban). A complete blood count (CBC) and basic
chemistry panel can be useful baseline studies.
Additional laboratory tests are tailored to the individual patient and may include the following:
Cardiac biomarkers
Toxicology screen
Fasting lipid profile
Erythrocyte sedimentation rate
Pregnancy test
MRI
Conventional (spin echo) MRI may take hours to produce discernible findings in acute ischemic stroke.
Diffusion-weighted imaging (DWI) is highly sensitive to early cellular edema, which correlates well with the
presence of cerebral ischemia. For this reason, many centers include DWI in their standard brain MRI protocol.
DWI MRI can detect ischemia much earlier than standard CT scanning or spin echo MRI can and provides
useful data in patients with stroke or transient ischemic attack (TIA). (See the image below.) [3, 67, 68, 69]
The most commonly used technique for perfusion MRI is dynamic susceptibility, which involves generating
maps of brain perfusion by monitoring the first pass of a rapid bolus injection of contrast through the cerebral
vasculature. Susceptibility-related T2 effects create signal loss in capillary blood vessels and parenchyma
perfused by contrast.
For more information on MRI and MRA in this setting, see Magnetic Resonance Imaging in Acute Stroke.
Based on the central volume principle, dynamic brain perfusion data can be obtained. Cerebral blood volume
(CBV), cerebral blood flow (CBF), and mean transit time (MTT) can be calculated using either perfusion MRI or
CT scanning. (See the image below.)
Regions of interest are selected for arterial and venous input (image on left) for
dynamic susceptibility-weighted perfusion magnetic resonance imaging (MRI). Signal-time curves (image on right) obtained
from these regions of interest demonstrate transient signal drop following the administration of intravenous contrast. The
information obtained from the dynamic parenchymal signal changes postcontrast is used to generate maps of different
perfusion parameters.
An evidence-based guideline from the American Academy of Neurology advises that DWI is more useful than
noncontrast CT scanning for the diagnosis of acute ischemic stroke within 12 hours of symptom onset and
should be performed for the most accurate diagnosis of acute ischemic stroke (level A). No recommendations
were made regarding the use of perfusion-weighted imaging (PWI) in diagnosing acute ischemic stroke, as
evidence to support or refute its value in this setting is insufficient. [70]
Intra-arterial contrast enhancement may be seen secondary to slow flow during the first or second day after
onset of infarction. This finding has been correlated with increased infarct volume size. [71]
A 48-year-old man presented with acute left-sided hemiplegia, facial palsy, and right-sided gaze
preference. Angiogram with selective injection of the right internal carotid artery demonstrates occlusion of the M1 segment
of the right middle cerebral artery (MCA) and A2 segment of the right anterior cerebral artery (ACA; images courtesy of
Concentric Medical).
Follow-up imaging after mechanical embolectomy in 48-year-old
man with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference demonstrates complete recanalization of
the right middle cerebral artery (MCA) and partial recanalization of the right A2 segment (images courtesy of Concentric
Medical).
Cerebral angiogram performed approximately 4.5 hours after symptom
onset in a 31-year-old man demonstrates an occlusion of the distal basilar artery (images courtesy of Concentric Medical).
Blood Studies
A CBC serves as a baseline study and may reveal a cause for the stroke (eg, polycythemia, thrombocytosis,
thrombocytopenia, leukemia) or provide evidence of concurrent illness (eg, anemia). The basic chemistry panel
serves as a baseline study and may reveal a stroke mimic (eg, hypoglycemia, hyponatremia) or provide
evidence of concurrent illness (eg, diabetes, renal insufficiency).
Coagulation studies may reveal a coagulopathy and are useful when fibrinolytics or anticoagulants are to be
used. In patients who are not taking anticoagulants or antithrombotics and in whom there is no suspicion for
coagulation abnormality, administration of rt-PA should not be delayed while awaiting laboratory results.
Cardiac biomarkers are important because of the association of cerebral vascular disease and coronary artery
disease. Additionally, several studies have indicated a link between elevations of cardiac enzyme levels and
poor outcome in ischemic stroke.
Toxicology screening may be useful in selected patients in order to assist in identifying intoxicated patients with
symptoms/behavior mimicking stroke syndromes. In patients with suspected hypoxemia, arterial blood gas
studies define the severity of hypoxemia and may detect acid-base disturbances. However, arterial punctures
should be avoided unless absolutely necessary in patients being considered for fibrinolytic therapy.
Approach Considerations
The central goal of therapy in acute ischemic stroke is to preserve tissue in the ischemic penumbra, where
perfusion is decreased but sufficient to stave off infarction. Tissue in this area of oligemia can be preserved by
restoring blood flow to the compromised area and optimizing collateral flow.
Recanalization strategies, including the administration of intravenous (IV) recombinant tissue-type plasminogen
activator (rt-PA) and intra-arterial approaches, attempt to establish revascularization so that cells in the
penumbra can be rescued before irreversible injury occurs. Restoring blood flow can mitigate the effects of
ischemia only if performed quickly.
Many surgical and endovascular techniques have been studied in the treatment of acute ischemic stroke.
Carotid endarterectomy has been used with some success in the acute management of internal carotid artery
occlusions, but no evidence supports its use acutely in ischemic stroke.
In addition to limiting the duration of ischemia, an alternative strategy is to limit the severity of ischemic injury
(ie, neuronal protection). Neuroprotective strategies are intended to preserve the penumbral tissues and to
extend the time window for revascularization techniques. At the present time, however, no neuroprotective
agents have been shown to impact outcomes in ischemic stroke.
Palliative care
Palliative care is an important component of comprehensive stroke care. Some stroke patients will simply not
recover, and others will be in a state of debilitation such that their comfort is the most humane and appropriate
therapeutic concern. Some patients have advance directives providing instructions for medical providers in the
event of severe medical illness or injury.
Clinical education
Prehospital care providers are essential to timely stroke care. Course curricula for prehospital care providers
are beginning to include more information on stroke than ever before. Through certification and Acute Cardiac
Life Support (ACLS) instruction, as well as continuing medical education classes, prehospital care providers
can remain current on stroke warning signs, prehospital stroke tools, and triage protocols in their region, and
can promote stroke awareness in their own communities.
Physician and nursing staff involved in the care of stroke patients, in the emergency department (ED) and in
the hospital, should participate in scheduled stroke education. This will help them to maintain the skills required
to treat stroke patients effectively and to remain current on medical advances for all stroke types.
Comorbidities
Comorbid medical conditions also need to be addressed. Hyperthermia is infrequently associated with stroke
but can increase morbidity. Administration of acetaminophen, by mouth or per rectum, is indicated in the
presence of fever (temperature >100.4F).
Oxygen supplementation
Supplemental oxygen is recommended when the patient has a documented oxygen requirement (ie, oxygen
saturation < 95%). In the small proportion of patients with stroke who are relatively hypotensive, administration
of IV fluid, vasopressor therapy, or both may improve flow through critical stenoses.
Fibrinolytic Therapy
The only fibrinolytic agent that has been shown to benefit selected patients with acute ischemic stroke is rt-PA.
While streptokinase may benefit patients with acute MI, in patients with acute ischemic stroke it has been
shown to increase the risk of intracranial hemorrhage and death.
Fibrinolytics (ie, rt-PA) restore cerebral blood flow in some patients with acute ischemic stroke and may lead to
improvement or resolution of neurologic deficits. Unfortunately, fibrinolytics may also cause symptomatic
intracranial hemorrhage. Other complications include potentially hemodynamically significant hemorrhage and
angioedema or allergic reactions.[3]
Inclusion/exclusion criteria
Therefore, if the patient is a candidate for fibrinolytic therapy, a thorough review of the inclusion and exclusion
criteria must be performed. The exclusion criteria largely focus on identifying risk of hemorrhagic complications
associated with fibrinolytic use. The American Heart Association/American Stroke Association (AHA/ASA)
inclusion guidelines for the administration of rt-PA are as follows [3] :
The patient and family understand the potential risks and benefits of therapy
Whereas these inclusion/exclusion criteria are from the original FDA approval, subsequent data and experience
have allowed some patients with what were previously considered relative contraindications to be safely
treated. Involvement of a physician with stroke expertise is critical for assessing the risk/benefit consideration
for these groups of patients.
Time to therapy
An rt-PA stroke study group from the National Institute of Neurologic Disorders and Stroke (NINDS) first
reported that the early administration of rt-PA benefited carefully selected patients with acute ischemic stroke.
[5]
The FDA subsequently approved the use of rt-PA in patients who met NINDS criteria. In particular, rt-PA had
to be given within 3 hours of stroke onset and only after CT scanning had ruled out hemorrhagic stroke.
Subsequently, fibrinolytic therapy administered 3-4.5 hours after symptom onset was found to improve
neurologic outcomes in the European Cooperative Acute Stroke Study III (ECASS III), suggesting a wider time
window for fibrinolysis.[83] On the basis of these and other data, in May 2009 the AHA/ASA revised the guidelines
for the administration of rt-PA after acute stroke, expanding the window of treatment from 3 hours to 4.5 hours
to provide more patients with an opportunity to benefit from this therapy.[83, 84, 85, 86]
Eligibility criteria for treatment during this later period are similar to those for earlier treatment but are more
stringent, with any 1 of the following serving as an additional exclusion criterion:
Hemorrhage risk
Although antiplatelet therapy may increase the risk for symptomatic intracerebral hemorrhage with fibrinolysis,
a study by Diedler et al that included 3782 patients who had received 1 or 2 antiplatelet drugs found that the
risk of intracerebral hemorrhage was small compared with the documented benefit of fibrinolysis. [91]These
researchers concluded that antiplatelet treatment should not be considered a contraindication to fibrinolysis,
although caution is warranted in patients receiving the combination of aspirin and clopidogrel.
Data regarding the safety of fibrinolytic therapy in patients taking dabigatran, rivaroxaban, or apixaban are not
available. Extreme caution should be used when considering fibrinolytic therapy in such patients.
Caution should also be exercised in the administration of rt-PA to patients with evidence of low attenuation
(edema or ischemia) involving more than a third of the distribution of the middle cerebral artery (MCA) on their
initial noncontrast CT scan; such patients are less likely to have a favorable outcome after fibrinolytic therapy
and are at higher risk for hemorrhagic transformation of their ischemic stroke. [52]
Ultrasound therapy
Researchers have studied the use of transcranial ultrasound as a means of assisting rt-PA in fibrinolysis. [92, 93] By
delivering mechanical pressure waves to the thrombus, ultrasound can theoretically expose more of the
thrombuss surface to the circulating fibrinolytic agent. Further research is necessary to determine the exact
role of transcranial Doppler ultrasound in assisting fibrinolytics in acute ischemic stroke.
For more information, see Thrombolytic Therapy in Stroke and Reperfusion Injury in Stroke.
Intra-arterial Reperfusion
There have been no completed human trials comparing intravenous versus intra-arterial administration of
fibrinolytics. Theoretically, intra-arterial delivery may produce higher local concentrations of the fibrinolytic agent
at lower total doses (and thus possibly lower the risk of a systemic bleed) and allow a longer therapeutic
window. However, the longer time for initiating intra-arterial administration may mitigate some of this advantage.
[3]
The Interventional Management of Acute Stroke Study (IMS-III) was halted for futility after showing no
additional benefit from intra-arterial therapies (rt-PA, mechanical thrombectomy, or both) compared with
intravenous rt-PA in patients with large-vessel occlusions. Additional analyses of the IMS III data are under way
to better understand the results and potentially identity subsets of patients who may benefit from the combined
approach.[94]
Intra-arterial fibrinolysis has been the traditional approach for patients with stroke from basilar artery occlusion.
However, results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry study in
592 patients, did not support unequivocal superiority of intra-arterial fibrinolysis over intravenous fibrinolysis. [95]
A meta-analysis of case studies involving a total of 420 patients with basilar artery occlusion did indicate that
recanalization was achieved more frequently with intra-arterial fibrinolysis than with intravenous fibrinolysis
(65% vs 53%), but the report also found that death and long-term disability were equally common with the 2
techniques.[96] These researchers concluded that intravenous fibrinolysis represents probably the best treatment
that can be offered to these patients in hospitals without a 24-hour interventional neuroradiologic service. [96]
Antiplatelet Agents
AHA/ASA guidelines recommend giving aspirin, 325 mg orally, within 24-48 hours of ischemic stroke onset. The
benefit of aspirin is modest but statistically significant and appears principally to involve the reduction of
recurrent stroke.[86]
The International Stroke Trial and the Chinese Acute Stroke Trial (CAST) demonstrated modest benefit from
the use of aspirin in the setting of acute ischemic stroke. The International Stroke Trial randomized 19,435
patients within 48 hours of stroke onset to treatment with aspirin 325 mg, subcutaneous heparin in 2 different
dose regimens, aspirin with heparin, and a placebo. The study found that aspirin therapy reduced the risk of
stroke recurrence within 14 days (2.8% vs 3.9%), with no significant excess of hemorrhagic strokes. [97, 98]
In CAST, which included 21,106 patients, aspirin treatment (160 mg/day) that was started within 48 hours of the
onset of suspected acute ischemic stroke and was continued in hospital for up to 4 weeks reduced mortality to
3.3%, compared with 3.9% with placebo. A separate study also found that the combination of aspirin and low
molecular-weight heparin did not significantly improve outcomes. [97]
Other antiplatelet agents have also been under evaluation for use in the acute presentation of ischemic stroke.
In a preliminary pilot study, abciximab given within 6 hours showed a trend toward improved outcome at 3
months.[99] However, the phase 3 Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II) was terminated
prematurely after 808 patients because of lack of efficacy and an increased rate of symptomatic or fatal
intracranial hemorrhage in patients receiving abciximab.[100]
in blood pressure over the first 24 hours without treatment. [86] The exceptions would be patients who have
comorbidities (eg, aortic dissection, acute myocardial infarction [MI], decompensated heart failure, hypertensive
emergency) that require emergent blood pressure management.
Thresholds for antihypertensive treatment in acute ischemic stroke patients who are not fibrinolysis candidates,
according to the 2013 ASA guidelines, are systolic blood pressure higher than 220 mm Hg or diastolic blood
pressure above 120 mm Hg.[86]In those patients, a reasonable goal is to lower blood pressure by 15% during
the first 24 hours after onset of stroke. Care must be taken to not lower blood pressure too quickly or
aggressively, since this could worsen perfusion in the penumbra.
Mechanical Thrombectomy
Mechanical clot disruption is an alternative for patients in whom fibrinolysis is ineffective or contraindicated.
Currently, 4 devices are approved by the FDA for the endovascular treatment of acute ischemic stroke, as
follows:
Merci Retriever (Concentric Medical, Mountain View, CA): Corkscrew-shaped device that captures and
engages clots
Penumbra System (Penumbra, Alameda, CA): Employs both aspiration and extraction
Solitaire FR Revascularization Device (Covidien, Dublin, Ireland): Stent-retriever system; combines the
ability to restore blood flow and retrieve clot
year 2 and 14.9% and 23.9% at year 3.[113] Rates of any stroke and of any major hemorrhage were also
significantly lower in the medical group than in the stenting group.
For more information, see Mechanical Thrombolysis in Acute Stroke.
Fever Control
Antipyretics are indicated for febrile stroke patients, since hyperthermia accelerates ischemic neuronal injury.
Substantial experimental evidence suggests that mild brain hypothermia is neuroprotective. The use of induced
hypothermia is currently being evaluated in phase II clinical trials. [115, 116, 117]
High body temperature in the first 12-24 hours after stroke onset has been associated with poor functional
outcome. However, results from the Paracetamol (Acetaminophen) in Stroke (PAIS) trial did not support the
routine use of high-dose acetaminophen (6 g daily) in patients with acute stroke, although post-hoc analysis
suggested a possible beneficial effect on functional outcome in patients admitted with a body temperature of
37-39 C.[118]
Patient position, hyperventilation, hyperosmolar therapy, and, rarely, barbiturate coma may be used, as in
patients with increased ICP secondary to closed head injury. Hemicraniectomy has been shown to decrease
mortality and disability among patients with large hemispheric infarctions associated with life-threatening
edema.[119, 120, 121, 122]
The American Heart Association and the American Stroke Association have released a guideline for the
management of cerebral and cerebellar infarction with brain swelling; recommendations include the following [123,
124]
:
Selected patients, including those able to handle an aggressive rehabilitation program, may benefit
from decompressive craniectomy; younger patients may benefit most, and surgery is not recommended for
patients older than 60 years
Clinical evidence of deterioration in swollen supratentorial hemispheric ischemic stroke includes new
or further impairment of consciousness, cerebral ptosis, and changes in pupillary size
In patients with swollen cerebellar infarction, level of consciousness decreases because of brainstem
compression; this decrease may include early loss of corneal reflexes and the development of miosis
Standardized definitions are needed to facilitate studies of incidence, prevalence, risk factors, and
outcomes
Identification of high-risk patients should include both clinical and neuroimaging data
Complex medical care of these patients includes airway management and mechanical ventilation,
blood pressure control, fluid management, and glucose and temperature control
In patients with swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure
monitoring or cerebrospinal fluid diversion is not indicated, but in patients who continue to deteriorate
neurologically, decompressive craniectomy with dural expansion should be considered
In patients with swollen cerebellar stroke who deteriorate neurologically, suboccipital craniectomy with
dural expansion should be performed
After a cerebellar infarct, performance of ventriculostomy to relieve obstructive hydrocephalus should
be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar
displacement
As many as one third of patients with swollen hemispheric supratentorial infarcts will be severely
disabled and fully dependent on care even after decompressive craniectomy, whereas most patients with
cerebellar infarct will have acceptable functional outcomes after surgery
Seizure Control
Seizures occur in 2-23% of patients within the first days after ischemic stroke. These seizures are usually focal,
but they may be generalized. Although primary prophylaxis for poststroke seizures is not indicated, secondary
prevention of subsequent seizures with standard antiepileptic therapy is recommended. [3]
A fraction of patients who have experienced stroke develop chronic seizure disorders. Seizure disorders
secondary to ischemic stroke should be managed in the same manner as other seizure disorders that arise as
a result of neurologic injury.[3]
Acute Decompensation
In the case of the rapidly decompensating patient or the patient with deteriorating neurologic status,
reassessment of the ABCs as well as hemodynamics and reimaging are indicated. Many patients who develop
hemorrhagic transformation or progressive cerebral edema will demonstrate acute clinical decline. Rarely, a
patient may have escalation of symptoms secondary to increased size of the ischemic penumbra. Careful
observation for hemorrhagic transformation (especially in the first 24 hours postreperfusion) and cerebral
edema in patients with hemispheric or posterior fossa strokes in the first 24-36 hours is warranted.
Neuroprotective Agents
The rationale for the use of neuroprotective agents is that reducing the release of excitatory neurotransmitters
by neurons in the ischemic penumbra may enhance the survival or these neurons. Despite very promising
results in several animal studies, however, no single neuroprotective agent in ischemic stroke has as yet been
supported by randomized, placebo-controlled human studies. Nevertheless, substantial research is under way
evaluating different neuroprotective strategies.
Hypothermia is fast becoming the standard of care for the ongoing treatment of patients surviving cardiac arrest
from ventricular tachycardia or ventricular fibrillation. However, no major clinical study has demonstrated a role
for hypothermia in the early treatment of ischemic stroke. [3]
Stroke Prevention
Primary prevention refers to the treatment of individuals with no history of stroke. Measures may include the
use of platelet antiaggregants, statins, and exercise. The 2011 AHA/ASA guidelines for the primary prevention
of stroke emphasize the importance of lifestyle changes to reduce well-documented modifiable risk factors,
citing an 80% lower risk of a first stroke in people who follow a healthy lifestyle compared with those who do
not.[23]
Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may
include the use of platelet antiaggregants,[127]antihypertensives, statins,[128] and lifestyle interventions. A study by
the Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators concluded that in stroke patients who
have significant intracranial arterial stenosis, aspirin should be used in preference to warfarin for secondary
prevention.[129]
Smoking cessation, blood pressure control, diabetes control, a low-fat diet, weight loss, and regular exercise
should be encouraged as strongly as the medications described above. The 2011 AHA/ASA guidelines
recommend ED-based smoking cessation interventions, and consider it reasonable for EDs to screen patients
for hypertension and drug abuse.[23]
Written prescriptions for exercise and medications for smoking cessation (ie, nicotine patch, bupropion,
varenicline) increase the likelihood of success with these interventions. In addition, the 2011 AHA/ASA
guidelines for primary stroke prevention indicate that it is reasonable to avoid exposure to environmental
tobacco smoke, despite a lack of stroke-specific data.
Patients who have had a stroke or transient ischemic attack (TIA) should be screened for diabetes and
obesity
Patients should possibly be screened for sleep apnea
Patients should possibly undergo a nutritional assessment and be advised to follow a Mediterraneantype diet
Patients who have had a stroke of unknown cause should undergo long-term monitoring for atrial
fibrillation (AF)
The new oral anticoagulants dabigatran (class I, level of evidence [LOE] A), apixaban (class I, LOE B),
and rivaroxaban (class IIa, LOE B) are among the drugs recommended for patients with nonvalvular AF
Based on research results, the guidelines also recommend that, in patients without deep venous thrombosis
(DVT), a patent foramen ovale not be closed. In addition, because there is little data to suggest that niacin or
fibrate drugs, as a means to raise high-density lipoprotein (HDL) cholesterol, reduce secondary stroke risk, the
guidelines no longer recommend their use.
appears to be safe and effective in reducing stroke recurrence and other vascular events (ie, transient ischemic
attack [TIA], acute coronary syndrome, MI), in patients with acute ischemic stroke or TIA. [134] Dual therapy was
also associated with a nonsignificant trend toward increased major bleeding.
The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) showed that the
combination of aspirin and dipyridamole was preferable to aspirin alone as antithrombotic therapy for cerebral
ischemia of arterial origin.[135]In ESPRIT, secondary prevention was started within 6 months of a TIA or minor
stroke of presumed arterial origin.
The addition of extended-release dipyridamole to aspirin therapy appears to be equally safe and effective
whether started early or late after stroke. A German study in 543 patients found no significant difference in
disability at 90 days, regardless of whether dipyridamole was started within 24 hours of stroke or TIA onset or
after 7 days of aspirin monotherapy.[136]
In contrast, the Management of AtheroThrombosis with Clopidogrel in High-risk patients with recent transient
ischaemic attack or ischaemic stroke (MATCH) trial, which included 7599 patients, found that adding aspirin to
clopidogrel did not significantly reduce major vascular events. However, the risk of life-threatening or major
bleeding was increased by the addition of aspirin. [137]
Atrial fibrillation
Atrial fibrillation (AF) is a major risk factor for stroke. The 2011 AHA/ASA primary stroke prevention guideline
recommends that EDs screen for AF and assess patients for anticoagulation therapy if AF is found. [23]
In the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W), oral
anticoagulation with warfarin proved superior to clopidogrel plus aspirin for prevention of vascular events in
patients with AF who were at high risk of stroke. [138] The study was stopped early because of clear evidence of
superiority of oral anticoagulation therapy.
Interestingly, in ACTIVE W, the rate of vascular events was significantly higher in patients who switched from
warfarin to clopidogrel plus aspirin as a result of randomization than in patients who had been on warfarin
before study enrollment and remained on warfarin during the study. The benefit of anticoagulation therapy over
dual antiplatelet therapy was much more modest in patients who had not been on warfarin before study
initiation and were then randomized to warfarin.
The 2011 ACC Foundation (ACCF)/AHA/Heart Rhythm Society (HRS) AF guideline update states that the new
anticoagulant dabigatran is useful as an alternative to warfarin in patients with AF who do not have a prosthetic
heart valve or hemodynamically significant valve disease.[139] However, a 2012 meta-analysis found an
increased risk for MI or acute coronary syndrome with dabigatran. [140]
For patients with AF after stroke or TIA, the 2010 AHA/ASA secondary stroke prevention guidelines are in
accord with the standard recommendation of warfarin, with aspirin as an alternative for patients who cannot
take oral anticoagulants. However, clopidogrel should not be used in combination with aspirin for such patients,
because the bleeding risk of the combination is comparable to that of warfarin. The guideline states that the
benefit of warfarin after stroke or TIA in patients without AF has not been established. [141]
PSC: Designed to maximize the timely provision of stroke-specific therapy, including the administration
of rt-PA; the center is also capable of providing care to patients with uncomplicated stroke
CSC: Shares the commitment that the PSC has to acute delivery of rt-PA and also provides care to
patients with hemorrhagic stroke and intracranial hemorrhage, as well as to all patients with stroke who
require emergent advanced imaging, intra-arterial therapies, neurosurgical interventions, and management in
a neurosurgical intensive care unit (NSICU)
PSCs and CSCs work most effectively when integrated into a regional stroke system of care so that patients
are treated at the most appropriate hospital based on factors such as severity, comorbidities, and timing.
Integrating regional prehospital services (911 and EMS) into this system of care ensures the most appropriate
triage from the field.
Additionally, stroke centers should have personnel versed in the monitoring of stroke vital signs, which include
the following:
Blood pressure
Glucose levels
Temperature
Oxygenation
Change in neurologic status
A further tier, acute stroke ready hospitals, is being defined as hospitals in which most of the necessary
resources are in place to emergently evaluate patients and potentially treat them with fibrinolytics, with the
assistance of remote stroke expertise, typically by telemedicine. Key to the optimal function of these stroke
centers is their interactions within a regional stroke system of care.
Coordination of care
Once patients have been identified as potential stroke patients, their ED evaluation must be fast-tracked to
allow for the completion of required laboratory tests and requisite noncontrast head CT scanning, as well as for
the notification and involvement of neurologic consultants. These requirements have led to the development of
"code stroke" protocols for the ED. In addition, EMS personnel are trained to identify possible stroke patients
and arrange for their speedy, preferential transport to a PSC or CSC. [80]
Hospitals with specialized stroke teams have demonstrated significantly increased rates of fibrinolytic
administration and decreased mortality. Cumulatively, the center should identify performance measures and
include mechanisms for evaluating the effectiveness of the system, as well as its component parts. The acute
care of the stroke patient is more than anything a systems-based team approach requiring the cooperation of
the ED, radiology, pharmacy, neurology, and intensive care unit (ICU) staff.
A stroke system should ensure effective interaction and collaboration among the agencies, services, and
people involved in providing prevention and the timely identification, triage to the most appropriate hospital,
rapid transport, treatment, and rehabilitation of stroke patients. For more information, see Stroke Team Creation
and Primary Stroke Center Certification.
Consultations
A stroke team or an experienced professional who is sufficiently familiar with stroke should be available within
15 minutes of the patient's arrival in the ED. Other consultations are tailored to individual patient needs. Often,
occupational therapy, physical therapy, speech therapy, and physical medicine and rehabilitation experts are
consulted within the first day of hospitalization.
Consultation of cardiology, vascular surgery, or neurosurgery may be warranted based on the results of carotid
duplex scanning , neuroimaging, transthoracic and transesophageal echocardiography, and clinical course.
During hospitalization, additional useful consultations include the following:
Medication Summary
While only 1 drug, recombinant tissue-type plasminogen activator (rt-PA), has demonstrated efficacy and
effectiveness in treating acute ischemic stroke and is approved by the FDA, other medications are equally
important. National consensus panels have included the use of antihypertensives, anticonvulsants, and osmotic
agents in their recommendations. Additional agents may be required for comorbid illnesses in many patients
with stroke.
Medications for the management of ischemic stroke can be distributed into the following categories:
Anticoagulation
Reperfusion
Antiplatelet
Neuroprotective
Thrombolytics
Class Summary
Thrombolyticmore accurately, fibrinolyticagents convert entrapped plasminogen to plasmin and initiate
local fibrinolysis by binding to fibrin in a clot.
View full drug information
Alteplase (Activase)
Alteplase is a t-PA used in management of acute myocardial infarction (MI), acute ischemic stroke, and
pulmonary embolism. Safety and efficacy with concomitant administration of heparin or aspirin during the first
24 hours after symptom onset have not been investigated.
Anticonvulsants, Other
Class Summary
While seizures associated with stroke are relatively uncommon, recurrent seizures may be life threatening.
Generally, agents used for treating recurrent convulsive seizures are also used in patients with seizures after
stroke. Benzodiazepines, typically diazepam and lorazepam, are the first-line drugs for ongoing seizures.
View full drug information
Diazepam (Valium)
Diazepam acts on the gamma-aminobutyric acid (GABA) receptor complex in the limbic system and thalamus,
producing a calming effect. The drug is useful in controlling active seizures and should be augmented by
longer-acting anticonvulsants, such as phenytoin or phenobarbital.
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Lorazepam (Ativan)
Lorazepam is a short-acting benzodiazepine with a moderately long half-life. It has become the drug of choice
in many centers for treating active seizures.
Antiplatelet Agents
Class Summary
Although antiplatelet agents have proved useful for preventing recurrent stroke or stroke after transient
ischemic attacks (TIAs), efficacy in the treatment of acute ischemic stroke has not been demonstrated. Early
aspirin therapy is recommended within 48 hours of the onset of symptoms but should be delayed for at least 24
hours after rt-PA administration. Aspirin should not be considered as an alternative to intravenous fibrinolysis or
other therapies aimed at improving outcomes after stroke.
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Aspirin (ASA)
Aspirin blocks prostaglandin synthetase action, which in turn inhibits prostaglandin synthesis and prevents the
formation of platelet-aggregating thromboxane A2. It also acts on the hypothalamic heat-regulating center to
reduce fever.
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Clopidogrel (Plavix)
Clopidogrel inhibits platelet aggregation and is used for secondary stroke prevention. It is indicated for the
reduction of atherothrombotic events following a recent stroke.
Anticoagulants, Hematologic
Class Summary
Anticoagulants such as warfarin are used for secondary stroke prevention.
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Dabigatran (Pradaxa)
Dabigatran is a competitive, direct inhibitor of thrombin that can prevent thrombus development. This agent
inhibits free and clot-bound thrombin and thrombin-induced platelet aggregation. It may be used as an
alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal
to permanent atrial fibrillation and risk factors for stroke or systemic embolization.
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Rivaroxaban (Xarelto)
Rivaroxaban is a Factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in patients
with nonvalvular atrial fibrillation. The dose is adjusted according to estimated creatinine clearance.
Apixaban (Eliquis)
Apixaban is a factor Xa inhibitor that inhibits platelet activation by selectively and reversibly blocking the active
site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. It inhibits free and clot-bound
factor Xa and prothrombinase activity. Although this agent has no direct effect on platelet aggregation, it does
indirectly inhibit platelet aggregation induced by thrombin. Apixaban is indicated to reduce risk of stroke and
systemic embolism associated with nonvalvular atrial fibrillation.
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Edoxaban (Savaysa)
Edoxaban is a Factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in patients with
nonvalvular atrial fibrillation. A lower dose is needed with CrCl < 50 mL/min. Do not use with CrCL >95 mL/min.
In the ENGAGE AF-TIMI 48 study, patients with NVAF with CrCL >95 mL/min had an increased rate of ischemic
stroke with edoxaban 60 mg/day compared with patients treated with warfarin.
Analgesics, Other
Class Summary
Hyperthermia in acute stroke is potentially harmful and should be treated. Agents with potential bleeding risk
should be avoided, if possible.
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ACE Inhibitors
Class Summary
Angiotensin-converting enzyme (ACE) inhibitors prevent the conversion of angiotensin I to angiotensin II, a
potent vasoconstrictor, resulting in lower aldosterone secretion.
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Enalapril (Vasotec)
An ACE inhibitor, enalapril decreases circulating angiotensin II levels and suppresses the renin-angiotensinaldosterone system, lowering overall blood pressure.
Optimal blood pressure management in acute stroke remains subject to some debate. Treatment parameters
depend largely on whether the patient is a candidate for fibrinolytic therapy. While the target blood pressures
may differ, the therapeutic agents are largely the same.
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Nicardipine (Cardene)
A calcium channel blocker, nicardipine inhibits calcium ion influx into vascular smooth muscle and myocardium.
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Vasodilators
Class Summary
Vasodilators lower blood pressure through direct vasodilation and relaxation of the vascular smooth muscle.
They are used more for blood pressure lowering in severe or refractory situations and should be used with
caution.
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