Approach Considerations

Imaging studies

Emergent brain imaging is essential for excluding mimics (SAH, ICH, masses) and
potentially 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. Multimodal CT imaging with the
addition of CT angiography and CT perfusion to NCCT has the potential to identify large vessel
occlusions and areas of salvagable tissue.

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
 Antinuclear antibody (ANA)
Rheumatoid factor
Homocysteine level
Rapid plasma reagent (RPR)

A urine pregnancy test should be obtained for all women of childbearing age with stroke
symptoms. The safety of the fibrinolytic agent recombinant tissue-type plasminogen activator (rt-
PA) in pregnancy has not been studied in humans (ie, the agent is in the FDA pregnancy category
C).

Brain Imaging With CT Scanning and MRI

CT scanning

Imaging with CT scanning has multiple logistic advantages for patients with acute stroke. Image
acquisition is faster with CT scanning than with MRI, allowing for assessment with an
examination that includes noncontrast CT scanning, CT angiography (CTA), and CT perfusion
scanning in a short amount of time. Expedient acquisition is of the utmost importance in acute
stroke imaging because of the narrow window of time available for definitive ischemic stroke
treatment with pharmacologic agents and mechanical devices.

CT scanning can also be performed in patients who are unable to tolerate an MR examination or
who have contraindications to MRI, including implantable pacemakers, some aneurysm clips, or
other ferromagnetic materials in their bodies. Additionally, CT scanning is more easily accessible
and commonly located in the ED, which is helpful for patients who require special equipment for
monitoring or life support. [64, 65]

MRI

Previously, 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.) [1, 66, 67, 68]
 Magnetic resonance imaging (MRI)
scan in a 70-year-old woman with a history of left-sided weakness for several hours. An axial T2
fluid-attenuated inversion recovery (FLAIR) image (left) demonstrates high signal in the
lentiform nucleus with mass effect. The axial diffusion-weighted image (middle) demonstrates
high signal in the same area, with corresponding low signal on the apparent diffusion coefficient
(ADC) maps, consistent with true restricted diffusion and an acute infarction. Maximum
intensity projection from a 3-dimensional (3-D) time-of-flight magnetic resonance angiogram
(MRA, right) demonstrates occlusion of the distal middle cerebral artery (MCA) trunk (red
circle).
View Media Gallery

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.
View Media Gallery
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. [69]

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.

Other Imaging Studies in Ischemic Stroke

Transcranial Doppler ultrasonography is useful for evaluating more proximal vascular anatomy
including the middle cerebral artery (MCA), intracranial carotid artery, and vertebrobasilar
arterythrough the infratemporal fossa. [71] Echocardiography is obtained in all patients with
acute ischemic stroke in whom cardiogenic embolism is suspected.

Chest radiography has potential utility for patients with acute stroke. However, obtaining a chest
radiograph should not delay the administration of rt-PA, as radiographs have not been shown to
alter the clinical course or decision-making in most cases. [72]

The use of single-photon emission CT (SPECT) scanning in stroke is still experimental and is
available only at select institutions. Theoretically, it can define areas of altered regional blood
flow. [73]

Conventional angiography is the gold standard in evaluating for cerebrovascular disease as well
as for disease involving the aortic arch and great vessels in the neck. Conventional angiography
can be performed to clarify equivocal findings or to confirm and treat disease seen on MRA,
CTA, transcranial Doppler, or ultrasonography of the neck. (See the images below.)
 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).
View Media Gallery
 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).
View Media Gallery

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).
View Media Gallery
 Image on the left demonstrates
deployment of a clot retrieval device (older generation device) in a 31-year-old man. Followup
angiogram after embolectomy demonstrates recanalization of the distal basilar artery with filling
of the superior cerebellar arteries and posterior cerebral arteries. The patient had complete
resolution of symptoms following embolectomy (images courtesy of Concentric Medical).
View Media Gallery

Blood Studies
A CBC serves as a baseline study and may reveal a cause for the stroke (eg, polycythemia,
thrombocytosis, thrombocytopenia, leukemia), identify evidence of concurrent illness (eg,
anemia), or issues that may affect reperfusion strategies (thrombocytopenia). 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 or to identify
sympathomemetic (cocaine) use, which may be the cause of the ischemic or hemorrhagic stroke .
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 clinical outcomes in
ischemic stroke.

Palliative care

Palliative care is an important component of comprehensive stroke care. Some patients with
severe strokes die during the initial hospitalization, others will be severely disabled and
palliative care can begin to address the patient's and family's short- and long-term needs. 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.

Acute Management of Stroke

The goal for the emergent management of stroke is to assess the patients airway, breathing, and
circulation (ABCs); stabilize the patient as necessary; and complete initial evaluation and
assessment, including imaging and laboratory studies, within 60 minutes of patient arrival. [1] A
Finnish study demonstrated that time to treatment with fibrinolytics can be decreased with
changes in EMS and ED coordination and in ED procedures for treating acute stroke patients. [78]

A US study in which a multidisciplinary team used value stream analysis to assess the steps
required to treat acute ischemic stroke with IV rt-PA found several inefficiencies in the protocol
(eg, in patient routing) that were slowing treatment. Use of a revised protocol that targeted those
inefficiencies reduced door-to-needle times from 60 to 39 minutes and increased the percentage
of patients treated in 60 minutes or less after hospital arrival from 52% to 78%, with no change
in symptomatic hemorrhage rate. [79]
Critical decisions focus on the need for airway management, establishment of optimal blood
pressure control, and identification of potential reperfusion therapies (IV fibrinolysis with rt-PA
or intra-arterial approaches). Involvement of a physician with stroke expertise is ideal. Stroke
care units with specially trained personnel exist and improve outcomes.

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.

Hypoglycemia and hyperglycemia

Hypoglycemia needs to be identified and treated early in the evaluation. In contrast, the
management of hyperglycemia in acute stroke remains an area of uncertainty. [80] Extreme
hyperglycemia is detrimental in the setting of acute stroke.

Hyperglycemia is common after acute ischemic stroke, even in patients without diabetes. A
Cochrane review found that the use of IV insulin to maintain serum glucose in the range of 4-7.5
mmol/L (72-135 mg/dL) in the first 24 hours of ischemic stroke did not improve functional
outcome, death rates, or final neurologic deficit and significantly increased the risk of
hypoglycemia.

Stroke Prevention
Primary prevention refers to the management of individuals with no history of stroke.
Preventative measures may include the use of antiplatelet agents, statins, smoking cessation 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. [22]

Secondary prevention refers to the treatment of individuals who have already had a stroke.
Measures may include the use of anitplatelet agents, [128] anticoagulants (warfarin or newer novel
oral anticoagulants) antihypertensives, statins, [129] 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. [130]
Smoking cessation, blood pressure control, diabetes control, a low-fat low-salt 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. [22]

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.

Aspirin for primary prevention

Overall, the value of aspirin in primary prevention appears uncertain, [131] and its use for this
purpose is not recommended for patients at low risk. Aspirin is recommended for primary
prevention only in persons with at least a 6-10% risk of cardiovascular events over 10 years. [22]

On the other hand, low-dose aspirin may be beneficial for primary prevention of stroke in
women. A randomized, placebo-controlled trial in 39,876 initially healthy women aged 45 years
or older demonstrated that 100 mg of aspirin on alternate days resulted in a 24% reduction in the
risk of ischemic stroke, with a nonsignificant increase in the risk of hemorrhagic stroke. [132]

Secondary prevention guidelines

Guidelines issued in 2014 by the American Heart Association (AHA)/American Stroke

Association (ASA) on the secondary prevention of stroke emphasize nutrition and lifestyle and
include a new section on aortic atherosclerosis. New recommendations include the following [133,
134]
:

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
Mediterranean-type 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.
Dual antiplatelet therapy for secondary prevention

A systematic review and meta-analysis of 12 randomized trials involving 3766 patients

concluded that, compared with aspirin alone, dual antiplatelet therapy with aspirin plus either
dipyridamole or clopidogrel 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. [135] 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. [136] 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. [137]

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. [138]

Carotid artery stenosis

For patients at risk for stroke from asymptomatic carotid artery stenosis, the 2011 AHA/ASA
primary prevention guidelines state that older studies that showed revascularization surgery as
more beneficial than medical treatment may now be obsolete because of improvements in
medical therapies. Therefore, individual patient comorbidities, life expectancy, and preferences
should determine whether medical treatment alone or carotid revascularization is selected. [22]

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. [22]

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. [139] 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. [140]
However, a 2012 meta-analysis found an increased risk for MI or acute coronary syndrome with
dabigatran. [141] With the advent of other novel anticoagulants, the American Academy of
Neurology produced guidelines for the prevention of stroke in nonvalvuar atrial fibrillation in
2014. [156] The guidelines recommend that clinicians should administer dabigatran, rivaroxaban, or
apixaban to patients who have nonvalvular atrial fibrillation requiring anticoagulant medication
and are at higher risk of intracranial bleeding; they also suggest that clinicians might offer
apixaban to patients with nonvalvular atrial fibrillation and GI bleeding risk who require
anticoagulant medication.

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.