A c u t e Is c h e m i c St ro k e

a, b
Matthew S. West, MD *, Ethan U. Cumbler, MD

KEYWORDS
 Ischemic stroke  Evaluation  Management
 Secondary prevention

HOSPITAL MEDICINE CLINICS CHECKLIST

1. Identify patients with suspected acute ischemic stroke rapidly based on history,
risk factors, and clinical presentation.
2. Perform a concise neurologic examination to localize and characterize the
severity of deficits. A focused stroke scale examination such as the National
Institutes of Health Stroke Scale should be used.
3. Always obtain emergent brain imaging, most often a noncontrast computed
tomography scan of the head, as part of the initial evaluation. Intracranial
hemorrhage must be ruled out before initiation of therapy for acute ischemic
stroke.
4. All patients should have a complete blood count, glucose, creatinine,
prothrombin time/international normalized ratio, partial thromboplastin time,
troponin, and electrocardiogram during the initial evaluation.
5. Identify those patients who fulfill indications and have no contraindications, and
treat them as quickly as possible with intravenous thrombolysis if symptom
onset is within 4.5 hours. Delay in treatment is associated with worsened
outcome.
6. All ischemic stroke patients should undergo an evaluation for stroke etiology.
7. Begin to identify risk factors and initiate therapy for secondary prevention of
stroke while the patient is being treated in the hospital.
8. Educate all patients about the diagnosis of stroke and ways to mitigate their
individual risk factors.

a
Department of Neurology and Medicine, University of Colorado Hospital, University of
Colorado School of Medicine, 12401 East 17th Avenue, Mail Stop F782, Aurora, CO 80045, USA
b
Department of Medicine, Hospital Medicine Section, University of Colorado Hospital, University
of Colorado School of Medicine, Aurora, CO, USA
* Corresponding author.
E-mail address: matthew.west@ucdenver.edu

Hosp Med Clin 1 (2012) e223–e237

doi:10.1016/j.ehmc.2012.03.009
2211-5943/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.
e224 West & Cumbler

DEFINITIONS AND EPIDEMIOLOGY

1. How are transient ischemic attack and stroke defined and classified?

Transient ischemic attack (TIA) is characterized by the presence of focal neurologic

signs or symptoms lasting less than 24 hours. Pathologically there is focal brain, spinal
cord, or retinal ischemia without evidence of acute infarction. Ischemic stroke is
defined as evidence of pathologic infarction, with focal neurologic symptoms or signs
lasting more than 24 hours.1
Stroke is typically classified into 2 broad categories, namely ischemic and hemor-
rhagic, with subdivisions.
 Ischemic stroke is categorized into 5 subtypes based on major underlying
mechanisms.
 Large-artery atherosclerosis
 Cardioembolism
 Small-vessel occlusion
 Stroke of other determined cause (eg, hypercoagulable states and nonathero-
sclerotic vasculopathies)
 Stroke of undetermined cause
 Hemorrhagic stroke includes 2 main subtypes.
 Intraparenchymal hemorrhage (IPH)
 Subarachnoid hemorrhage (SAH).
Of all strokes approximately 87% are ischemic, 10% IPH, and 3% SAH.2

2. What are the prevalence, incidence, and societal burden of ischemic stroke in the
United States?

In the United States 795,000 people have a new or recurrent stroke each year, of
which 77% are considered first-time events. Approximately 55,000 more women
than men will have a stroke and blacks have an almost doubled risk of first-ever
strokes compared with whites. The overall stroke prevalence for individuals 20 years
and older is estimated to be 3%.3
Strokes account for 1 out of every 18 deaths in the United States, with blacks having
the highest age-adjusted death rates from stroke.
The estimated 30-day cost of stroke is $13,019 for mild ischemic stroke and
$20,346 for more severe strokes.3 Estimates of overall direct and indirect costs
from stroke in the United States are approximately $41 billion per year, with two-
thirds reflecting direct cost of care and the remainder indirect costs such as loss of
productivity.3

3. What are the major risk factors for stroke?

Risk factors can be divided into nonmodifiable and modifiable risk factors (Box 1).
The presence of atherosclerotic disease in any vascular bed increases the risk of
future stroke. Peripheral vascular disease, coronary heart disease, and especially prior
TIA are predictors of stroke risk, and merit intervention targeted at modifiable risk
factors.

4. What is the pathophysiology of stroke?

Ischemic strokes are the result of a reduction or cessation of blood flow to part of the
brain, often as a result of thrombus or embolus. The amount of vascular compromise is
 Acute Ischemic Stroke e225

Box 1
Risk factors for stroke

Nonmodifiable
 Age
 Gender
 Ethnicity/race
 Family history/genetics
Modifiable
 TIA
 Heart failure
 Hypertension
 Diabetes mellitus
 Atrial fibrillation
 Carotid stenosis
 Cerebrovascular dissection
 Dyslipidemia
 Tobacco use
 Obesity
 Physical Inactivity
 Heavy alcohol consumption
 Sickle cell disease
 Hypercoagulable states

an evolving process during an ischemic stroke that is related to the duration of

ischemia and degree of collateral circulation.
The brain receives approximately 20% of cardiac output, and normal cerebral blood
flow (CBF) is around 60 mL or 100 g per minute.4 Cerebral autoregulation maintains
CBF at a relatively constant rate by changes in vascular resistance. In response to
decreasing oxygen delivery during an ischemic stroke, autoregulation leads to local
vasodilation that increases blood flow and oxygen delivery, with the affected area
increasing oxygen extraction from the blood. Once these compensatory mechanisms
are overwhelmed, local perfusion pressure decreases and ischemia occurs.4
It is generally agreed that there can be an oligemic zone surrounding the core
infarct. This zone is termed the ischemic penumbra, and is where cerebral autoregu-
lation is disrupted and blood flow does not meet metabolic demands but where energy
metabolism is still preserved. The penumbra is viable tissue that is at risk yet can be
saved when reperfusion occurs in a timely manner.

HISTORY AND EXAMINATION

5. What are the most important factors to consider during the initial evaluation of acute
ischemic stroke?

The initial evaluation in patients with suspected stroke is to determine whether their
signs and symptoms are attributable to cerebral ischemia or another cause. Assess
e226 West & Cumbler

what neurologic deficits are present and if these deficits are focal, lateralizing, and/or
suggestive of hemispheric or brainstem injury, such as aphasia, hemiplegia, hemisen-
sory loss, or cranial nerve deficits. Deficits caused by an ischemic stroke can often be
localized to a specific vascular territory. Furthermore, historical data such as a sudden
onset of symptoms (rather than gradual, progressive symptoms) and significant risk
factors for stroke may all support the diagnosis.
When evaluating a patient with suspected acute stroke, one of the most important
details is the time of onset or, if not known, when the patient was last known to be at
baseline or symptom free. Establishing this timeframe is a critical for determining
whether a patient is a candidate for thrombolysis. Other important details include
severity of symptoms and whether symptoms are improving or resolving, as these
factors will also affect treatment decisions.
Evaluation should always consider clinical conditions that can mimic symptoms.
Some stroke mimics are listed in Box 2.

6. What is a focused stroke examination?

The goal of the bedside assessment in the acute setting is to be brief but thorough.
Airway, breathing, and circulation should be addressed in all patients, and a complete
set of vital signs, including weight, should be obtained.
A standardized stroke scale should be used to guide a rapid and focused neurologic
examination, thus ensuring that critical parts of the examination are performed and
can help facilitate communication between health care providers. The National Insti-
tutes of Health Stroke Scale (NIHSS) is a 15-item scale that is commonly used in
the evaluation of suspected stroke patients, and can be used reliably by both neurol-
ogists and nonneurologists.5 The NIHSS scores on a range from 0 (no deficits) to 42
(severe disability) based on the level of consciousness, orientation, response to
commands, gaze, visual fields, facial and extremity strength, coordination, sensation,
language, and speech. In addition, the NIHSS may be predictive of large-artery occlu-
sions, and aid in prognostication of neurologic outcomes.6
A complete evaluation should also include focused cardiac, respiratory, abdominal,
skin, and extremity examinations to identify underlying comorbidities and systemic
disease.

Box 2
Common stroke mimics and features

Seizure: History of seizures or postictal focal symptoms, postictal confusion. Witnessed seizure
activity does not rule out infarct, as up to 6% of stroke patients may have seizure at onset
Complicated migraine: History of migraines, migraine headache with symptoms, positive
symptoms (aura), history of similar prior events
Hypoglycemia: Depressed consciousness, history of diabetes treatment with hypoglycemic
medication, low serum glucose
Conversion disorder: Presentation and findings not consistent with vascular distribution,
inconsistent examination, comorbid psychiatric diagnosis
Toxic-metabolic encephalopathy: Altered mental status with absence of lateralizing signs and
symptoms
Space-occupying lesions: Often slower progression of focal symptoms. Headache may be
prominent
 Acute Ischemic Stroke e227

EVALUATION AND DIAGNOSIS

7. What imaging is most appropriate in evaluating a stroke patient?

Emergent brain imaging in suspected acute stroke should be performed in all cases
and can be used to exclude intracranial hemorrhage, evaluate for possible stroke
mimics such as a space-occupying lesion (see Box 2), evaluate for early ischemic
changes, and potentially identify targets for acute therapy. The most common imaging
techniques are:
 Noncontrast head computed tomography (CT). This method is recommended as
the initial diagnostic imaging modality in the emergent setting because it is readily
available, prompt, and sensitive for the detection of intracranial hemorrhage. In
some cases, early ischemic changes may be evident, such as loss of gray-
white differentiation and sulcal effacement suggestive of edema. Detection of
early ischemic changes on CT may be difficult, however, and a systematic review
found a sensitivity of 66% and specificity of 87%, both of which increased with
more experienced readers.7
 Multimodal advanced CT imaging. Some stroke imaging protocols include CT
angiography (CTA) and CT perfusion (CTP). CTA is a rapid and noninvasive tool
for assessment of the circulation for evidence of stenosis, occlusion, dissection,
and evaluation of the aortic arch. CTP uses flow of an iodine contrast bolus to
provide an approximate blood volume and transit time of blood to areas of the
brain. Evidence of mismatch between transit time and blood volume suggests
potentially reversible ischemia and salvageable brain parenchyma. CTP is limited
to only 2 to 4 brain slices and may miss smaller infarcts. Further disadvantages to
advanced CT imaging include additional time for evaluation, use of iodine
contrast, and additional radiation exposure.
 Brain magnetic resonance imaging (MRI). Compared with noncontrast CT
imaging, MRI with diffusion-weighted imaging (DWI) has higher accuracy in the
diagnosis of hyperacute stroke8; however, limited evidence suggests that
advanced CT imaging may be as sensitive.9 DWI allows detection of ischemic
areas within minutes of onset, and improves sensitivity for small areas of infarct
and ischemia in the posterior fossa. Multimodal MR sequences including MR
angiography (MRA) and perfusion-weighted imaging (PWI) are also available.
PWI uses paramagnetic contrast to approximate cerebral perfusion, and when
compared with DWI can help identify areas of hypoperfusion versus core infarct.
In a patient with a high clinical suspicion for stroke, thrombolysis should not be
delayed while awaiting advanced imaging studies, as a noncontrast head CT is
considered sufficient for treatment if indicated.

8. What laboratory tests should be ordered immediately for suspected ischemic stroke
patients?

Immediate laboratory/diagnostic tests are used to identify stroke mimics and deter-
mine if a patient is a candidate for intravenous thrombolysis. Recommended labora-
tory/diagnostic tests include:

 Complete blood count (CBC). Particular attention should be paid to the platelets
count, as values less than 100,000/mm3 are a contraindication to intravenous
thrombolysis.
 Basic metabolic panel, including serum glucose and creatinine.
e228 West & Cumbler

 Prothrombin time (PT)/international normalized ratio (INR)/activated partial throm-

boplastin time (aPTT). Coagulation studies are especially important in patients
known to be on warfarin or heparin. In the remainder of the population, one retro-
spective review found only 0.4% of patients had an unsuspected coagulopathy
that prevented thrombolysis.10
 Troponin. Elevated troponin levels are found in up to 18% of patients with
acute stroke.11 Although a subset of these patients may have an acute myocar-
dial infarction (AMI), in many instances an elevated troponin represents
transient neurogenic-induced cardiac injury. This injury may be caused by
increased sympathetic activity and catecholamine release resulting in suben-
docardial damage, transient left ventricular dysfunction, and a “stunned”
myocardium.12
 Electrocardiogram (ECG). ECGs are used to assess for AMI or cardiac arrhyth-
mias such as atrial fibrillation. Up to 75% to 90% of stroke patients have an
abnormal ECG, with the most common findings being repolarization abnormali-
ties, QT prolongation, T-wave abnormalities, and nonspecific ST changes.
Detection of atrial fibrillation on ECG in patients without prior history may occur
in up to 5% of patients with stroke, and can help guide further preventive
therapies.13

ACUTE MANAGEMENT

9. What are the indications, contraindications, and options for thrombolysis?

Patients treated with intravenous recombinant tissue plasminogen activator (IV rtPA)
are at least 30% more likely than those treated with supportive care to have minimal
or no disability at 3 months.14 IV rtPA is approved by the Food and Drug Administration
for treatment of ischemic stroke within 3 hours of symptom onset if patients satisfy
criteria shown in Box 3. Subsequent data have shown an increase in favorable
outcomes (52.4% vs 45.2%) when rtPA was used within 3 to 4.5 hours,15 leading to
an American Heart Association/American Stroke Association (AHA/ASA) endorsement
of use of IV rtPA in select eligible patients up to 4.5 hours after onset of symptoms.16
Although indicated up to 4.5 hours, treatment with IV rtPA should be given as soon
as possible, as subgroup analysis has shown the best odds for favorable outcome
occur when treatment is initiated within 90 minutes, with diminishing benefit over
time. In addition to IV rtPA, other acute treatment options include intra-arterial (IA)
thrombolysis or mechanical thrombolysis. There is evidence that IA thrombolysis
may be more beneficial for recanalization than intravenous thrombolysis in patients
with strokes secondary to large-artery occlusion.17
When IV rtPA is given, the recommended protocol is:
 0.9 mg/kg IV rtPA, with maximum dose 90 mg
 10% of total dose given as bolus over 1 minute, with remainder infused over 60
minutes
 During infusion, neurologic and blood pressure assessment every 15 minutes for
2 hours, then every 30 minutes for the next 6 hours and then hourly until 24 hours
after treatment
 Antiplatelet medications and anticoagulation should be held for 24 hours post-
rtPA
 No indwelling urinary catheters, nasogastric (NG) tubes, or arterial or central
venous catheters should be placed for 24 hours unless absolutely necessary.
 Acute Ischemic Stroke e229

Box 3
Inclusion and exclusion criteria for IV rtPA

Inclusion Criteria (adapted from NINDS IV rtPA)

Age older than 18 years
Diagnosis of ischemic stroke with measurable deficit
Time of onset less than 3 to 4.5 hoursa
CT without evidence of intracranial hemorrhage
Exclusion Criteria (adapted from NINDS IV rtPA)
Minor or rapidly resolving symptoms
Systolic blood pressure greater than 185 mm Hg or diastolic blood pressure greater than 110
mm Hg
Ischemic stroke or head trauma within 3 months
Symptoms suggestive of subarachnoid hemorrhage
Myocardial infarction within 3 months
GI or GU hemorrhage within 21 days
Major surgery within 14 days
Arterial puncture at noncompressible site within 7 days
History of previous intracranial hemorrhage
On anticoagulation with PT longer than 15 seconds or INR greater than 1.7
On heparin treatment with elevated aPTT
Platelet count less than 100,000/mm3
Serum glucose less than 50 mg/dL or greater than 400 mg/dL
Additional ECASS III exclusion for 3 to 4.5 hours
Age older than 80 years
Anticoagulation regardless of INRb
NIHSS >25
Previous stroke and history of diabetes
a
NINDS favors less than 3 hours, ECASS III suggests benefit if rtPA is given within 4.5 hours.13,14
b
Anticoagulation does not refer to antiplatelet therapy or prophylactic-dose heparin
products.
Abbreviations: ECASS, European Cooperative Acute Stroke Study; GI, gastrointestinal; GU,
genitourinary; IV rtPA, intravenous recombinant tissue plasminogen activator; NIHSS, National
Institutes of Health Stroke Scale; NINDS, National Institute of Neurological Disorders and
Stroke.

10. What are the risks and complications of intravenous thrombolysis?

The most well-known, and feared, risk of IV rtPA is symptomatic intracranial hemorrhage
(ICH). In the NINDS trial, symptomatic ICH occurred in 6.4% of rtPA-treated patients
versus 0.6% placebo patients within 36 hours of treatment.14 Risks for hemorrhage
may include advanced age, male gender, hyperglycemia (>200 mg/dL), and elevation
of blood pressure both pretreatment and posttreatment for 24 hours.18 The risk of
systemic hemorrhage is estimated at 1.6% and may be higher if there is deviation
from recommended treatment criteria.14 Orolingual angioedema has also been
e230 West & Cumbler

described as a side effect in up to 5% of patients, with increased risk if the patient is also
receiving an angiotensin-converting enzyme (ACE) inhibitor (relative risk of 13.6).19
11. What acute management is needed to ensure optimal outcomes and reduce
complications during hospitalization for acute ischemic stroke?
 Blood pressure control
 If IV rtPA is given, or going to be given, blood pressure must be less than 185
mm Hg systolic and less than 110 mm Hg diastolic and should be maintained
below 180/105 mm Hg for at least 24 hours after treatment. Recommended
medications to reach this goal include intravenous labetalol or a nicardipine
continuous intravenous infusion. Other short-acting medications such as intra-
venous hydralazine, esmolol, and enalaprilat can also be used.
 If IV rtPA is not given, current consensus guidelines recommend treatment
when systolic blood pressure is greater than 220 mm Hg or diastolic pressure
greater than 120 mm Hg.20 Several studies have demonstrated that aggressive
lowering of blood pressure in the acute setting is not beneficial,21 and may lead
to clinical worsening and poorer long-term outcomes.22 Therefore, it is not rec-
ommended unless another indication, such as aortic dissection or AMI, is
present. If blood pressure reduction is needed, it should be lowered by no
more than 15% during the first 24 hours.
 Glucose management. Hyperglycemia is present in up to one-third of patients
with an acute stroke, and there is evidence that poorer outcomes are associated
with hyperglycemia immediately following a stroke.23 Ongoing studies may shed
light on the optimal management of hyperglycemia in the acute period, but for
now guidelines support treatment with insulin for serum glucose greater than
140 to 185 mg/dL.20
 Temperature. Fever has been associated with increased mortality and poor
outcomes in patients with acute stroke24; however, studies have not shown
improved outcomes when body temperature is lowered.25 Elevated tempera-
tures should be investigated for possible infectious causes, and patients should
be treated symptomatically with antipyretics such as acetaminophen as needed.
 Fluid and electrolytes. Dehydration has been associated with slower recovery
and risk of venous thromboembolism. Accordingly, ensuring adequate hydration
is important and maintenance intravenous fluids should be considered in all
patients. Intravenous fluids are particularly important in patients not capable of
adequate oral intake because of dysphagia or depressed mental status. Isotonic
fluids, such as normal saline, are recommended, and rates should be based on
patient factors such as age, size, and medical comorbidities. Electrolytes should
be monitored closely and repleted as necessary to prevent complications such
as arrhythmias.
 Deep vein thrombosis (DVT) prophylaxis. DVT and pulmonary embolism are major
complications of acute stroke, and the risk is particularly high among older and
immobilized patients. Multiple trials26 have demonstrated the benefits of subcu-
taneous heparin and low molecular weight heparin in DVT prophylaxis, and one
of these agents should be used in all nonambulatory patients without contraindi-
cations. External compression devices are less effective and should be used only
when anticoagulants are contraindicated. Graded compression stockings,
whether below the knee or thigh high, are often inadequate to prevent DVT in
poststroke patients, but for patients who cannot tolerate other forms of DVT
prophylaxis, there may be a slight advantage to thigh-high stockings over
below-the-knee stockings.27
 Acute Ischemic Stroke e231

 Infection. Urinary tract infections (UTIs) and aspiration pneumonia are the most
common infectious complications among ischemic stroke patients, and are
associated with increased risk of unfavorable outcomes. UTIs occur in up to
15% of poststroke patients and risk factors include catheterization, higher
disability, and older age.28 Early mobilization and limited use of indwelling cath-
eters may decrease the risk. Pneumonia occurs in 5% to 20% of patients, with
risk factors including age older than 65 years, dysarthria, cognitive impairment,
and abnormal water swallow test (which involves the patient drinking 3 ounces
of water during which time they are monitored for coughing or choking).29 All
patients with suspected stroke should have a bedside swallow evaluation per-
formed on presentation, and individuals thought to be at high risk for aspiration
should not be given anything by mouth until a formal swallow evaluation is
completed. If medications or nutrition is needed, an NG tube can be placed.

12. What is the basic workup for identifying the cause of a stroke?

 Vascular imaging. All patients with ischemic stroke should undergo neurovascu-
lar imaging to evaluate for atherosclerosis, stenosis amendable to intervention, or
vascular injury. First-line noninvasive tests include carotid duplex ultrasound,
CTA, and MRA. Carotid ultrasonography should only be used as a screening
test if an anterior circulation stroke has occurred, as this does not optimally visu-
alize the posterior circulation. If a vertebrobasilar distribution infarct is suspected,
the imaging of choice is CTA or MRA.
 Echocardiogram. Current AHA/ASA guidelines state that a transthoracic echocar-
diogram (TTE) is “reasonable” if no cause of TIA or stroke has been identified by
other workup.20 TTE with agitated saline is often performed first, as it is noninvasive
and low risk. Transesophageal echocardiogram (TEE), however, is more sensitive
in identifying a cardioembolic source. If there is high suspicion for a cardioembolic
stroke and the initial TTE is negative, a TEE should be considered because there is
increased yield in detection of abnormalities that may change management.30
 Telemetry. Telemetry should be used for monitoring of arrhythmias during hospi-
talization for acute stroke. Telemetry may double the yield of detection of atrial
fibrillation when used for 48 hours, compared with routine ECG.13
 Fasting lipids. A fasting lipid panel should be checked in all patients with stroke
because elevated low-density lipoprotein is a target for secondary prevention.
 Hemoglobin A1c (HgA1c). HgA1c has several advantages over a fasting glucose
measurement, as it reflects average glucose levels over the prior 2 to 3 months
and is not influenced by conditions such as stress-induced hyperglycemia. An
HgA1c level higher than 6.5% is diagnostic of diabetes and indicates another
target for secondary prevention of stroke.
 Hypercoagulability panel. Young patients with cryptogenic stroke, patients with
prior thrombotic events, or those with a suggestive family history should be as-
sessed for evidence of a thrombophilic condition.

LONG-TERM MANAGEMENT

13. What are the options for secondary prevention of stroke?

 Antiplatelet medications. For most patients with noncardioembolic stroke, anti-

platelet medications are the treatment of choice. Aspirin, clopidogrel, and aspirin
e232 West & Cumbler

plus extended-release dipyridamole are all beneficial in secondary prevention of

stroke (Box 4). The best medication is based on risk factors, cost, and tolerance.
 Anticoagulation. The use of anticoagulation for acute noncardioembolic ischemic
stroke is typically not indicated. A 2008 systematic review found that acute use of
anticoagulants in ischemic stroke did not reduce the odds of death or functional
dependence, but did increase the risk of symptomatic hemorrhage.37
 Studies have also found that warfarin is no more beneficial than aspirin in long-
term stroke prevention in noncardioembolic stroke, but is associated with higher
risk of adverse events.38 Anticoagulation is, however, the preferred choice for
cardioembolic stroke and reduces the risk of recurrent stroke by approximately
two-thirds in patients with atrial fibrillation. The clinical circumstances whereby
anticoagulation may be appropriate and should be considered are listed in Box 5.
Warfarin is the most commonly used long-term medication for these indications,
with a goal INR typically between 2 and 3. Dabigatran, an oral direct thrombin inhibitor,
is now approved for nonvalvular atrial fibrillation, and has been shown to have lower
rates of stroke with a similar rate of adverse events compared with warfarin.39 Addi-
tional anticoagulants inhibiting factor Xa, such as rivaroxaban and apixaban, have
been studied and found to be at least as effective as warfarin for stroke prevention
in atrial fibrillation, and may have lower bleeding risks.40,41
Additional risk factor modifications are shown in Box 6.

14. What treatment options are available for symptomatic and asymptomatic extracra-
nial carotid stenosis?
Carotid endarterectomy (CEA) and carotid artery angioplasty with stenting (CAS) are
both options for management of extracranial atherosclerotic stenosis, and reduce
the long-term risk of ischemic stroke. Carotid intervention is recommended for greater
than 70% stenosis on the ipsilateral side of the ischemic lesion. At 50% to 69%
stenosis, CEA can be considered based on age, gender, comorbidities, and individu-
alized assessment of risk.1 The magnitude of benefit rises with increasing degree of
stenosis up to chronic complete occlusion. Important considerations in selecting
patients for carotid intervention are life expectancy (patients with limited life span

Box 4
Antiplatelet medications

Aspirin31: 23% reduction in vascular events in meta-analysis. Recommended dosing is between

50 and 325 mg per day. Doses higher than 325 mg per day have not been shown to be more
beneficial than lower doses, but have higher adverse events
Clopidogrel: Recommended dose of 75 mg per day. Has a modest, but significant, 8.7% relative
risk reduction in stroke, myocardial infarction, and vascular death versus aspirin.32 No
significant difference in reduction of recurrent stroke when compared with aspirin plus
dipyridamole33
Aspirin plus extended-release dipyridamole: Significant 1% per year reduction in stroke,
myocardial infarction, and vascular death compared with aspirin alone.34 No significant
difference in reduction of recurrent stroke when compared with clopidogrel
Combination therapy: Not recommended for secondary stroke prevention alone. Combination
of clopidogrel and aspirin versus either agent alone35,36 has no significant risk reduction of
recurrent stroke, but does have increased risk of life-threatening bleeds
 Acute Ischemic Stroke e233

Box 5
Indications for use of anticoagulation after stroke

Atrial fibrillation
Hypercoagulable state (antiphospholipid antibodies)
Recent myocardial infarction with left ventricle thrombus
Mechanical heart valve
Extracranial arterial dissectiona
Aortic atherosclerosis with thrombusa
Cardiomyopathy with ejection fraction less than 35%a
a
Degree of benefit currently unclear.

may suffer the short-term risks of the procedure without living long enough to benefit
from long-term reduction in stroke rates) and operator complication rates (<6% is rec-
ommended). In general, CEA can be performed 2 to 6 weeks after a stroke, but TIAs
and minor strokes may have the most favorable outcomes when CEA is performed
earlier, within the first 2 weeks.1 Carotid intervention is not indicated for less than
50% stenosis on the symptomatic side or less than 60% stenosis on the asymptom-
atic side.
CAS may be preferred when the stenosis is difficult to access surgically, when
medical conditions (particularly cardiac) increase the risk for surgery, or for situations
such as radiation-induced stenosis or restenosis after CEA. Although studies have
conflicting results, a meta-analysis demonstrated that CAS has higher rates of peri-
procedural stroke but lower rates of myocardial infarction than CEA.42
Stenting of intracranial arteries has not been demonstrated to be more effective than
optimal medical therapy, and carries higher early risk of stroke.43

Box 6
Risk factors and recommendations

Hypertension: The recommended goal blood pressure is less than 140/90 mm Hg, or less than
130/80 mm Hg if diabetic or chronic kidney disease, as per Joint National Committee (JNC) 7
Optimal drug regimen is not known but diuretics or combination diuretic and ACE inhibitor has
been shown to be beneficial. Decision of which antihypertensive medication to use should be
individualized based on other comorbid illness
Dyslipidemia: Statin therapy should be initiated if low-density lipoprotein (LDL) level 100 mg/dL
or more, and a target reduction should be at least a 50% decrease or less than 70 mg/dL.
Diabetes: Goal HgA1c less than 7%
Tobacco use: Tobacco cessation should be advised in all patients who have smoked in the last
year. Resources, counseling, and pharmacologic aids to cessation are associated with higher
smoking quit rates
Exercise: 30 minutes of moderate-intensity exercise is recommended 1 to 3 times per week
Alcohol use: No more than 2 drinks per day for men and 1 drink per day for women. Heavier
alcohol use is associated with increased stroke risk and should be discouraged
e234 West & Cumbler

OUTCOMES

15. What degree of recovery in neurologic function is expected after stroke?

Prediction of recovery after stroke is difficult because there are multiple factors such
as age, medical comorbidities, severity of initial disability, and medical complications
that may contribute to the ability to regain prior level of function. Based on the original
NINDS trial, patients treated with rtPA had at least a 30% better chance of having
minimal or no disability at 3 months.14
One consistent predictive factor for recovery is the initial severity of impairment of
function. The NIHSS has been shown to predict short-term and long-term outcomes,
with each additional point on the scale decreasing the likelihood of excellent outcome
at 3 months by 17%.6
The timing of recovery also varies, but typically the most improvement is observed
within the first 3 months, and it is a poor prognostic sign if there is no improvement of
motor function by 6 months. A critical component to attaining recovery after stroke is
early initiation of rehabilitation. Improvements have been noted with a variety of inter-
ventions including constraint-induced movement therapy, physical fitness training,
physiotherapy, and repetitive task training.44

16. What should poststroke counseling of patients include?

Providing education to the patient and the patient’s family is an important part of
stroke care. All patients should receive poststroke counseling including:

 Review patient-specific risk factors for stroke and strategies to address them,
such as lifestyle modifications including exercise, tobacco cessation, and adher-
ence to prescribed medications
 Understand medications prescribed at discharge, their indication, and what
medications have been added, changed, or discontinued
 Reinforce the need for consistent follow-up with a practitioner with stroke exper-
tise after discharge
 Identify warning signs and symptoms of recurrent stroke
 Recognize the importance of early activation of the emergency medical system
if stroke signs or symptoms arise.

GUIDELINES AND STATEMENTS

17. What quality measures are tracked for hospital stroke care?
The Joint Commission, aligned with Centers for Medicare and Medicaid services,
implemented core quality measures for ischemic stroke in 2009. The acute stroke
core measures are:

 Started on DVT prophylaxis by end of hospital day 2

 Discharged on antithrombotic therapy
 Antithrombotic therapy started by the end of hospital day 2
 Anticoagulation therapy given for atrial fibrillation
 Thrombolytic therapy administered to eligible patient
 Discharged on a statin medication if LDL greater than 100 mg/dL
 Stroke education provided to patient
 Patient is assessed for rehabilitation needs.
 Acute Ischemic Stroke e235

18. Where can I find consensus guidelines for recommended stroke management?
 American Heart Association Web site. Statements/Guidelines: http://www.heart.
org
 Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early manage-
ment of adults with ischemic stroke: a guideline from the American Heart Asso-
ciation/American Stroke Association Stroke Council, Clinical Cardiology Council,
Cardiovascular Radiology and Intervention Council, and the Atherosclerotic
Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdis-
ciplinary Working Groups: the American Academy of Neurology affirms the value
of this guideline as an educational tool for neurologists. Stroke 2007;38:1655–
711.
 Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in
patients with stroke or transient ischemic attack: a guideline for healthcare
professionals from the American Heart Association/American Stroke Associa-
tion. Stroke 2011;42:227–76.
 NIH Stroke Scale: http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf

REFERENCES

1. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in
patients with stroke or TIA. Stroke 2011;42:227–76.
2. Incidence and prevalence: 2006 chart book on cardiovascular and lung
diseases. Bethesda (MD): National Heart, Lung, and Blood Institute; 2006.
3. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—
2011 update. Circulation 2011;123:e18–209.
4. Markus HS. Cerebral perfusion and stroke. J Neurol Neurosurg Psychiatry 2004;
75:353–61.
5. Goldstein LB, Samsa GP. Reliability of the National Institutes of Health Stroke
Scale: extension to non-neurologists in the context of a clinical trial. Stroke
1997;28:307–10.
6. Adams HP, Davis PH, Leira EC, et al. Baseline NIH Stroke Scale score strongly
predicts outcome after stroke. Neurology 1999;53(1):126–31.
7. Wardlaw JM, Mielke O. Early signs of brain infarction on CT: observer reliability
and outcome after thrombolytic treatment. Radiology 2005;235:444–53.
8. Fiebach JB, Schellinger PD, Jansen O, et al. CT and diffusion-weighted MR
imaging in randomized order. Stroke 2002;33:2206–10.
9. Schramm P, Schellinger PD, Klotz E. Comparison of perfusion CT and CT angiog-
raphy source images with perfusion-weighted imaging and diffusion-weighted
imaging in patients with acute stroke of less than 6 hours duration. Stroke
2004;35(7):1652–8.
10. Rost NS, Masrur S, Pervez MA. Unsuspected coagulopathy rarely prevents IV
thrombolysis in acute ischemic stroke. Neurology 2009;73(23):1957–62.
11. Kerr G, Ray G, Wu O. Elevated troponin after stroke: a systematic review. Cere-
brovasc Dis 2009;28(3):220–6.
12. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation
2008;118:397–409.
13. Ustrell X, Pellise A. Cardiac workup of ischemic stroke. Curr Cardiol Rev 2010;6:
175–83.
14. The NINDS rtPA Stroke Study Group. Tissue plasminogen activator for acute
ischemic stroke. N Engl J Med 1995;333:1581–8.
e236 West & Cumbler

15. Hacke W, Kaste M, Bluhmki E. Thrombolysis with alteplase 3 to 4.5 hours after
acute ischemic stroke. N Engl J Med 2008;359:1317–29.
16. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treat-
ment of acute ischemic stroke with intravenous tissue plasminogen activator.
Stroke 2009;40:2945–8.
17. Sen S, Huang DY, Akhavan O. IV vs. IA tPA in acute ischemic stroke with CT
angiographic evidence of major vessel occlusion: a feasibility study. Neurocrit
Care 2009;11(1):76–81.
18. Miller DJ, Simpson JR, Silver B. Safety of thrombolysis in acute ischemic stroke:
a review of complications, risk factors, and newer technologies. The Neurohospi-
talist 2011;1:138–47.
19. Hill MD, Lye T, Moss H, et al. Hemi-orolingual angioedema and ACE inhibition
after alteplase treatment of stroke. Neurology 2003;60(9):1525–7.
20. Adams HP, del Zoppo G, Alberts MJ, et al. Guidelines for the early management
of adults with ischemic stroke. Stroke 2007;38:1655–711.
21. Sandset EC, Bath PM, Boysen G. The angiotensin-receptor blocker candesartan
for treatment of acute stroke. Lancet 2011;377:741–50.
22. Castillo J, Leira R, Garcı́a MM, et al. Blood pressure decrease during the acute
phase of ischemic stroke is associated with brain injury and poor stroke outcome.
Stroke 2004;35:520–6.
23. Bruno A, Biller J, Adams HP. Acute blood glucose level and outcome from
ischemic stroke. Neurology 1999;52(2):280–4.
24. Greer DM, Funk SE, Reaven NL, et al. Impact of fever on outcome in patients with
stroke and neurologic injury. Stroke 2008;39:3029–35.
25. Den Hertog HM, van der Worp HB. Cooling therapy for acute stroke. Cochrane
Database Syst Rev 2009;1:CD001247.
26. Sandercock PA, Counsell C, Tseng MC. Low-molecular weight heparins or hepa-
rinoids versus standard UFH for acute ischaemic stroke. Cochrane Database
Syst Rev 2008;3:CD000119.
27. CLOTS Trial Collaboration. Thigh-high versus below-knee stockings for deep
venous thrombosis prophylaxis after stroke. Ann Intern Med 2010;153:553–62.
28. Stott DJ, Falconer A, Miller H, et al. Urinary tract infection after stroke. QJM 2009;
102:243–9.
29. Johnston KC, Li JY, Lyden PD, et al. Medical and neurological complications of
ischemic stroke. Stroke 1998;29(2):447–53.
30. Harloff A, Handke M, Reinhard M, et al. Therapeutic strategies after examination
by TEE in 503 patients with ischemic stroke. Stroke 2006;37:859–64.
31. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomized
trials of antiplatelet therapy for prevention of death, MI, and stroke in high risk
patients. BMJ 2002;324:71–86.
32. CAPRIE steering committee. A randomized, blinded, trial of clopidogrel versus
aspirin in patients at risk of ischemic events. Lancet 1996;348:1329–39.
33. Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyrida-
mole versus clopidogrel for recurrent stroke. N Engl J Med 2008;359:
1238–51.
34. ESPIRIT Study Group, Halkes PH, van Gijn J, et al. Aspirin plus dipyridamole
versus aspirin alone after cerebral ischemia of arterial origin (ESPRIT). Lancet
2006;367:1665–73.
35. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone
for the prevention of atherothrombotic events. N Engl J Med 2006;354:
1706–17.
 Acute Ischemic Stroke e237

36. Diener HC, Bogousslavsky J, Brass LM, et al. Clopidogrel and aspirin compared
with clopidogrel alone after recent ischemic stroke or TIA in high-risk patients
(MATCH). Lancet 2004;364:331–7.
37. Sandercock PA, Counsell C, Kamal AK. Anticoagulants for acute ischaemic
stroke. Cochrane Database Syst Rev 2008;4:CD000024.
38. Sandercock PA, Gibson LM, Liu M. Anticoagulants for preventing recurrence
following presumed non-cardioembolic ischaemic stroke or TIA. Cochrane Data-
base Syst Rev 2009;2:CD000248.
39. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients
with atrial fibrillation. N Engl J Med 2009;361:1139–51.
40. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular
atrial fibrillation. N Engl J Med 2011;365:883–91.
41. Granger CB, Alexander JH, Mcmurray J, et al. Apixaban versus warfarin in
patient with atrial fibrillation. N Engl J Med 2011;365:981–92.
42. Murad MH, Shahrour A, Shah ND, et al. A systematic review and meta-analysis of
randomized trials of carotid endarterectomy vs stenting. J Vasc Surg 2011;53:
792–7.
43. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical
therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993–1003.
44. Lanhorne P, Coupar F. Motor recovery after stroke: a systematic review. Lancet
Neurol 2009;8:741–54.