Ischemic Stroke

Shahzad Khan, MD
 Ischemic Stroke

 Cerebrovascular disease is the third leading cause

of death in developed countries after heart disease
and cancer
 In the United States, someone experiences a
stroke every 45 seconds, and someone dies of a
stroke every 3 minutes ( American Heart Association.
Heart disease and stroke statistics--2004 update. Accessed Nov 2, 2004)

 About 15% to 20% of strokes are preceded by a

TIA
 TRANSIENT ISCHEMIC ATTACK

 Definition: TIA is the sudden onset of a

focal neurologic deficit that lasts less than
24 hours

 Transient decrease in blood supply

Proposed "tissue-based” definition
of TIA
 “A brief episode of
neurologic
dysfunction caused
by focal brain or
retinal ischemia, with
clinical symptoms
typically lasting less
than one hour, and
without evidence of
acute infarction"
 Stroke

 Stroke is the acute neurologic injury which

occurs as a result brain ischemia or
hemorrhage

 Approximately 80 percent of strokes are

due to ischemic cerebral infarction and 20
percent to brain hemorrhage
 Stroke
 An infarcted brain is
pale initially.

 Within hours to days,

the gray matter
becomes congested
with engorged, dilated
blood vessels and
minute petechial
hemorrhages
 Stroke
 An embolus blocking
a major vessel can
migrates or lyses

 Recirculation into the

infarcted area can
cause a hemorrhagic
infarction and may
aggravate edema
formation.
Diagnostic Evaluation of Cerebral Infarction
or TIA

 Goals
 determine a potential mechanism requiring
prevention other than an antiplatelet agent

 identify and treat contributing risk factors

 complete the evaluation in a cost-effective

and safe manner
 Systematic Approach to Diagnostic
Evaluation of Cerebral Infarction or TIA

 1. Are the symptoms consistent with a

cerebral infarction or TIA?

 Focal seizures and migraine equivalents

Both are more commonly associated with positive
phenomena (gain of function such as flashing
lights or paresthesias, shaking limb)

• Hypoglycemia.
 2. Where does the ischemic
event localize?

 Ischemic event in the anterior or posterior

(vertebrobasilar) circulation

 Ischemic event cortical or subcortical

 Cortical  Sub-cortical
 Aphasia  Face, arm and leg
 Visual field defect more equally affected
 Hemi or monoparasis  Lacunar syndrome
• Pure motor
 Cortical sensory loss
• Pure sensory
 hemineglect • Ataxic hemiparasis
• Clumpsy-hand
dysarthia
• sensorymotor
 3. What etiologies and mechanisms of
cerebral infarction and TIA are possible?
 4. What is the prevalence of
each potential etiology?
 cardioembolic (27%)
 large-vessel disease (18%)
 small-vessel disease (17%)
 other (3%), and
 cryptogenic (35%) ( other studies 15-35%)

 Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O'Fallon WM,
Wiebers DO. Ischemic stroke subtypes: a population-based study of
incidence and risk factors. Stroke. 1999;30:2513-2516.
5. What treatments are available
for this etiology?

 For most mechanisms of cerebral

infarction or TIA, antiplatelet agents are
indicated

 Therefore, diagnostic evaluation is aimed

at evaluating potential mechanisms that
would require something other than an
antiplatelet agent
 A 76 year old male develop numbness and
weakness of right side and found to have
Lt. MCA stroke. His evaluation showed no
carotid stenosis or cardioembolic source.
He has history of HTN, Hyperlipidemia.
His medicine includes ECASA 325 mg,
Lipitor and lisinopril. Which is the next
reasonable step?
 A. ASA 1300 mg/day
 B. ASA 325 plus Plavix (Clopidogrel)
 C. ASA 25 mg plus 200 mg ER dipyridamole
 D. ASA 25 mg plus IR 75 dipyridamole
 E. Warfarin.
 Recurrent stroke prevention
Study ARR NNT
CAPRIE 0.8% 125
TASS 2.5% 40
ESPS 2 3.0% 33
6. What tests and studies are
useful to evaluate this
etiology?
 Cardioembolic Source
 20% to 30% of cerebral infarctions are a
result of a cardioembolic source.
 Atrial fibrillation is more common in
persons older than 75 years
 PFO seen in persons younger than 50
years.
 In patients with normal sinus rhythm, the
prevalence of
 left atrial thrombus 0.9%
 PFO 25%
Cardioembolic Source
Evaluation for Cardioembolic Source

 A thorough history, physical examination,

ECG, and chest radiography should
provide clues to most major cardiac
sources of embolism
 Transthoracic echocardiography (TTE)
 noninvasive
 better estimate of left ventricular function and
the presence of left ventricular thrombus than
TEE
Evaluation for Cardioembolic Source
 TEE is more sensitive than TTE for
detecting
 aortic atheromatous disease or dissection,
 left atrial thrombus
 PFO

 Most minor sources detected by TEE have

no definitive treatment strategies
Evaluation for Cardioembolic Source

 The yield of echocardiography is higher in

patients
 history or examination findings suggestive of
cardiac disease
 cortical rather than subcortical stroke
 an abnormal ECG
Evaluation for Cardioembolic Source

 Holter monitoring or continuous telemetry

may be useful in patients with
 history of palpitations,
 paroxysmal atrial fibrillation,
 evidence of SEC on TEE, and
 cryptogenic TIA or cerebral infarction in young
people.
Treatment of Cardioembolic Source

 Anticoagulants are superior to aspirin in

primary and secondary prevention of
stroke in patients with atrial fibrillation
 Anticoagulants are preferred over
antiplatelet agents
 patients with prosthetic valves
 left ventricular or atrial thrombus
 Acute MI and left vent. thrombus
 Acute MI in whom LV mural thrombus
is identified by echocardiography
 oral anticoagulation is reasonable (INR of
2.0 to 3.0) for at least 3 months and up to
1 year
 Cardiomyopathy
 In the SAVE study (survival and ventricular
enlargement trial)
 EF of 29% to 35% (mean, 32%) had a stroke
rate of 0.8% per year;
 EF 28% (mean, 23%) was 1.7% per year
 There was an 18% increment in the risk of
stroke for every 5% decline in EF

 Pfeffer MA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular
dysfunction after myocardial infarction: results of the survival and ventricular enlargement
trial: the SAVE Investigators. N Engl J Med. 1992; 327: 669–677
 Cardiomyopathy
 Dilated cardiomyopathy
 either warfarin (INR, 2.0 to 3.0) or
antiplatelet therapy may be considered for
prevention of recurrent events
 PFO/Recommendations

 For patients with an ischemic stroke or

TIA and a PFO, antiplatelet therapy is
reasonable to prevent a recurrent event
 Warfarin is reasonable who have other
indications for oral anticoagulation
such as those with an underlying
hypercoagulable state or evidence of
venous thrombosis
 PFO/Recommendations

 Insufficient data exist to make a

recommendation about PFO closure in
patients with a first stroke and a PFO
 PFO closure may be considered for
patients with recurrent cryptogenic
stroke despite optimal medical therapy
 Which of the following has been shown to
reduce the risk of stroke ( relative to
placebo) in patients with A- Fib.?

 A. Aspirin
 B. Clopidogrel ( Plavix)
 C. ER dipyridamole
 D. IM dipyridamole
 E. Ticlopidine
 Large Vessel Extracranial Source

 15% to 20% of strokes are secondary to

large-vessel disease.
 More than 75% of large-vessel disease is
due to extracranial disease, i.e,
 the extracranial portion of the carotid artery,
the vertebral artery (VA), or the aorta.
 Large Vessel Extracranial Source
 The etiology of extracranial carotid or
vertebral disease
 Atherosclerosis- most common
 dissection
 Takayasu arteritis, giant cell arteritis, and
fibromuscular dysplasia.
 Aortic disease is as a source of cerebral
infarction
 An aortic plaque of 4 mm or greater is an
independent stroke risk.
Evaluation for Large Vessel Extracranial
Source

 Carotid Duplex
 The sensitivity and specificity to detect ICA
stenosis greater than 70% range from 87% to
95% and 86% to 97%, respectively.
Evaluation for Large Vessel Extracranial
Source

 CT- Angiogram
 The sensitivity and specificity of CTA to
determine ICA stenosis greater than 70% are
74% to 100% and 83% to 100%, respectively.
Evaluation for Large Vessel Extracranial
Source

 MRA
 A sensitivity of 83% to 95% and a specificity
of 89% to 94% for detection of extracranial
ICA stenosis greater than 70%
 Evaluation for Large Vessel Extracranial
Source

 MRA, CT angiography (CTA), or

conventional angiography may be superior
 fibromuscular dysplasia
 arteritis
 Dissection
 TEE is superior to MRA of the aortic arch
for detection and quantification of aortic
plaque
Evaluation for Large Vessel Extracranial
Source
 Conventional arteriography is considered the
gold standard
 arteritis
 degree of ICA stenosis
 Dissection
 fibromuscular dysplasia
 limitations of arteriography
 Additional cost
 0.5% to 1% chances of cerebral infarction, TIA, or
hematoma formation during the procedure
 Recommendations

 Cerebral infarction or TIA referable to the

anterior circulation
 If dissection is a concern, MRA or CTA may
be considered first
 If the patient is older than 55 years and has
typical atherosclerotic risk factors, carotid
ultrasonography should be considered first
 Recommendations

 If the patient has symptoms localized to

the posterior circulation
 MRA or CTA of the neck should be

considered
Treatment of Large Vessel Extracranial
Source

 CEA in patients withsymptomatic carotid

stenosis of 70% or greater
 The NASCET results for that group indicate an
11.3% absolute reduction annually in ipsilateral
stroke.
 Number needed to treat (NNT) with CEA to
prevent 1 stroke among that population would
be 9
 Indications for CEA

 Symptomatic 50% or greater carotid stenosis

 aged =<80 years
 if surgical risk for stroke and death is 6% to 7% or
less
 Asymptomatic 60% or greater carotid stenosis
 =<80 years,
 if surgical risk for stroke and death is 3% or less
 less than 50% stenosis or complete occlusion
 no evidence for the benefit of CEA
Treatment of Large Vessel Extracranial
Source
 Alternative to CEA
 Carotid angioplasty and carotid artery stenting
(CAS)
 Standard of care for treatment of carotid
stenosis
 CEA.
 Antiplatelet agents are recommended after
CEA or CAS.
 HMG Co-A reductase inhibitors (statins)
reduce carotid intimal media thickness
 Treatment of Large Vessel Extracranial
Source

 Carotid or Vertebral Dissection

 No randomized clinical trial data address the
issue of whether anticoagulants are better
than antiplatelet agents
 Many clinicians give anticoagulants to
patients with dissection for 3 to 6 months and
then switch to an antiplatelet agent
 Treatment of Large Vessel Extracranial
Source

 Among patients with significant carotid

stenosis, CEA is likely to be most
beneficial in patients whose TIA
characterized by following?
 A. Amaurosis Fugas
 B. Aphasia and facial droop
 C. Ataxic hemiparesis
 D. Pure hemiparesis
 E. pure hemisensory loss
Treatment of Large Vessel Extracranial
Source

 Aortic Atherosclerosis
 the best antithrombotic management is not defined
 Large Vessel Intracranial Source

 5% to 8% of strokes are due to large-vessel

intracranial disease.
 Intracranial disease may be due
 atherosclerosis
 dissection
 vasculitis,
 Moya Moya disease, and
 vasospasm
 Large Vessel Intracranial Source

 Options for evaluation of intracranial

disease includes
 MRA-sensitivity to detect stenosis greater
than 50% is more than 85%
 CTA
 transcranial Doppler ultrasonography
 Conventional arteriography
Treatment of Intracranial Stenosis.

 WARSS trial
 There was no difference in patients
randomized to warfarin (INR, 1.4-2.8) or
aspirin (325 mg/d).
 Another study
 Warfarin was not superior to aspirin in this
prospective study
 Endovascular intervention for intracranial
stenosis is evolving.
 Small Vessel Disease
(Lacunar Stroke)
 Lacunar infarctions
 Up to 20% of all cerebral ischemic events
 Microscopically associated with
microatheroma, lipohyalinosis, and fibrinoid
necrosis
 Increase incidence in patients with
atherosclerotic risk factors, like
hypertension, smoking, and diabetes.
 Lacunar Stroke

 A lacunar infarction is a small subcortical

infarction (less than 1.5 cm) that results
from the occlusion of a penetrating end
artery.

 Lacunes predominate in the basal ganglia,

thalamus, centrum semiovale, brainstem,
and internal capsule.
Lacunar Stroke
 Lacunar Stroke
 In one study, the mechanisms of lacunar stroke
were
 75% small-vessel disease,
 9% atherosclerosis,
 5% cardioembolic,
 9% cryptogenic, and
 2% unusual.

 25% of persons presenting with lacunar stroke

could have other potential mechanisms
warranting alternative treatment.
Gan R, Sacco RL, Kargman DE, Roberts JK, Boden-Albala B, Gu Q. Testing the validity of the lacunar hypothesis: the
Northern Manhattan Stroke Study experience. Neurology. 1997;48:1204-1211.
 Coagulation Disorders

 Coagulation disorders account for 1% to

4.8% of all strokes
 Prevalence increases in patients
 younger than 45 years,
 history of clotting dysfunction, and
 cryptogenic stroke.
Prevalence of Coagulation Abnormalities
in the General Population
 Coagulation Disorders
 Factor V Leiden mutation and prothrombin
20210 mutations may result in cerebral
venous thrombosis
 In all patients, the CBC, aPTT, INR, and
erythrocyte sedimentation rate should be
determined.
 Patients that may require additional testing
 younger than 45 years
 personal or family history of clotting disorders
 venous infarction
Cerebrovascular Risk Factors
 A 69 year old man presented with abrupt onset of
right hemiparesis and expressive aphasia. His past
medical history is remarkable for HTN, DM,
hypercholesterolemia and smoking. His examination
showed BP 180/90. He has mild expressive aphasia,
right facial weakness and 4/5 strength in his right
arm. His symptom improves in next 30 min.
His CT head w/o contrast was negative. Carotid
duplex showed 50% ICA stenosis bilaterally. His EKG
reveals NSR. TEE showed PFO. Which of the
following is most important modifiable risk factor in
this patient for future risk of stroke?
 A. Hypercholesterolemia
 B. DM
 C. HTN
 D. PFO
 E. Smoking
 Acute Ischemic Stroke

 The goal of acute ischemic stroke

treatment is to minimize damage to
the brain by preserving cells and
restoring blood flow.
 Acute Ischemic Stroke

 In humans, normal cerebral blood flow is

approximately 50 to 60 mL/100 g of brain
tissue per minute.

 When flow decreases to less than 10 to 15

mL/100 g per minute, irreversible tissue
damage occurs.
 Ischemic Penumbra/“Potentially
Reversible” Ischemic Tissue
 Irreversible cellular
damage occurs within the
central core.
 Around this core is a
region of decreased flow
in which the threshold for
cell death has not yet
been reached, the so-
called ischemic
penumbra.
 Restoration of blood flow
may preserve the
penumbra, limiting
irreversible damage.
 Ischemic Penumbra

 Cells in the penumbra

can be preserved
either by preventing or
limiting cellular death
or by restoring blood
flow.
 Restoring the blood
flow is the presumed
mechanism of
intravenous
thrombolytic therapy.
Acute Ischemic Stroke-Management

 Patients should be given oxygen therapy

via nasal cannula per Advanced Cardiac
Life Support protocol.

 Unless an allergy exists or patients are

candidates for thrombolytic therapy, all
patients should receive aspirin in the
emergency department.
Acute Ischemic Stroke-Management

 If allergy to aspirin than clopidogrel at a

loading dose of 300 mg by mouth, can be
given

 Patients who have received aspirin in ED,

is not a contraindication to thrombolytic
therapy.
 Initial Evaluation
 Initial evaluation in the ED setting includes blood
glucose level, electrolyte panel including
creatinine level, complete blood cell count,
cardiac biomarker panel and coagulation studies
(PT, PTT, INR)
 Electrocardiography should be performed to rule
out atrial fibrillation or acute myocardial infarction
 Chest radiography should be performed as well
 CT head w/o contrast
 Intravenous Thrombolytic Therapy
for Acute Ischemic Stroke

 In 1995, the results of a clinical trial that

used r-tPA to treat ischemic stroke within 3
hours from symptom onset were
published.
Intravenous Thrombolytic Therapy
for Acute Ischemic Stroke

 The findings showed, at 3 months, there

was an 11% absolute increase in the
number of patients with little or no deficits
among those receiving tPA compared with
those receiving placebo.
Intravenous Thrombolytic Therapy
for Acute Ischemic Stroke

 There was a 6% increase in symptomatic

intracerebral hemorrhage in those
receiving tPA
Intravenous Thrombolytic Therapy
for Acute Ischemic Stroke

 a rigorous protocol must be followed

 Adherence to the 3-hour time limit from

onset of symptoms to treatment is
important because treatment after a
longer time interval has not shown
beneficial effect.
 r-tPA Protocol

 Inclusion Criteria

 Clinical diagnosis of stroke and onset of

symptoms within 3 hour before initiation of
r-tPA.
 Exclusion Criteria

 Historical
 Stroke or head trauma within 3 months
 Any prior history of intracranial
hemorrhage
 Exclusion Criteria

 Clinical
 Rapidly improving stroke symptoms
 Only minor or isolated neurologic signs
 Seizure at onset of stroke
 Symptoms suggestive of SAH, even CT
head is normal
 Exclusion Criteria

 Laboratory
 Platelet count <100,000/mm3
 Blood Glucose < 50 or >400 mg/dl
 INR >1.7 , if on warfarin
 elevated PTT if on heparin
 Exclusion Criteria

 CT head
 Hemorrhage
 Evidence of major early infarct signs,
such as diffuse swelling, hypodensity
and/or effacement of >33% of MCA
territory
 Consent From Patient Or Family

 Patient or family
is aware of risk of
bleeding into the brain is 1 in 16

 Potential benefit: 30% greater chance of

improvement to no or minimal disability

 Patient or family sign consent form

CT Head
 Treatment Guidelines

 Dose
 0.9 mg/kg of body weight (max 90 mg)
 10 % given as a bolus
 Remaining 90% as a constant infusion over 60
min

 All patient should be admitted to ICU

 Posttreartment Guidelines

 Antithrombotic and antiplatelets

agents should not be used for first 24
hours post tPA

 Closely monitor BP for first 24 hour

post tPA
 Blood Pressure Management

 Thrombolytic therapy (first 24 hour)

 MAP <=120 mm Hg
 SBP <= 180 mm Hg

 DBP <= 105 mm Hg

 Blood Pressure Management
 Systolic BP 180-230 or diastolic BP 105-
120 with 2 readings 5 minutes apart
 Give IV Labetalol 10 mg over 1- 2 minutes.
Dose may be repeated or doubled every 10-20
min up to a total of 300
 Esmolol, 500 µg/kg intravenously as a loading
dose over 1 minute, then 50 µg/kg/min and
dosage is titrated to blood pressure
parameters
 Blood Pressure Management

 For BP systolic > 230 or diastolic 121-140

 If no satisfactory response with Labetolol,

start Nitroprusside (0.5-1 mcg/kg/min)
Continue monitoring blood pressure every 15
minutes.
•
Questions?