AOA/OMED 10/1/13
Eric P. Baron, DO
Cleveland Clinic Neurological
Institute
Center for Regional Neurology
 In 2008, fell from 3rd to 4th leading cause of death in the
US after heart disease, cancer, and chronic lower
respiratory diseases
 >795,000 people in US have a stroke each year.
-About 610,000 of these are first or new strokes.
-1 in 4 are recurrent strokes.
 >137,000 deaths each year (1 in every 18 deaths)
http://www.strokeassociation.org/STROKEORG/AboutStroke/Impact-of-Stroke-Strokestatistics_UCM_310728_Article.jsp
 About 40% of stroke deaths occur in males, and
60% in females.
 An American has a stroke every 40 seconds, and
every 4 minutes someone dies of stroke.
 Stroke costs the US >$38.6 billion per year
http://www.strokeassociation.org/STROKEORG/AboutStroke/Impact-of-Stroke-Strokestatistics_UCM_310728_Article.jsp
Ischemic Stroke (87%)
A thrombus or embolus blocks
blood flow to part of the brain.
Hemorrhagic Stroke (13%)
Blood spills out from break
in blood vessel in brain
 Ischemic = 87%
- 45% Atherothrombotic
- 20% Cardioembolic
- 20% Cryptogenic
- 2% Other
 Hemorrhagic = 13%
- 10% Intracerebral hemorrhage
- 3% Subarachnoid hemorrhage
• Each hour:
-120 million neurons, 830 billion synapses, and 714 km (447
miles) of myelinated fibers are lost.
-Compared with normal rate of neuron loss in brain aging, the
ischemic brain ages 3.6 years each hour without treatment.
• Each minute:
-1.9 million neurons, 14 billion synapses, and 12 km (7.5
miles) of myelinated fibers are destroyed.
• Each second:
-30,000 neurons
 Classical definition (1960s): Sudden, neurological deficit,
usually focal, lasting < 24 hours.
NIH Consensus Statement. Stroke 1975;6:564-616.
 Newer definition (2002): Sudden neurological deficit
lasting less than 1 hour and not associated with new
lesion on neuroimaging. (e.g. DWI on MRI)
Albers GW et al. N Eng J Med 2002;347(21):1713-1716.
 New AHA endorsed definition (2009): A transient episode
of neurological dysfunction caused by focal brain, spinal
cord, or retinal ischemia, without acute infarction.
Easton JD et al. Stroke 2009;40:2276-2293.
TRANSIENT ISCHEMIC ATTACK
(TIA)
 Reversible neurologic deficits typically <30 minutes
and usually resolve within 1 hour, although may last
up to 24 hours.
 Often called a “mini-stroke”
 Due to a temporary disruption of the blood supply to
the brain
 WARNING SIGN FOR STROKE
 Risk of stroke after TIA
- 1/3 have continued TIAs
- 1/3 have no further symptoms
- 1/3 stroke within 5 years (usually 1st month)
- 50% have stroke in next 2 days
- 10% have stroke in next 3 months
- 15% have stroke in 1 year
- 25% have stroke in 5 years
http://www.theanswerpage.com/qod.php?specialty_id=4&day=06
/26/2012
TRANSIENT ISCHEMIC ATTACK
(TIA)
 40-60% of TIA pts have evidence of ischemic injury on
DWI (Diffusion Weighted Imaging)
 Factors predicting positive DWI:
• Symptoms lasting > 60 minutes
• Focal weakness
• Speech impairment
Kidwell C et al. Stroke 1999; 6:1174-1180.
Couttts SB et al. Annals of Neurology 2005;57:848-854
Class I Recommendations
• Patients with TIA should preferably undergo
neuroimaging evaluation within 24 hours of symptom
onset. MRI, including DWI, is the preferred brain
diagnostic imaging modality. If MRI is not available, head
CT should be performed (Class I, LOE B).
• Noninvasive imaging of the cervicocephalic vessels
should be performed routinely as part of the evaluation
of patients with suspected TIAs (Class I, LOE A).
© 2009, American Heart Association. All rights reserved.
Easton JD et al. Stroke. 2009;40:2276-2293.
Class II Recommendations
• Initial assessment of the extracranial vasculature may
involve any of the following: carotid ultrasound/TCD,
MRA or CTA, depending on local availability and
expertise, and characteristics of the patient (Class IIa,
Level of Evidence B).
• If only noninvasive testing is performed prior to
endarterectomy, it is reasonable to pursue two
concordant noninvasive findings; otherwise catheter
angiography should be considered (Class IIa, Level of
Evidence B).
© 2009, American Heart Association. All rights reserved.
Easton JD et al. Stroke. 2009;40:2276-2293.
Class II Recommendations
• Electrocardiography should occur as soon as possible after TIA
(Class I, Level of Evidence B). Prolonged cardiac monitoring
(inpatient telemetry or Holter monitor) is useful in patients with
an unclear etiology after initial brain imaging and
electrocardiography (Class IIa,
LOE B).
• Echocardiography (at least TTE) is reasonable in the
evaluation of patients with suspected TIAs, especially when the
patient has no cause is identified by other elements of the
work-up (Class IIa, Level of Evidence B). TEE is useful in
identifying patent foramen ovale, aortic arch atherosclerosis,
and valvular disease and is reasonable when identification of
these conditions will alter management (Class IIa, LOE B).
© 2009, American Heart Association. All rights reserved.
Easton JD et al. Stroke. 2009;40:2276-2293.
Class II Recommendations
•
It is reasonable to hospitalize patients with TIA if they
present within 72 hours of the event and any of the
following criteria are present:
– ABCD2 score of ≥3, (Class IIa, LOE C).
– ABCD2 score of 0-2 and uncertainty that diagnostic
work-up can be completed within 2 days as an
outpatient (Class IIa, LOE C).
– ABCD2 score of 0-2 and there is other evidence that
indicates the patient’s event was caused by focal
ischemia (Class IIa, LOE C).
© 2009, American Heart Association. All rights reserved.
Easton JD et al. Stroke. 2009;40:2276-2293.
CCHS ENTERPRISE TIA MANAGEMENT PROCESS
(DRAFT)
Patient presents to ED with a transient
epsiode of neurological dysfunction
suspicous for focal brain, spinal cord, or
retinal ischemia
Non-contrast
Head CT shows
acute brain
infarction
Evaluation
Bloodwork:
CBC, CMP, PTT, INR, Fasting Lipids,
HGBA1C, CK, Troponin
Hypercoag panel (cryptogenic embolism)
Tissue Imaging: MRI (preferred)
CT
Vascular Imaging: MRA (preferred)
Carotid Duplex/TCD
CTA
Cardiac:
12-Lead EKG
Telemetry
TTE
TEE
Yes
Admit to Hospital
Dx: Acute Ischemic Stroke
(434.91)
No
No
Patient &
Clinician report
symptoms
resolved
Management
Risk Factor Modification
Hypertension (JNC 8 Targets)
Diabetes Mellitus (HGBA1C less than 7.0)
Dyslipidemia (ATP4 Targets)
Tobacco Use (Smoking Cessation)
Obesity (Healthy Diet)
Exercise (30 minutes of walking most days)
Antithrombotic Therapy
Antiplatelet
Aspirin
Clopidogrel
Aggrenox
Anticoagulation Warfarin
Apixaban
Dabigatran
Rivaroxaban
Yes
ABCD2 Score
Age≥60
BP≥140/90mm Hg
Clinical Symptoms
Focal weakness or
Speech impaired
Duration
>60 minutes or
10-59 minutes
Diabetes
Total
Version 1/14/13
1
1
<3
Observation Status
Dx: Acute Transient
Cerebral Ischemia (435.9)
2
1
2
1
1
(0-7)
≥3
Admit to Hospital
Dx: Acute Transient
Cerebral Ischemia (435.9)
 Hypertension (high blood pressure)
 Exposure to cigarette smoking (active or passive)
 Diabetes
 Atrial fibrillation and other cardiac conditions
 Hyperlipidemia (high cholesterol)
 Carotid artery stenosis
 Sickle cell disease
 Postmenopausal hormone therapy
 Poor Diet
 Physical Inactivity
 Obesity and body fat distribution
HYPERTENSION
 Most important risk factor for stroke.
 Causes a 2-4 fold increase in the risk of
stroke before age 80.
 Prior Stroke or TIA:
- LDL < 100
 Known coronary heart disease or coronary heart
disease risk equivalents (diabetes, peripheral arterial
disease, abdominal aortic aneurysm, or carotid
artery disease):
- LDL < 70
(ATP III Guidelines)
 Causes a 2-fold increase in risk of ischemic stroke and up to a 4-fold
increase in risk of hemorrhagic stroke.
 Linked to the buildup of atherosclerosis.
 Nicotine raises BP; CO from smoking reduces the amount of oxygen
blood can carry to the brain; and cigarette smoke makes blood thicker
and more likely to clot.
 Promotes aneurysm formation.
 Stopping smoking causes a 50% risk reduction for stroke within 1 year.
 Stopping smoking causes stroke risk to approach that of nonsmokers
after 5 years.
DIABETES
 Having diabetes is the equivalent of aging 15 years.
 Causes destructive changes in the blood vessels
throughout the body, including the brain.
 If blood glucose levels are high at the time of a
stroke, then brain damage is usually more severe
and extensive than when blood glucose is wellcontrolled.
 HTN is common among diabetics and accounts for
much of the increased stroke risk.
 In general, increases stroke risk by 5-fold.
 Responsible for 1 in 4 strokes after age 80, and is
associated with higher mortality and disability.
 CHADS2 Score is helpful in deciding on
anticoagulation:
-Low risk (0): Aspirin 100-300 mg daily
-Moderate risk (1): Warfarin or Aspirin
-High risk (2-6): Warfarin (INR 2-3)
 Warfarin (Class I; Level of Evidence A)
 Dabigatran 150 mg bid (Class I; Level of Evidence B)
-CrCl >30 mL/min
 Apixaban 5 mg bid (Class I; Level of Evidence B)
-No more than 1 of the following characteristics: Age >80
years, weight <60 kg, creatinine >1.5 mg/dL
 Rivaroxaban 20 mg/d (Class IIa; Level of Evidence B)
-CrCl >50
 Recent TIA or ischemic stroke w/in 6 months and
ipsilateral severe (70%-99%) carotid stenosis:
-CEA recommended if perioperative morbidity and mortality
risk estimated at <6% (Class I; Level of Evidence A).
 Recent TIA or ischemic stroke and ipsilateral moderate
(50%-69%) carotid stenosis:
-CEA recommended depending on patient-specific factors
such as age, sex, and comorbidities if perioperative
morbidity and mortality risk estimated at <6% (Class I;
Level of Evidence B).
 Stenosis <50%:
-No indication for carotid revascularization by either
CEA or CAS (Class III; Level of Evidence A).
 When CEA is indicated for patients with TIA or
stroke, surgery w/in 2 weeks is reasonable rather
than delaying surgery if no contraindications to early
revascularization (Class IIa; Level of Evidence B).
 CAS indicated as alternative to CEA for symptomatic
patients at average to low risk of complications
associated with endovascular intervention when ICA
stenosis >70% by noninvasive imaging or >50% by
catheter angiography (Class I; Level of Evidence B).
 Among patients with symptomatic severe stenosis
(>70%) in whom the stenosis is difficult to access
surgically, medical conditions are present that greatly
increase the risk for surgery, or when other specific
circumstances exist, such as radiation-induced stenosis
or restenosis after CEA, CAS may be considered (Class
IIb; Level of Evidence B).
 CAS in the above setting is reasonable when performed
by operators with established periprocedural morbidity
and mortality rates of 4-6%, similar to those observed in
trials of CEA and CAS (Class IIa; Level of Evidence B).
 For patients with symptomatic extracranial carotid
occlusion, EC/IC bypass surgery is not routinely
recommended (Class III; Level of Evidence A).
 Optimal medical therapy, which should include
antiplatelet therapy, statin therapy, and risk
factor modification, is recommended for all patients
with carotid artery stenosis and a TIA or stroke as
outlined elsewhere in this guideline (Class I; Level of
Evidence B).
 Optimal medical therapy, which should include
antiplatelet therapy, statin therapy, and risk
factor modification, is recommended for all patients
with vertebral artery stenosis and a TIA or stroke as
outlined elsewhere in this guideline (Class I; Level of
Evidence B).
 Endovascular and surgical treatment of patients with
extracranial vertebral stenosis may be considered
when patients are having symptoms despite optimal
medical treatment (including antithrombotics, statins,
and relevant risk factor control) (Class IIb; Level of
Evidence C)
 For patients with a stroke or TIA due to 50%-99%
stenosis of a major intracranial artery, aspirin is
recommended in preference to warfarin (Class I;
Level of Evidence B).
- Patients in the WASID trial were treated with aspirin
1300 mg/d, but the optimal dose of aspirin in this
population has not been determined.
- On the basis of data on general safety and efficacy,
aspirin doses of 50 mg/d to 325 mg/d are
recommended (Class I; Level of Evidence B).
 For patients with stroke or TIA due to 50% to 99%
stenosis of a major intracranial artery, long-term
maintenance of BP <140/90 mm Hg and total
cholesterol level <200 mg/dL may be reasonable
(Class IIb; Level of Evidence B).
 For patients with stroke or TIA due to 50%-99%
stenosis of a major intracranial artery, the usefulness
of angioplasty and/or stent placement is unknown
and is considered investigational (Class IIb; Level of
Evidence C).
 For patients with stroke or TIA due to 50%-99%
stenosis of a major intracranial artery, EC/IC bypass
surgery is not recommended (Class III; Level of
Evidence B).
 Age
 Sex
 Low birth weight
 Race/ethnicity
 Genetic predisposition
 Stroke occurs in all age groups, including childhood
or adolescence.
 Studies show the risk of stroke doubles for each
decade between the ages of 55 and 85.
 Men have a higher risk for stroke, but more women
die from stroke.
 Men generally do not live as long as women, so men
are usually younger when they have their strokes
and therefore have a higher rate of survival.
 In African Americans stroke is more common and
more deadly across all age groups.
 Studies show that the age-adjusted incidence of
stroke is about twice as high in African Americans
and Hispanic Americans as in Caucasians.
 An important risk factor for African-Americans is
sickle cell disease, which can cause a narrowing of
arteries and disrupt blood flow.
 Members of a family might have a genetic tendency
for stroke risk factors, such as an inherited
predisposition for HTN, HLP, DM, etc.
 The influence of a common lifestyle among family
members also could contribute to familial stroke.
 Stroke risk factor modifications (including antiplatelet
therapy (or anticoagulation if indicated), HLP, HTN,
DM, Smoking, etc.):
-Primary (prior to an event)
-Secondary (following an event)
 Improving patient education for rapid symptom
evaluation due to short intervention treatment
windows (tPA)
Severe headache with no known cause
Trouble seeing in one or both eyes
Confusion, trouble speaking or understanding
Numbness or weakness of face, arm or leg,
especially on one side
Trouble walking, dizziness, loss of balance
or coordination
 Cardiac monitoring
 BP
- <180/105 following tPA and lower BP by 15% per day
- <220/120 if no tPA and lower BP by 15% per day
 Airway support as needed and O2 sats >94%
 Temp < 38°C (100.4°F)
 Treat hypoglycemia (<60 mg/dL) and hyperglycemia
(optimal range 140-180 mg/dL)
 Treat hypovolemia with IV NS
 Head of bed 15-30°
 Catalyzes the conversion of plasminogen to plasmin,
the major enzyme responsible for clot breakdown.
 0.9 mg/kg IV (max dose 90 mg)
-10% given as a bolus over 1 minute
-Remaining 90% continuous infusion over 60 minutes
 No antiplatelet/anticoagulants x 24 hours post-tPA
 NINDS trial in 1995 (National Institute of
Neurological Disorders and Stroke) rtPA
Stroke Study Group:
-In 1996 US FDA approved IV tPA for acute
ischemic stroke within 3 hrs of symptom
onset (Class I; Level of Evidence A)
 ECASS-3 trial in 2008 (European Cooperative
Acute Stroke Study) showed an extended
window from 3-4.5 hours of symptom onset.
-European Medicines Agency expanded
approval of IV tPA to the 3-4.5 hour window.
-US FDA has not officially approved this.
-However, AHA/ASA has labeled this Class I;
Level of Evidence B in revised stroke
guidelines published 1/31/13, and is considered
standard of care.
 Modified Rankin Scale of 0-1 at 3 months:
NINDS:
 39% (rtPA) vs. 26% (control)
 OR 1.7 (1.1-2.6) P = 0.019
ECASS-3:
 52% (rtPA) vs. 45% (control)
 OR 1.34 (1.02-1.74) P = 0.04
 Symptomatic ICH (NINDS definition):
NINDS:
 6.4% vs. 0.6% (placebo) P < 0.001
ECASS-3:
 7.9% vs. 3.5% (placebo) P = 0.006
 Death at 3 months:
NINDS:
 17% vs. 24% (placebo) P = 0.3
ECASS-3:
 32% vs. 34% (placebo) P = 0.68
 30% greater chance of good neurologic outcome at 3
months with IV tPA compared to without
 NNT to obtain significant benefit in 1 patient within 3 hour
window: 8
 NNT to obtain significant benefit in 1 patient within 3-4.5
hour window: 23
 40% get better with tPA, 28% get better without tPA,
(12% absolute benefit)
 Significant increase in risk of ICH: 6.4% (<3 hours) vs.
7.9% (3-4.5 hours)
 Diagnosis of ischemic stroke causing measurable
neurological deficit.
 Onset of symptoms <3 hours before beginning
treatment (see below for 3-4.5 hours after onset).
 Age ≥ 18 years old
 Significant head trauma or stroke in previous 3
mths.
 Intracranial neoplasm, aneurysm, or AVM.
 Symptoms of stroke should not be suggestive of
subarachnoid hemorrhage.
 Arterial puncture at a noncompressible site in
previous 7 days.
 History of previous intracranial hemorrhage.
 Recent intracranial or intraspinal surgery.
 BP elevated (>185/110 mm Hg).
 Evidence of active internal bleeding or acute
trauma (fracture) on exam.
 Anticoagulant use with INR >1.7 or PT >15.
 Taking a direct thrombin inhibitor or factor Xa
within 48 hours or with elevated aPTT, INR,
ECT (ecarin clotting time), TT (thrombin time),
or appropriate factor Xa assay.
 If received heparin in previous 48 hours, aPTT
must be in normal range.
 Platelet count <100,000 mm3.
 Blood glucose concentration <50 mg/dL (2.7
mmol/L) (serum glucose is only lab test that
MUST be obtained before starting tPA).
 CT shows multilobar infarction (hypodensity >1/3
cerebral hemisphere). tPA may be given if other
early ischemic changes are seen on CT.
 GI or GU hemorrhage in previous 21 days.
 Major surgery or major trauma in previous 14
days.
 Seizure at onset with postictal residual
neurological impairments.
 Myocardial infarction in the previous 3 months.
 Pregnancy.
 Minor or rapidly improving neurological
symptoms.
 Same as those for earlier time periods, with any 1 of
the following 4 additional exclusion criteria:
1. Age > 80 years old.
2. Any oral anticoagulant use, regardless of INR.
3. Severe stroke (NIHSS score >25).
4. Those with both history of stroke and diabetes.
ACUTE STROKE TREATMENT:
> 4.5 HOURS OR IV TPA CONTRAINDICATED
 Intraarterial (IA) tPA within 6 hours (Class I;
Level of Evidence B)
- tPA does not have FDA approval for IA use
 Mechanical Thrombectomy:
- Within 8 hours in anterior circulation
- Less defined in posterior circulation, possibly
up to 24-36 hours in some cases
- Stent retrievers generally preferred to coil
retrievers (Class I; Level of Evidence A)
http://www.karger.com/Article/Fulltext/338903
 TIA should be treated as impending stroke
 The period of greatest risk for stroke is within 48




hours of a TIA
Simple clinical features can predict those patients
with TIA at greatest stroke risk
IV tPA is indicated for acute ischemic stroke within 3
hours, and now up to 4.5 hours in select patients.
IA tPA is indicated for acute ischemic stroke within 6
hours.
Mechanical thrombectomy is indicated for acute
ischemic stroke within 8 hours.
THANK YOU