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© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
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© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
in the clinic
Transient
Ischemic Attack
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What is a transient ischemic attack?
 Classical definition: Episode of focal cerebral, retinal, or
spinal cord ischemia causing transient neurologic
dysfunction lasting <24 h (most TIAs resolve in <1 h)
But : despite complete symptom resolution… 20%-50%
w/TIA have evidence of acute tissue infarction on MRI
 AHA revised definition: TIA should only refer to transient
episode of neurologic dysfunction due to ischemia w/o
evidence acute infarction, regardless symptom duration
 Intent:
 Better align terminology w/actual disease process
 Encourage neurodiagnostic testing to ID brain injury
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What is a transient ischemic attack?
 TIA and ischemic stroke fundamentally identical disease
processes
 Differ in:
 Duration & degree of cerebral ischemia
 Whether permanent detectable brain injury
ensues (radiographic/clinical)
 Shared pathophysiology supports data extrapolation
from selected clinical trials of stroke Rxs to pts w/TIA
 Most TIA studies to date use “classical definition”
 this review uses “classical definition”
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What causes TIA and what are the risk
factors?
 Mechanism of TIA is…
 Large artery atherosclerosis (~20%-25%)
 Cardioembolism (10%-15%)
 Small vessel disease (10%-15%)
 Unusual diverse rare causes (~5%)
 Undetermined cause (~50%)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
 Common Risk Factors for TIA and Stroke
 Age >50 y
 Hypertension
 Diabetes mellitus
 Elevated cholesterol levels
 Smoking
 Carotid stenosis
 Hx TIA or stroke
 Hx paroxysmal or persistent AF
 Hx CAD or PAD
 Family Hx CAD, CVD, or PAD before age 60 y
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What is the spectrum of presentations
for patients with TIA?
 Symptoms of TIA
 Impaired speech and/or language
 Visual loss in one or both eyes
 Double vision
 Facial drooping
 Swallowing dysfunction
 Unilateral weakness
 Unilateral sensory loss
 Impaired limb coordination
 Vertigo
 Gait dysfunction
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What is the spectrum of presentations
for patients with TIA?
 Sxs depend on area of ischemia (brain, retina, or spinal cord)
 Lethargy or loss of consciousness atypical  ? alternative Dx
 Vertigo possible, particularly w/other typical symptoms
isolated vertigo only very rarely due to TIA
 Most TIAs quite brief:
60% <1 h, 71% <2 h
Only 14% >6 h
Deficits often resolved by time of medical attention
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
How should clinicians use history
and physical examination to evaluate
patients with suspected TIA?
 Neurologic exam
 May be normal (most resolve by time seen); if persistent
deficits at evaluation  more likely stroke
 “Localize the lesion”  often challenging (patient recall &
description of symptoms may not reliably reflect deficit)
 Unilateral weakness often perceived as heaviness; unilateral
sensory loss often perceived as tingling, pain
 Nonspecific gait dysfunction  common; lateropulsion
suggests focal deficit
 Abnormal speech common  challenge to differentiate if
aphasia or dysarthria
 Blurred vision  may be cortical visual field deficit,
monocular visual loss, or diplopia
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
How should clinicians use history
and physical examination to evaluate
patients with suspected TIA?
 Check for any of the following:
 Carotid artery bruit
 Cardiac arrhythmia or murmur
 Impaired distal pulses
 Fundi: chronic hypertensive vascular changes
 May aid assessment of vascular risk factors
 Identify cause of current event
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What other disorders should clinicians
consider in patients with suspected TIA?
TIA/stroke
 Abrupt onset; fixed focal findings refer to arterial distribution
 DW-MRI abnormal in 20%-50% w/transient symptoms
Seizure
 Abrupt onset and termination; often includes  responsiveness,
involuntary movements, and/or incontinence during; usually lethargy
or confusion after
 Focal findings occur + resolve over hrs to days
 May accompany stroke (~2%-3%)
Hypo-/hyperglycemia
 Usually occurs in pts w/diabetes (diagnose by measuring blood
glucose); may be accompanied by seizure
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
Complicated migraine
 Severe headache usually precedes/follows; sensory & visual
disturbances often prominent; sensory symptoms spread over
affected area slowly
 Younger pts, those w/history severe headache; MRI usually normal;
stroke may accompany
Mass lesion
 e.g., tumor, abscess, herpes encephalitis, subdural hematoma,
demyelination
 Focal symptoms over h to d; may not follow cerebrovascular
territory; 1° cancer, fever, trauma, or immunosuppr’n often present
 Brain imaging distinguishes from stroke
Cervical or lumbar spine disease
 Focal symptoms isolated to peripheral nerve root distribution in
single limb, associated w/depressed reflexes in that region
 Symptom recurrence may be demonstrated w/maneuvers (e.g.,
cervical stretch test)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
Benign paroxysmal positional vertigo
 Very brief (seconds) spells of vertigo precipitated by head
movement
 Reproducible w/Dix-Hallpike maneuver
 Associated w/specific characteristics (torsional nystagmus
w/latency, fatigability)
Psychogenic (functional)
 May look like stroke
 Often not in vascular territory; findings often nonanatomical/
inconsistent
 MRI usually normal
 More likely conversion disorder than malingering
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What diagnostic tests are helpful in diagnosis?
 Brain CT: To exclude brain hemorrhage, large mass lesions, and
identify old areas of infarction
 Brain MRI: Evidence acute infarction in 20%-50% with TIA
 Carotid US: Sensitivity & specificity 80%-90% for carotid bifurcation
stenosis >70%; not helpful for TIA in vertebrobasilar system
 Transcranial doppler US: Sensitivity ~70%; specificity 30%-50% for
intracranial stenosis >50%
 MRA, CTA: Sensitivity & specificity 80%-90% for stenosis >50%;
Gd-enhanced cervical MRA ups accuracy; CTA requires IV contrast
 Catheter angiography: Reference standard; invasive procedure; use
when revascularization considered; requires contrast
 ECHO: To detect intracardiac thrombus, tumors, valve disorders
 EKG: To identify AF
 Serum glucose & hemoglobin A1C: To detect latent diabetes mellitus
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
 Serum lipids: To detect hyperlipidemia
 Clotting studies: Obtain baseline prothrombin/partial thromboplastin
time to prep for possible anticoagulation
 Toxicology screen: To detect sympathomimetic drug use
 Blood cultures: If patient febrile, especially if endocarditis, embolic
stroke, or TIA suspected
 ESR: Patient >50 y: unexplained TIA or headache + possible giant
cell arteritis
 Rheumatologic serologies: If systemic vasculitis or autoimmunemediated hypercoagulable state or valvular disease suspected
 VDRL/RPR testing: Unexplained TIA + possible meningovascular
syphilis
 Hb electrophoresis: For anemia and atypical cerebral vasculopathy
 Genetic testing: For rare inherited diseases associated with stroke
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
When should clinicians consult a
neurologist for the diagnosis of TIA?
 When patient has suspected TIA
 Patients evaluated urgently by stroke specialists
have lower rates of subsequent stroke
 Compared with patients in nonspecialty settings
Early evaluation & therapy associated w/80%
reduction in risk early recurrent stroke
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
CLINICAL BOTTOM LINE: Diagnosis…
 Transient neurologic symptoms characterize TIA
 Evaluate: Are the symptoms due to cerebral ischemia?
 If so, what is the mechanism by which it occurred?
 Perform tests to identify and treat the causes of TIA
 Vascular imaging, electrocardiography, echocardiography
 Lab testing, basic blood work
 Brain MRI-DWI: Sensitive to acute infarction (seen in ~33% of
TIA patients despite symptom resolution)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What is the role of risk assessment in
the acute care of patients with TIA?
 Essential component of management
 Overall: 5.2% stroke risk w/in 7 days  most w/in first 48 h
 Up to 20% stroke risk w/in 90 days in patients with highrisk features of TIA
 Risk of early stroke varies by health care setting:
 Lowest risk in patients receiving emergency Rx from
specialist stroke services (0.9% at 7 days)
 Highest risk in general population-based studies w/o
urgent Rx (11.0% at day 7)
 Observed risk also depends on study methodology 
higher risks in studies w/active outcome ascertainment
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
How should clinicians assess the risk for
subsequent stroke in patients after TIA?
 Clinical risk scores: ABCD2 Score
 Age: ≥60 y = 1 point
 Systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg = 1
point
 Unilateral weakness = 2 points
 Diabetes: yes = 1 point
 Symptom duration: ≥60 min = 2 points; 10-59 min = 1 point
Score
Risk
Stroke Risk
2 Days
7 Days
90 Days
0-3
Low
1.0
1.2
3.1
4-5
Moderate
4.1
5.9
9.8
6-7
High
8.1
11.7
17.8
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
 Brain imaging studies: CT or MRI
 Cerebral infarction = significantly increased shortterm stroke risk
 On CT: indicates background presence of CVD
 On MRI-DWI: provides information about acute clinical
event
 Vascular imaging studies
 Estimate risk
 Identifies candidates for revascularization
 If large-vessel stenosis causes TIA: high short-term
stroke risk
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
Are there any patients with suspected
TIA that are at very low risk for stroke?
 Isolated sensory symptoms lasting <10 min
 Isolated visual symptoms lasting <30 min
 Transient isolated vertigo
 Symptoms may be due to nonvascular process
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
CLINICAL BOTTOM LINE: Risk
stratification…
 Tools help predict who is at highest risk for stroke after TIA

~5%-10% of patients will have a stroke within 1 week
 Clinical risk scores

ABCD2 score: incorporates age, blood pressure, weakness
or speech impairment, duration of event, and Hx of diabetes:
Low score = low short-term risk (~1% at 7 days)
 Brain imaging with CT or MRI-DWI and vascular imaging

Acute infarction on MRI-DWI, old or new infarction on CT, or
large-vessel stenosis on vascular imaging = higher risk in
short-term

Normal MRI-DWI = low risk
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
When should clinicians hospitalize
patients with suspected TIA?
 All patients w/acute TIA
 Observe for 24 hours while determining mechanism
of TIA and treatment strategy
 Patients at high risk for subsequent TIA or stroke
 For intensive treatment and close monitoring
AHA 2009 guidelines: Hospitalize patients with TIA
who present ≤72 hours of symptom onset if:

ABCD2 score ≥3 or

ABCD2 score 0-2 in either: the setting of inability to
complete diagnostic evaluation within 48 h or
evidence of focal ischemia
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What drug therapy should clinicians
consider for patients having acute TIA?
Aspirin
 Antiplatelet: for acute TIA; to prevent stroke
Combined aspirin + dipyridamole
 Antiplatelet: benefit over aspirin alone; similar to clopidogrel
Clopidogrel
 Antiplatelet: for acute TIA in patients with aspirin allergy
Heparin
 Anticoagulant: consider if documented cardioembolic
source, severe large vessel stenosis, history of multiple TIAs
Warfarin
 Anticoagulant: for TIA due to AF; reduces stroke, recurrent TIA
Dabigatran
 Anticoagulant: for TIA due to AF; direct thrombin inhibitor;
more effective than antiplatelet Rx in this setting
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
How should clinicians manage
antihypertensive medications in the
setting of acute TIA?
 In the first 24 h, optimize cerebral blood flow
 Avoid BP-lowering agents (i.e., permissive HTN)
 Use IV normal saline to ensure euvolemia
 Position patient with head of bed flat
 If patient stable for 24 h
 Restart antihypertensive medications
 Do so more cautiously in patients with TIA due to
severe large-vessel stenosis
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
When should clinicians use anticoagulant
and antiplatelet therapy to prevent
recurrent TIA or stroke?
 Warfarin anticoagulation
 If TIA or stroke due to AF: Reduces risk of future stroke
 Oral anticoagulation
 If TIA due to other high-risk cardioembolic sources
 Aspirin + clopidogrel combination
 For patients unable to take warfarin for reasons other than
bleeding risk
 Antiplatelet therapy
 If no cardioembolic TIA source; clopidogrel or ASA-ER DP better
than aspirin to prevent recurrent vascular events after stroke
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What other drug therapy has a role in
preventing recurrent TIA or stroke?
Statins
 Reduce risk for recurrent vascular events after stroke or TIA
 Recommended target LDL <70 mg/dL with atherosclerotic
stroke or TIA
 Multiple mechanisms ameliorate stroke risk
Antihypertensive Agents
 Use outside acute period
 Long-term aggressive BP lowering significantly reduces future
vascular event risk
 Beneficial even in normotensive pts w/stroke or TIA
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
What surgical or other nondrug
therapies can be used to prevent
recurrent TIA or stroke?
 CEA
 If carotid stenosis ≥50%: reduces future stroke risk
(especially when stenosis >70%)
 Best if performed within 2 weeks of TIA, especially when
carotid stenosis 50%-69%
 Carotid angioplasty and stenting
 Alternative to CEA
 Use if surgery contraindicated (high carotid bifurcation,
previous neck radiation, extremely high cardiac risk)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
How should clinicians follow patients
with TIA?
 Focus on controlling vascular risk factors
 Emphasize
 Healthy diet and regular exercise
 Medication compliance
 Smoking cessation
 Pay close attention to new neurologic symptoms that
suggest recurrent TIA or stroke
 In absence of new symptoms, no routine follow-up
studies needed
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.
CLINICAL BOTTOM LINE: Treatment…
 Immediate evaluation important to determine cause of TIA and
strategies to reduce the risk for recurrent TIA or stroke
 Hospitalization appropriate for most patients with acute TIA
 Administer antiplatelet therapy promptly
 Administer long-term anticoagulation to patients with a
cardioembolic source, such as AF
 Consider carotid revascularization for patients with carotid
stenosis >50%, preferably by CEA and within 2 weeks of TIA
 Provide long-term antithrombotic therapy and control of
vascular risk factors to all patients
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (1): ITC1-1.