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The Management of ED TIA Patients:
Michael A. Ross MD FACEP
Associate Professor Emergency Medicine
Department of Emergency Medicine
William Beaumont Hospital
Wayne State University School of Medicine
Michael Ross, MD, FACEP
Case presentation
• A 58 year old female presents to the emergency
department after developing dysarthria, diploplia,
numbness, and pronounced weakness of the right
face and hand that lasted roughly 12 minutes. The
patient feels completely normal and only came in
at her families insistence.
– Review of systems - mild headache with event.
No palpitations, chest pain, or SOB.
– Past medical history - Positive for hypertension
and hyperlipidemia. No prior stroke or TIA.
– Family history positive for premature coronary
disease.
– Meds - Beta-blocker for HTN. Not on aspirin.
– Social - She does not smoke.
Michael Ross, MD, FACEP
Case presentation
• Phyisical Exam:
On examination the patient was normotensive, and
comfortable.
• HEENT exam showed no facial or oral asymmetry or
numbness. No scalp tenderness.
• CHEST exam showed no murmurs and a regular rhythm,
• ABDOMINAL and EXTREMITY exam was normal,
• NEUROLOGICAL exam showed normal mentation, CN IIXII normal as tested, motor / sensory exam normal,
symmetrical normal reflexes, and normal cerebellar exam.
Michael Ross, MD, FACEP
Case presentation
• ED course:
– ECG showed a normal sinus rhythm with mild LVH.
– Non-contrast head CT scan was normal.
– Blood-work (CBC with differential, electrolytes,
BUN/Cr, and glucose) was normal. ESR was normal.
– Monitor showed no dysrhythmias
– Normal subsequent neurological symptoms.
– The patient feels fine and is wondering if she can go
home.
What do you think?
Michael Ross, MD, FACEP
Background
•
300,000 TIAs occur annually - Johnstons’ data
•
Within 90 days:
• 10.5% will suffer a stroke
_
21% will be fatal
_
64% will be disabling
_
Half of these will occur within 1 - 2 days of ED visit
• 2.6% will die
• 2.6% will suffer adverse cardiovascular events
• 12.7% will have additional TIAs
Michael Ross, MD, FACEP
Stroke Risk After TIA
Year
Johnston, et al (Kaiser ED)2000
Eliasew, et al (NASCET) 2004
Lovett, et al (Oxfordshire) 2004
Gladstone, et al (Toronto) 2004
Daffertshofer, et al (Grmy) 2004
Hill, et al (Alberta)
2004
Lisabeth, et al (Texas)
2004
Kleindorfer, et al (Cinc)
2005
Whitehead, et al (Scotland)2005
Correia, et al (Portugal)
2006
Tsivgoulis, et al (Greece) 2006
AVERAGE
N
1707
603
209
371
1150
2285
612
927
205
141
226
Stroke Risk
10.5% /90d
20.1% /90d
12% /30d
5%
/30d
13% /180d
9.5% /90d
4.0% /90d
14.6% /90d
7%
/30d
13% /7d
9.7% /30d
~12% stroke risk in 90 days after TIA
5% in first 2 days
Michael Ross, MD, FACEP
Stroke Risk After Stroke
IST
CAST
TOAST
NASCET
3.3 %/ 3m
1.6%/ 3m
5.7%/ 3m
2.3%/3m
AVERAGE ~4% stroke risk in 90 days after stroke
Michael Ross, MD, FACEP
Pathophysiology
• Short-term risk of stroke:
– After TIA (11%) > after stroke (4%)
• Possible explanation
– Tissue still at risk: unstable situation
• More thrombo-embolic events
Johnston, NEJM 2002; 347:1687
Michael Ross, MD, FACEP
Possible Explanation: Instability
Michael Ross, MD, FACEP
Possible Explanation: Instability
Michael Ross, MD, FACEP
Outside the “head”:
Cardio-embolic
sources
Michael Ross, MD, FACEP
Background
•
Stroke is preceded by TIA in 15% of pts
•
Stroke is the THIRD leading cause of death
–
National cost of stroke = $51 billion annually!
–
Many consider stroke to be worse than death.
Michael Ross, MD, FACEP
TIA
STROKE
Michael Ross, MD, FACEP
Topics to be covered
1. Appropriate history, physical, and labs
2. ECG, monitor, HCT
3. Carotid dopplers - why, when, how?
4. Further clinical testing
5. Therapy – starting with aspirin
Michael Ross, MD, FACEP
TIA Definition
• Traditional
– Neurological deficit lasting less than 24 hours
due to focal ischemia in the brain or retina.
• Newly Proposed
–
–
–
–
A brief episode of neurologic dysfunction
caused by focal brain or retinal ischemia,
with clinical symptoms typically lasting less than 1hr,
and without evidence of acute infarction”.
• If TIA symptoms last >1hr, then >85% have a stroke
– NINDs tPA study data - Albers et al.
Michael Ross, MD, FACEP
1. History and physical:
The History
• Duration - <10min, 10-60min, >60 min
• Evidence to suggest non-vascular cause?
– Focal vs. non-focal symptoms
– Abrupt vs. gradual symptom onset
• Vascular risk factors?
– DM, prior “CVA-TIA-MI-PVD”
• Symptoms to suggest potential causes?
– Neck pain - dissection
– Palpitations - atrial fibrillation
Michael Ross, MD, FACEP
Evaluation:
Physical examination
• Neurologic deficits?
• Carotid bruits (note limitations)?
• Cardiac abnormalities?
– Arrhythmia
– Murmur
– Signs of heart failure
• Symptoms reproducible with provocative
maneuvers?
– Cervical stretch test
– Carpal tunnel positioning tests
Michael Ross, MD, FACEP
Neurological Exam
• Six major areas
– MS, CN II-IX, Motor, Sensory, Reflex, Coordination
• NIH stroke score
– Structured neurological exam
– Validated tool for detection of significant deficits
– Value as an educational tool
– Thrombolytic screening tool
– Google - “NIHSS training”:
http://asa.trainingcampus.net/uas/modules/trees/windex.aspx
– Google - “FERNE” website:
http://www.ferne.org/
Michael Ross, MD, FACEP
Evaluation:
Laboratory testing
• Complete blood count
– anemia, polycythemia,
thrombocytosis/thrombocytopenia
• Chemistry panel
– hypoglycemia, diabetes, renal failure
• Sedimentation rate
– temporal arteritis, endocarditis
• EKG
– prior MI, atrial fibrillation
Michael Ross, MD, FACEP
Unstable plaque with
intense staining for PAPP-A
within spindle shaped
smooth muscle cells and in
extracellular matrix of eroded
plaque
Stable plaque
with absence of
PAPP-A staining
Unstable plaque ; Lp-PLA2
Candidate Blood
Markers???
Unstable Plaque:
Lp-PLA2, PAPP-A, MMP-9,
CRP, S-TF
Coagulation Activation:
D-dimer, F 1.2, TAT
Cardioembolism:
BNP (CHF), D-dimer
Michael Ross, MD, FACEP
TIA: Differential Diagnosis
“Mimics”
•
•
•
•
•
Epilepsy
Complicated migraine
Subdural hematoma
Mass lesions, AVMs
Arterial dissection
• Cervical disc disease
• Carpal tunnel syndrome
• Metabolic derangement (ex,
hypoglycemia)
• Inner ear disease/BPV
• Transient global amnesia
• Cranial arteritis
Oxfordshire Community Stroke Project found that 62% of
patients referred by GP with a diagnosis of TIA were found to
have some other explanation for symptoms
(Dennis M, Stroke 1989)
Michael Ross, MD, FACEP
Is a “TIA” a TIA?
• Little agreement, even among neurologists
(kappa 0.25-0.65)
• Generally, neurologists are not the ones
making the diagnosis
– May even be less reproducibility
• Risk factors for stroke may identify true TIAs
Johnston et al, Neurology 2003; 60:280
Michael Ross, MD, FACEP
Utility of the H/P?
• TIA risk stratification
– Johnston criteria
– Rothwell criteria - “ABCD”
– Combination of the above = “ABCD2”
Michael Ross, MD, FACEP
TIA risk stratification - California Model
Johnston et al. Short-term prognosis after emergency department diagnosis of TIA.
JAMA. 2000;284:2901-6.
Independent risk factors for stroke:
• Age > 60yr
(OR = 1.8)
• Diabetes
(OR = 2.0)
• TIA > 10 min.
(OR = 2.3)
• Weakness with TIA (OR = 1.9)
• Speech impairment (OR = 1.5)
Risk factors were additive
Michael Ross, MD, FACEP
Our patient’s Johnston score?
Independent risk factors for stroke:
• Age > 60yr
0
• Diabetes
0
• TIA > 10 min.
1
• Weakness with TIA
1
• Speech impairment
1
stroke risk score of 3:
~5% at one week
~8% at 3 months
Michael Ross, MD, FACEP
TIA risk stratification - British model?
Rothwell,et al. Lancet 2005; 366: 29–36
• A = Age >60 years
• B = BP: SBP >140 or DBP >90
• C = Clinical:
– Unilateral weakness
– Speech disturbance
• D = Duration
– >60 min
– 10 – 59 min
– <10 min
= 1pt
= 1pt
= 2pt
= 1pt
= 2pt
= 1pt
= 0pt
Michael Ross, MD, FACEP
Michael Ross, MD, FACEP
Our patients ABCD score?
• A = Age >60 years
=0
• B = BP: SBP >140 or DBP >90
=0
• C = Clinical:
– Unilateral weakness
= 2pt
– Speech disturbance
= 1pt
• D = Duration
– >60 min
=0
– 10 – 59 min
= 1pt
– <10 min
=0
• TOTAL SCORE = 4 (5% risk of stroke at one week)
Michael Ross, MD, FACEP
ABCD2 Score
Michael Ross, MD, FACEP
ABCD2 Score
Score points for each of the following:
– Age >60 (1)
– Blood pressure >140/90 on initial evaluation (1)
– Clinical:
• Focal weakness (2)
• Speech impairment without weakness (1)
– Duration
• >60 min (2)
• 10-59 min (1)
– Diabetes (1)
Final Score 0-7
Michael Ross, MD, FACEP
ABCD2 Score Validation: Meta-analysis
Variable
Age >60 years
Diabetes mellitus
SBP >140 mmHg or DBP >90 mmHg
Duration 10-59 min vs. <10 min
Duration >60 min vs. <10 min.
Speech impairment without focal weakness
Focal weakness
No (%)
2-Day Risk
7-Day Risk
90-Day Risk
Odds Ratio
(95% CI)
Odds Ratio
(95% CI)
Odds Ratio
(95% CI)
3690 (76.7)
1.4 (1.0 -2.1)
1.4 (1.0 -2.0)
1.5
(1.2 -2.0)
797 (16.6)
1.6 (1.1 -2.2)
1.4 (1.1 -1.9)
1.7
(1.3 -2.1)
3420 (71.2)
2.1 (1.4 -3.1)
1.9 (1.4 -2.6)
1.6
(1.2 -2.0)
993 (20.7)
2.0 (1.0 -3.7)
1.9 (1.1 -3.3)
1.7
(1.1 -2.5)
2973 (61.9)
2.3 (1.3 -4.0)
2.6 (1.6 -4.3)
2.1
(1.5 -3.0)
899 (18.7)
1.4 (0.8 -2.3)
1.5 (1.0 -2.4)
1.7
(1.2 -2.3)
1979 (41.2)
2.9 (2.0 -4.3)
3.5 (2.5 -4.8)
3.2
(2.5 -4.1)
*All listed independent predictors were included in logistic regression analysis.
Michael Ross, MD, FACEP
ABCD2 Score and Stroke Risks
25%
Stroke Risk
20%
2-Day Risk
15%
7-Day Risk
30-Day Risk
10%
90-Day Risk
5%
0%
0
1
2
3
4
5
6
7
ABCD2 Score
Michael Ross, MD, FACEP
Prognosis Conclusions
• The ABCD2 Score stratifies short-term risk of stroke
after TIA
– 2-day risks
• Low Risk (34%):
• Moderate Risk (45%):
• Very High Risk (21%):
Score 0-3  1%
Score 4-5  4%
Score 6-7  8%
• “This rule is ready for clinical use”
– C. Johnston
Michael Ross, MD, FACEP
What is our patients’ ABCD2 score?
– Age >60
– Blood pressure >140/90 (initial) (1)
– Clinical:
• Focal weakness (2)
• Speech impairment without weakness (1)
– Duration
• >60 min (2)
• 10-59 min (1)
– Diabetes (1)
=0
=0
=2
=0
=0
=1
=0
• Total = 3
– Stroke at 2 days = 1%
– Stroke at 7 days = 2% (?!)
Michael Ross, MD, FACEP
Limitations of Prediction Rules
• Discriminatory value sub-optimal
– What about the patient with 90% carotid
stenosis and a low score???
• Generalizability seems poor (though exact
reasons for this unclear)
• Are these rules really just selecting patients
with “real” TIAs?
Michael Ross, MD, FACEP
2. HCT, ECG
• HCT - tumor, SDH,
NPH, etc
– Minor stroke and TIA
associated with a 10%
incidence of stroke on
MRI.
Michael Ross, MD, FACEP
Infarction in TIA
• Approximately 50% of those with
TIA have DWI changes on MRI
Kidwell et al Stroke 1999
Michael Ross, MD, FACEP
When is a “TIA” a TIA?
• What about when a clinically silent acute infarct is
present?
– New infarct on CT as a predictor of stroke:
• 38% with new infarct had a stroke within 90 days vs. 10% without
(p=0.008).
• OR 4.1 after adjustment for clinical factors.
– Recently, new infarct on MRI also shown to be a
predictor.
• 5-fold increase in risk with new lesion on baseline MRI
• Also, greater risk of in-hospital stroke in a second cohort.
VC Douglas et al, Stroke 2003; 34:2894
SB Coutts et al, Neurology 2005; 65:513
H Ay et al, Ann Neurol 2005; 57:679
Michael Ross, MD, FACEP
Recovery
Stroke
Neurologic
Deficit
Stroke?
TIA
Time
Michael Ross, MD, FACEP
90-day risk of stroke in patients with
a small stroke vs TIA?
Lancet Neurol 2006; 5: 323–31
Michael Ross, MD, FACEP
Reversible
ischemia
Infarction
Minor stroke
DWI+ TIA
TIA
Reversible ischemic
neurologic deficit
(RIND)
Stroke
Cerebral infarction
with transient signs
Michael Ross, MD, FACEP
2. HCT, ECG
• ECG – ATRIAL FIBRILLATION!!!
– Stroke risk – cardio-embolic risk
• 4.6% at 1 month
• 11.9% at 3 months
– 61% reduction in annual risk of stroke (both
ischemic or hemorrhagic) with coumadin
Michael Ross, MD, FACEP
3. Carotid Dopplers
Stroke risk depends on where the disease is:
7day 90day
CE = Cardio-Embolic:
2.5% 12%
LAA = Large arteries
4.0% 19%
Und = Undetermined
2.3% 9%
SVS = Small Vessels
0%
3%
Michael Ross, MD, FACEP
3. Carotid dopplers
The BIG question - WHEN???
• Carotid surgery if >70% stenosis
lesions is “time sensitive”.
• Stroke risk reduction if done within:
– 0-2 weeks
• 75% stenosis = 30.2%
– 2-4 weeks
• 75% stenosis = 17.6%
– 4-12 weeks
• 75% stenosis = 11.4%
– +12 weeks
• 75% stenosis = 8.9%
• Similar for 50-70% lesions
Michael Ross, MD, FACEP
Outpatient carotid dopplers?
Office management of TIA???
Goldstein et al. New transient ischemic attack and stroke: outpatient management by primary care physicians. Arch Intern Med.
2000;160:2941-6.
• Design:
– Retrospective study of 95 TIA and 81 stroke patients seen in
office
• Diagnostic testing within 30 days:
– 23% had head CT done
– 40% had carotid dopplers done
– 18% had ECG done
– 19% had echo done
– 31% had no other evaluation
Michael Ross, MD, FACEP
4. Further Clinical testing?
• Serial neurological
exams?
– 10.5% stroke within 3
months
• Half within 2 days
• Most within 1 day
• Monitoring for AF?
• 2-D echo?
Michael Ross, MD, FACEP
4. Further clinical testing
1
Strokes
Probability of Survival
.9
.8
Adverse Events
.7
.6
0
7
30
60
90
1480
1293
1451
1248
Days after TIA
No. of Patients
At Risk For:
St roke
Adverse Events
1001
1001
1577
1462
1527
1361
Johnston et al, JAMA 284:2901
5. Medical management
Antiplatelet Therapy
• Useful in non-cardioembolic causes
–Aspirin 50-325 mg/day
–Clopidogrel or ticlopidine
–Aspirin plus dipyridamole
•Latter two if ASA intolerant or if TIA while on ASA
• Routine anticoagulation not recommended
Michael Ross, MD, FACEP
5. Medical management
Risk Factor Management
•
•
•
•
•
•
•
HTN: BP below 140/90
DM: fasting glucose < 126 mg/dl
Hyperlipidemia: LDL < 100 mg/dl
Stop smoking!
Exercise 30-60 min, 3x/week
Avoid excessive alcohol use
Weight loss: < 120% of ideal weight
Michael Ross, MD, FACEP
Hospital Admission for TIA
• Medical management to minimize risk of
recurrent ischemia
• Expedite evaluation and treatment of
specific mechanisms – CEA for carotid
stenosis, anticoagulation for atrial fibrillation
• Observation for further events, with potential
expedited thrombolysis
• Avoid the lawyers
Michael Ross, MD, FACEP
Michael Ross, MD, FACEP
Management of TIA:
• Areas of Certainty:
– Need for ED visit, ECG, labs, Head CT
• Areas of less certainty
– The timing of the carotid dopplers
• Areas of Uncertainty - Johnston SC. N Engl J Med. 2002;347:1687-92.
– “The benefit of hospitalization is unknown. . .
Observation units within the ED. . . may
provide a more cost-effective option.”
Michael Ross, MD, FACEP
An Emergency Department Diagnostic Protocol
For Patients With Transient Ischemic Attack:
A Randomized Controlled Trial
To determine if emergency department TIA patients
managed using an accelerated diagnostic protocol
(ADP) in an observation unit (EDOU) will experience:
shorter length of stays
lower costs
comparable clinical outcomes
. . . relative to traditional inpatient admission.
Michael Ross, MD, FACEP
Patient population:
• Presented to the ED with symptoms of TIA
• ED evaluation:
– History and physical
– ECG, monitor, HCT
– Appropriate labs
– Diagnosis of TIA established
• Decision to admit or observe
• SCREENING AND RANDOMIZATION
Michael Ross, MD, FACEP
Methods:
ADP Exclusion criteria
•
•
•
•
•
•
•
•
•
•
•
Persistent acute neurological deficits
Crescendo TIAs
Positive HCT
Known embolic source (including a. fib)
Known carotid stenosis (>50%)
Non-focal symptoms
Hypertensive encephalopathy / emergency
Prior stroke with large remaining deficit
Severe dementia or nursing home patient
Social issues making ED discharge / follow up unlikely
History of IV drug use
Michael Ross, MD, FACEP
Methods:
ADP Interventions
• Four components:
– Serial neuro exams
• Unit staff, physician, and a neurology consult
– Cardiac monitoring
– Carotid dopplers
– 2-D echo
• BOTH study groups had orders for the same four
components
Michael Ross, MD, FACEP
Methods:
ADP Disposition criteria
• Home
– No recurrent deficits, negative workup
– Appropriate antiplatelet therapy and follow-up
• Inpatient admission from EDOU
– Recurrent symptoms or neuro deficit
– Surgical carotid stenosis (ie >50%)
– Embolic source requiring treatment
– Unable to safely discharge patient
Michael Ross, MD, FACEP
Results
Michael Ross, MD, FACEP
Results:
Patient Characteristics
Mean Age (sd)
Male n (%)
TIA Stroke Risk Factors - mean (sd) *
Median (IQR) Initial ED Length of Stay
* Johnston
Inpatient
Total
n=74
67.7yr
(15.4)
34
(46%)
2.7
(1.4)
6.2 hrs
(5.0-6.2)
TIA-ADP
Total
n=75
68.4yr
(15.3)
31
(41%)
2.4
(1.1)
5.7 hrs
(4.5-5.5)
- JAMA. 2000;284:2901-6.
Michael Ross, MD, FACEP
Results:
Performance of clinical testing
Inpatient
(n=74)
TIA-ADP
(n=75)
67
(90.5%)
25.2 hr
(17.3 – 37.1)
73
(97.3%)
13.0 hr
(8.4 – 18.0)
54
(73%)
43.0 hr
(23.8 – 63.8)
73
(97.3%)
19.1 hr
(16.7 – 22.5)
Carotid imaging
Number completed (n, %)
Time to completion
Echocardiography
Number completed (n, %)
Time to completion
Michael Ross, MD, FACEP
Results:
Length of Stay
Inpatient
ADP
Median
= 61.2 hr
= 25.6 hr
Difference
= 29.8 hr
(Hodges-Lehmann)
(p<0.001)
ADP sub-groups:
ADP - home = 24.2 hr
ADP - admit = 100.5 hr
Results:
90-Day Clinical Outcomes
90 Day Outcomes
Related return visits
Clinical Outcomes
Index visit CVA
Subsequent CVA (90 day)
Total 90 day CVA
Related Major event or MACE
Inpatient
Total
n=74
9 (12%)
TIA-ADP
Total
n=75
9 (12%)
5
2
7
(9%)
4
7
3
10
(13%)
4
Michael Ross, MD, FACEP
Results:
90 - day Costs
Inpatient
ADP
Median
= $1548
= $890
Difference
= $540
(Hodges-Lehmann)
(p<0.001)
ADP sub-groups:
ADP - home = $844
ADP - admit = $2,737
Study conclusion:
Compared to inpatient admission, the ED TIA
diagnostic protocol was:
• More efficient
• Less costly
• With comparable clinical outcomes
Michael Ross, MD, FACEP
Implications
• National feasibility of ADP:
– 18% of EDs have an EDOU
– 220 JCAHO stroke centers
• National health care costs
– Potential savings if 18% used ADP:
• $29.1 million dollars
– Medicare observation APC
• Impact of shorter LOS
– Patients – satisfaction, missed Dx . . .
– Hospitals – bed availability
Michael Ross, MD, FACEP
CLINICAL CASE - OUTCOME
• The patient was started on aspirin and admitted to the ED observation
unit.
• While in the unit she had a 2-D echo with bubble contrast, that was
normal. She had no arrhythmia detected on cardiac monitoring and no
subsequent neurological deficits.
• However, carotid dopplers were abnormal. She showed 30-50% stenosis
of the right internal carotid artery, and a severe flow limiting >70%
stenosis of the left carotid artery at the origin of the internal carotid
artery.
• She was admitted to the hospital for endarterectomy. Five days following
ED arrival, and following inpatient pre-operative clearance, she
underwent successful endarterectomy.
• On one month follow-up she was asymptomatic and her carotids were
doing well.
Michael Ross, MD, FACEP
Who do you send home
from the ED???
• C. Johnston:
– “TIA risk score does not identify a “zero” risk group”
– But it is a good start. . .
• Possibly:
– Negative ED work-up (ECG, exam, CT), low TIA score, negative
carotid dopplers within 6 months, safe home support for return in
next 48 hours if needed?
• Appropriate medications.
Michael Ross, MD, FACEP
Who do you send home
from the ED???
• Ron Krome:
– “It doesn’t matter what you do, as long as
you are right”
• If you are not sure, better play it safe. . .
– Admit or observe
Michael Ross, MD, FACEP
Conclusions
• TIAs are ominous
– Justifies acute interventions, including hospitalization
– Opportunity to prevent injury but trials are needed
• Recovery rather than complete resolution is likely the
important distinguishing characteristic and may identify
an unstable pathophysiology
• “TIAs” are heterogeneous
– Management should be individualized
– Prognostic scores may help
• Secondary prevention is critical
Michael Ross, MD, FACEP