Current Controversies in TIA Evaluation

Author: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

A 58-year-old male with a history of coronary artery disease, hypertension, and diabetes presents after experiencing right arm weakness for less than one hour. The symptoms resolved with no further episodes. This has never happened before and frightened him. His initial vital signs reveal mild hypertension, with a completely normal neurologic exam including cranial nerves, motor, sensory, cerebellar, gait, and reflexes. ECG, head CT, and labs are unrevealing. You diagnose him with TIA, but what now? Does he need further testing? Does he require admission?

Transient ischemic attack (TIA) affects over 200,000 U.S. patients per year, which increases with age.1-3 TIA may precede 14% to 23% of strokes.3-8 The risk of stroke after TIA may be as high as 10% at 7 days and 17% at 90 days.1-8 Due to this risk and the mortality and morbidity from stroke, TIA requires management and evaluation for high risk conditions such as atrial fibrillation and carotid stenosis.

TIA was previously defined as a transient neurologic deficit with symptom resolution in less than 24 hours. The American Heart Association (AHA) updated definition includes a brief neurologic deficit due to cerebral ischemia, with no permanent infarction.3-9 No time restriction is present in the new definition. Up to 30% to 50% of patients diagnosed with TIA have infarction on neuroimaging, which is one of the reasons the definition was changed.7,9 Symptoms associated with transient ischemia resolve within one hour in 60% of patients and 2 hours in 70%.7-9 This updated definition increases the annual rate of ischemic stroke by 50,000 annually, while decreasing the 90 day stroke rate in those diagnosed with TIA.10

Significant variation exists in ED imaging, laboratory investigation, and disposition.16,17 Historically, patients have been admitted for evaluation of suspected TIA.  A study by Johnson et al. demonstrated 5% of patients with TIA go on to have stroke within 2 days, with 10% suffering acute stroke within 3 months.1 However, a 2016 study found a stroke rate of 2.1% at 7 days and 6.2% at one year.18 The American Heart Association (AHA) and National Stroke Association (NSA) possess several criteria for which patients require admission:3-6,8

AHA and NSA Recommendations

Association Admission Criteria
AHA ABCD2 score of > 3, ABCD2 score of 0-2 and uncertain follow up, or ABCD2 score of 0-2 and evidence that focal ischemia occurred.
NSA Consider admission if first TIA within 24-48 hours. For recent TIA within one week, hospitalization is needed for crescendo TIA (worsening TIA’s), duration of symptoms longer than 1 hour, internal carotid stenosis greater than 50% with symptoms, known cardiac source of embolus, or hypercoagulable state.

Assessment of patients with suspected TIA should be conducted in a rapid manner, and this evaluation of TIA can also determine patient disposition. Several factors associated with higher stroke risk include age over 60 years, infarct discovered on imaging, cardiogenic emboli, and modified Rankin score greater than 2.1,2,16-18 The evaluation of suspected TIA centers on neuroimaging and the use of clinical risk scores for risk stratification. The specific imaging required in the ED and patient disposition based on risk scores are controversial topics.

Imaging

Neuroimaging within 24 hours of suspected TIA is recommended by the AHA/ASA, and MRI with DWI is preferred.3-6,8 CT is most commonly available in the ED, as 56% to 92% of patients receive imaging with this modality in the ED.19

Head CT

Head CT noncontrast can rapidly identify other conditions and is the primary ED modality, with sensitivities ranging from 12% to 52%.3-6,8,17,19-21 Forster et al. in 2012 finds 95.7% of initial head CT examinations are negative for acute infarction.19 A study from Germany evaluating head CT noncontrast in 1533 patients with suspected TIA finds a 3.1% rate of acute CVA, despite complete resolution of symptoms.20 Another study in 2003 finds the frequency of stroke does not differ at 90 days in those receiving head CT versus those who do not.21 This same study does endorse the use of CT to evaluate for other etiologies of symptoms, as 1.2% of patients have an alternative condition found on head CT.21

MRI

The best test is magnetic resonance imaging (MRI) in acute ischemic stroke and TIA evaluation, specifically the use of MRI with diffusion-weighted imaging (DWI). This modality has a Class I, Level B recommendation for suspected TIA.6,8 DWI will demonstrate hyperintense signals due to cytotoxic edema.23-25 One third of patients with normal CT and MRI noncontrast demonstrate acute lesions on DWI.23 Close to 39% of patients have ischemic lesions on imaging, and follow-up scanning past 24 hours reveals involvement in up to 100% of patients.24,25 Ischemic lesions on MRI predict future stroke (up to fifteen-fold increase).26-28

This test may not be available in the ED (available in 15% of centers at any one time).29,30 MRI displays greater diagnostic capabilities for ischemic lesions than CT, as 35.2% of patients with negative CT display ischemic lesions on MRI.19 Within 12 hours of acute stroke symptom onset, MRI with DWI demonstrates odds ratio (OR) of 25 (95% CI 8-79) if ischemia is found, while another study finds an OR 10.1 for acute stroke within 7 days with positive DWI.23,24,27,28  Sensitivity ranges from 83% to 97% for early ischemia.31-33 Stroke risk in negative DWI ranges from 0 to 2.9% at 2 and 7 days, while patients with scans positive for ischemia possess a stroke rate of 14.3% at 2 days and 23.8% at 7 days.23,27,31-37 However, intermediate to high risk scores from clinical rules are not associated with abnormalities found on DWI.34-36

Patients with positive DWI remain at high risk for stroke, no matter the predicted risk on clinical scoring. Calvet et al. found positive DWI in 40% of patients, and factors associated with positive imaging included weakness, duration of symptoms greater than 60 minutes, atrial fibrillation, and large artery atherosclerosis.28 Negative MRI with DWI is associated with low risk of stroke, especially when used in conjunction with risk stratification.25,27,28,38 Asimos et al. found patients with negative MRI and low ABCD2 are extremely low risk for stroke.38

Vascular Imaging

A major risk for stroke and recurrent TIA includes significant carotid stenosis (occlusion greater than 70% and greater than 50% with symptoms in males).5 The AHA/ASA provides a Class 1, Level A recommendation for intracranial and extracranial vascular imaging in evaluation of suspected TIA.3-5,8 Up to 31% of patients with TIA have carotid disease, and in the setting of significant disease, 90 day stroke risk can reach 20.1%.39,40-43  Carotid disease alone is a significant risk factor for adverse outcome including recurrent stroke, with a hazard ratio (HR) of 4.9.25 Close to half of patients with positive lesions on DWI have significant stenosis of at least one large intra/extracranial vessel.25

Noninvasive testing includes carotid ultrasound, CTA, and magnetic resonance angiography (MRA).44-46 Negative likelihood ratio (LR) for MRA and US is 0.07.47 US sensitivity ranges from 70% to 90%, MRA sensitivity 82% to 94%, and CTA sensitivity 77% to 90%.49-54 Literature suggests that stenosis less than 50% on Doppler US or MRA is associated with low likelihood of significant disease. However, stenosis greater than 50% requires further imaging with MRA or CTA.3-6,8,51-54

Doppler US and MRA possess adequate sensitivity and specificity for diagnosis of significant carotid disease. CTA is likely easier to obtain in most emergency departments, but this test alone may miss significant disease.

Atrial Fibrillation

Atrial fibrillation is a major risk factor for stroke, independent of imaging and risk prediction tools.3-6,8,55 Close to 2% of patients with TIA will be diagnosed with new onset atrial fibrillation.55,56  Risk scores, including the ABCD and ABCD2 scores, are not correlated with atrial fibrillation.57 The diagnosis and acute management of atrial fibrillation including anticoagulation may reduce short and long-term risk of stroke.3-6,8

Risk Scores

Providers have sought tools to predict stroke risk after TIA, shown in Table 2.1-6,8,10,26,28,35,37,57,58 Risk stratification tools may identify patients at low risk for whom further workup may be deferred, while identifying patients at short and long term risk of stroke.

Table 2 – Clinical Risk Scores1-6,8,10,26,28,35,37,57,58

Prediction Rule Components Points
California rule Age > 60 years

Diabetes

Unilateral weakness

Impaired speech

Symptoms > 10 minutes

Total

1

1

1

1

1

5

ABCD rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)

Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes

Total

1

1

2

1

2

1

1

6

ABCD2 rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)

Diabetes

Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes

Total

1

1

1

2

1

2

1

1

7

ABCD3 rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)

Diabetes

Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes

Dual TIA

Total

1

1

1

2

1

2

1

1

2

9

ABCD3-I rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)

Diabetes

Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes

Dual TIA

Positive imaging (Internal carotid stenosis > 50%, DWI)

Total

1

1

1

2

1

2

1

1

2

2

11

One of the first evaluations for stroke risk is the ABCD score, shown above.1,16,22,35-37,58-66 Patients with score 0-3 are considered low risk, while those greater than 3 points are considered moderate to high risk. Low risk scores demonstrate 2-day, 7-day, 30-day, and 90-day risks of 1.2%, 5.9%, 5.4%, and 3.2%, respectively, with the moderate to high risk patients demonstrating risks of 4.9-7.9%, 4.2-15.9%, 6.9-17.6%, and 11.3-18.9%, respectively.1,22,60-66 The California rule is similar to the ABCD score. However, it does not use hypertension, but diabetes.1,22,35,58,60,61 Both the ABCD and California scores categorize over 54% to 85% as at least intermediate risk.1,16,22,35-37,58-66 The ABCD and California scores demonstrate AUC curves of 0.62 to 0.81, with the majority of studies demonstrating values of less than 0.70.28,58,69 This value correlates with fair accuracy for predicting stroke in these patients, but the scores place a significant number of patients at or above intermediate risk.

The most commonly used tool is the ABCD2 score, which adds diabetes. Initial studies validating this score suggest strong predictive attributes for stroke risk at 24 hours.58,60,64,65,69 Using this score for stratification, 33%, 48%, and 19% are categorized as low, moderate, and high risk, respectively.27,28,35,58,60,61,63-75 The score demonstrates sensitivities of 86% in moderate to high risk patients, with specificity 35%. Close to 1% of this group experience stroke at 2 days, with 1.2% at 7 days. AUC is 0.66-0.74 for 2 and 7 day stroke risk. Initial results show stroke occurs in 3.2% of patients at 90 days. However, positive likelihood ratios never reach higher than 1.54.28,35,58,63-75

These scores demonstrate limited predictive ability. Schrock et al. in 2009 suggests high risk ABCD2 score is not beneficial for guidance on obtaining other diagnostic testing including MRI, ECG, head CT.58,69 Perry et al. suggests it is not a reliable tool, as a cutoff of 5 points results in misclassification of approximately 8% of patients as low risk.75 This cutoff displays a sensitivity of 94.7%, but a specificity of 12.%.75 Stead et al. in 2011 finds no difference between different classifications based on the ABCD2 score, as the low, moderate, and high risk groups display stroke rates of 1.1%, 0.3%, 2.7% at 7 days.75 A study by Ghia in 2012 finds stroke rates in low risk ABCD2 patients to be 1.2% at 30 days and 0.8% in moderate and high risk groups, questioning ability for risk stratification and stroke prediction.77

An Australian study suggests patients in all risk categories possess similar stroke rates, while at the same time having poor predictive ability.28,58,65,77 When used in combination with other imaging modalities evaluating the brain and carotid systems, the ABCD2 score does not provide additional risk stratification information, with sensitivity in high risk patients only 30% to 40%.65,69,70,71,75-77 Schrock et al. suggests the use of this test alone misses patients with high grade carotid stenosis.69 A 2012 meta-analysis of 33 studies finds a positive likelihood ratio of 1.4 for scores > 3, with sensitivities of 89% at days 2 and 7 and 87% at day 90 post TIA.65 This score does not have predictive capability likely to change management in the ED.65

Can you add imaging? The ABCD2-I score added CT or MRI with DWI, which results in an AUC value of 0.78 at 7 days, versus 0.66 for the original ABCD2 score.67 The ABCD3-I score, has a third “D” representing a TIA occurring within one week of the first TIA.74 The “I” component refers to carotid stenosis greater than 50% discovered on carotid imaging or any abnormality discovered on MRI with DWI. It does demonstrate better ability when compared to the original ABCD2 score.28,58,74 The C-statistic for the modified score is 0.66, while the ABCD2 score demonstrates a C-statistic of 0.54, neither over the threshold of 0.7 for moderate prediction. When imaging involves MRI with DWI, this values reaches 0.81.28,58,74,75

Another rule is the Canadian TIA Score.  Scores range from -3 to 23, and stroke rate within 7 days ranges from 0.01% to greater than 27%. Patients with less than 6 points demonstrate less than 1% chance of stroke, with sensitivity approaching 98%. Scores greater than 10 demonstrate 5.1% stroke risk, with scores greater than 12 possessing a 12.6% risk. The discriminatory capability of this test possesses a C-statistic of 0.77.78 However, this score requires multiple variables and has not been validated.

Table 3 – Canadian TIA Score78

Item Points
Clinical Findings

First TIA (in lifetime)

Symptoms > 10 min

History of carotid stenosis

Already on antiplatelet therapy

History of gait disturbance

History of unilateral weakness

History of vertigo

Initial diastolic blood pressure > 110 mm Hg

Dysarthria or aphasia

 

Investigations in the ED

Atrial fibrillation on ECG

Infarction on CT (new or old)

Platelet count > 400×109/L

Glucose > 15 mmol/L

Total score (-3 to 23)

 

2

2

2

3

1

1

-3

3

1

 

 

2

1

2

3

 

Role of Risk Scores

The use of prediction scores alone for risk stratification is not recommended, as they are not reliable.58,65,69,75,77 Over 40% of patients with greater than 4 on the ABCD2 score are experiencing mimic.37 Scores do not allow recognition of stroke subtype such as lacunar, cardioembolic, or large vessel or the specific vascular territory affected.58,65,69,75,77 MRI with DWI and clinical features may predict risk. Cucchiara et al. finds scores 0-3 have significant risk of stroke (up to 20%).37 Close to 1/3 of patients in the ED are not categorized appropriately into low, intermediate, or high risk.76,80 Risk scores are a tool that may assist in gauging short term risk of stroke, but this should not take precedence over physician gestalt.4-8,58

The combination of MRI with risk stratification significantly improves the diagnostic and predictive values of the provider. The addition of MRI with DWI to the ABCD2 score possesses a higher 7 day stroke risk prognostic ability after TIA.26-28,38,58 One study demonstrates the absence of lesion on MRI with DWI and ABCD < 4 reaches 100% sensitivity for excluding stroke at 7 days, while those with infarction on imaging show a 20-fold increase in stroke risk.38

ED Directed Protocols and Observation Units

ED diagnostic protocols and observation units can reduce length of stay and total cost, while improving patient compliance with AHA and NSA recommended treatments.3-8,58,80-85 Studies demonstrate faster time to risk stratification and treatment, as well as a significant reduction in stroke from 10% to approximately 1 to 2% with use of these clinics.85-87

Stead et al. evaluated TIA patients in an ED unit, with the use of a standardized protocol including patients with no symptoms and negative head CT noncontrast.80 This study finds approximately 30% of patients can be discharged directly from an observation unit, with no difference in rate of strokes at 2 and 7 days.80 Ross et al. in 2007 evaluated 149 patients with suspected TIA in the ED with a diagnostic protocol with carotid imaging, echocardiography, repeat neurologic examination, and cardiac monitoring for a period of at least 12 hours.85 No increase in adverse outcomes are present in those patients in the protocol, as well as shorter length of stay and total cost in the observation patients.85 Oostema et al. investigated an ED observation unit that combined the use of MRI with DWI and a diagnostic protocol.84 In this study, 94% of patients underwent MRI with DWI, and 97% of patients in the accelerated protocol underwent imaging of the cervical vessels. Close to 14% of patients have infarct on DWI, and these patients demonstrate a 6.3% risk of stroke at 30 days compared to 1.2% in patients with negative DWI.84

How about an outpatient clinic? Mijalski in the OTTAWA trial obtained ECG and head CT in the ED, followed by carotid Doppler, echocardiogram, 24 hours telemetry, and neurology follow up.87 This study found a 2 day stroke rate with use of this clinic of 1%, with a 3.2% risk at 90 days.87 Lavallee et al. finds a 90 day stroke rate of 1.24% in patients managed in a hospital-based clinic staffed with neurologists, with imaging including MRI or head CT, carotid ultrasound, ECG, and ankle-brachial index (ABI).81,88 Close to 74% of patients can be evaluated and discharged upon presentation to the ED with the use of this clinic.88 Olivot et al. discharged patients with ABCD2 scores of 0 to 3 to an outpatient TIA clinic, while patients with scores of 4 or 5 underwent imaging of the intracranial and carotid vasculature.89 Approximately 70% of patients can be discharged from the ED in this study to follow-up at the TIA clinic, with low stroke rate.89 Wasserman et al. evaluated 982 patients, with 32% categorized as low risk, 49% as medium risk, and 19% as high risk.90 All patients underwent head CT and ECG in the ED and follow-up care in a stroke clinic where they received carotid Doppler, echocardiogram, and laboratory testing. Stroke rate was less than 1% risk for those with scores 0-4.90

Stroke rate at 90 days can be reduced by 80% with the use of these diagnostic protocols or dedicated clinics.90-94 This requires an ED system with resources available including a protocol or TIA clinic.58

What should the EM provider do?

A summary of the 2016 ACEP clinical policy on TIA is below, released in 2016.58

American College of Emergency Physicians Recommendations for TIA58

Question Recommendation Level
In adult patients with suspected TIA, are there clinical decision rules that can identify patients at very low short-term risk for stroke who can be safely discharged from the ED? In adult patients with suspected TIA, do not rely on current existing risk stratification instruments (eg, ABCD2 score) to identify TIA patients who can be safely discharged from the ED. B
In adult patients with suspected TIA, what imaging can be safely delayed from the initial ED workup? (1) The safety of delaying neuroimaging from the initial ED workup is unknown. If noncontrast brain MRI is not readily available, it is reasonable for physicians to obtain a noncontrast head CT as part of the initial TIA workup to identify TIA mimics (eg, intracranial hemorrhage, mass lesion). However, noncontrast head CT should not be used to identify patients at high short-term risk for stroke.

(2) When feasible, physicians should obtain MRI with DWI to identify patients at high short-term risk for stroke.

(3) When feasible, physicians should obtain cervical vascular imaging (carotid ultrasonography, CTA, or MRA) to identify patients at high short-term risk for stroke.

C
In adult patients with suspected TIA, is carotid ultrasonography as accurate as neck CTA or MRA in identifying severe carotid stenosis?

 

In adult patients with suspected TIA, carotid ultrasonography may be used to exclude severe carotid stenosis because it has accuracy similar to that of MRA or CTA. C
In adult patients with suspected TIA, can a rapid ED-based diagnostic protocol safely identify patients at short-term risk for stroke? In adult patients with suspected TIA without high-risk conditions,* a rapid ED- based diagnostic protocol may be used to evaluate patients at short-term risk for stroke.

*High-risk conditions include abnormal initial head CT result (if obtained), suspected embolic source (presence of atrial fibrillation, cardiomyopathy, or valvulopathy), known carotid stenosis, previous large stroke, and crescendo TIA.

B

Patients should be evaluated within 24 hours from the time of event, whether as inpatient, in an ED observation unit/diagnostic protocol, or specialized outpatient TIA clinic. A detailed and accurate history is important, as misdiagnosis by emergency providers occurs in close to 60% of cases.12,13,28,95,96 The provider should assess for focal neurologic symptoms. Symptoms associated with loss of function such as motor weakness, altered speech, or vision abnormalities suggest TIA, while symptoms including tingling, increased speech, involuntary motions, and flashing lights suggest alternative diagnosis.11-13,97 An ECG should be obtained to evaluate for atrial fibrillation. MRI with DWI is the first line modality per the AHA/ASA.3-8 However, in most emergency departments, head CT noncontrast is rapidly available at all times. Any focal lesion found on neuroimaging warrants admission.2-8,28,58

Patient assessment and availability of local resources will determine the disposition. Admission criteria include crescendo neurologic symptoms or continued symptoms, atrial fibrillation on ECG, vascular disease on imaging, ischemic focus on neuroimaging, poor social situation, inability to follow-up, and poor compliance. 2-8,28,58 If these are not present, a rapid diagnostic protocol or rapid follow-up clinic can be beneficial. MRI with DWI and carotid imaging are cornerstones of evaluation. Evaluation with these studies should occur within 24 hours. ED-focused diagnostic protocols and rapid follow-up clinics decrease stroke risk and patient cost. Stratification tools may be used in conjunction with neuroimaging such as MRI with DWI, but these scores alone do not sufficiently identify patients at low-risk for stroke.

 

Summary

– TIA is defined as a brief episode of neurologic dysfunction with no permanent infarction. Over 200,000 patients per year in the U.S. are affected, and this disease may precede approximately 20% of strokes.

– Patients are typically admitted for inpatient management due to this risk of future stroke. A great deal of literature has evaluated the use of imaging, clinical risk scores, and diagnostic protocols in the evaluation of TIA.

– Head CT noncontrast is not reliable for acute ischemia, but it can find alternative conditions necessitating management. MRI with DWI displays greater diagnostic ability. Carotid imaging includes MRA, CTA, and Doppler with US. MRA and Doppler US demonstrate similar test characteristics.

– Risk scores that predict future stroke are not reliable when used alone.

– The use of ED diagnostic protocols and observation units can reduce length of stay while improving patient treatment and reducing stroke rate.

– Careful evaluation of risk factors and imaging may allow the patient to be discharged with follow up within 24 hours for further evaluation.

 

References/Further Reading

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  3. Kernan WN, Ovbiagele B, Black HR, et al. American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160-2236.
  4. Sacco RL, Kasner SE, Broderick JP, et al. American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:2063-89.
  5. Jauch EC, Saver JL, Adams HP Jr, et al, American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870–947.
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