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

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 Scores^{1-6,8,10,26,28,35,37,57,58}

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

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

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

1. Johnston SC, Fayad PB, Gorelick PB, et al. Prevalence and knowledge of transient ischemic attack among US adults. Neurology 2003;60(9):1429-1434.
2. Kleindorfer D, Panagos P, Pancioli A, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke 2005;36(4):720-723.
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.
6. Mozaffarian D, Benjamin EJ, Go AS, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation 2016;133:e38-e360.
7. Shah SH, Saver JL, Kidwell CS, et al. A multicenter pooled, patient-level data analysis of diffusion-weighted MRI in TIA patients. Stroke 2007;38:463.
8. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack. A scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke 2009;40(6):2276-2293.
9. Levy DE. How transient are transient ischemic attacks? Neurology 1988;38(5):674-677.
10. Mullen MT, Cucchiara BL. Redefinition of transient ischemic attack improves prognosis of transient ischemic attack and ischemic stroke: an example of the will rogers phenomenon. Stroke 2011 Dec;42(12):3612-3.
11. Nadarajan V, Perry RJ, Johnson J, et al. Transient ischaemic attacks: mimics and chameleons. Pract Neurol 2014;14:23-31.
12. Castle J, Mlynash M, Lee K, et al. Agreement regarding diagnosis of transient ischemic attack fairly low among stroke-trained neurologists. Stroke 2010;41:1367-1370.
13. Prabhakaran S, Silver AJ, Warrior L, et al. Misdiagnosis of transient ischemic attacks in the emergency room. Cerebrovasc Dis 2008;26:630-635.
14. Tsivgoulis G, Zand R, Katsanos AH, Goyal N, Uchino K, Chang J, et al. Safety of Intravenous Thrombolysis in Stroke Mimics: Prospective 5-Year Study and Comprehensive Meta-Analysis. Stroke 2015;46:1281-1287.
15. Dolmans LS, Rutten FH, El Bartelink ML, et al. Serum biomarkers for the early diagnosis of TIA: the MIND-TIA study protocol. BMC Neurol 2015;15:119.
16. Giles MF, Rothwell PM. Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol 2007;6:1063-1072.
17. Panagos PD. Transient ischemic attack (TIA): the initial diagnostic and therapeutic dilemma. American Journal of Emergency Medicine 2012;30:794-799.
18. Amarenco P, Lavallée PC, Labreuche J, Albers GW, Bornstein NM, et al.; TIAregistry.org Investigators. One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke. N Engl J Med 2016 Apr 21;374(16):1533-42.
19. Förster A, Gass A, Kern R, et al. Brain Imaging in Patients with Transient Ischemic Attack: A Comparison of Computed Tomography and Magnetic Resonance Imaging. European Neurology 2012;67(3):136-141.

20. Al-Khaled M, Matthis C, Munte TF, et al. Use of cranial CT to identify a new infarct in patients with a transient ischemic attack. Brain Behav 2012;2:377-381.
21. Douglas VC, Johnston CM, Elkins J, et al. Head computed tomography findings predict short-term stroke risk after transient ischemic attack. Stroke. 2003;34:2894-2899.
22. Sciolla R, Melis F, for the SINPAC Group. Rapid identification of high- risk transient ischemic attacks. Prospective validation of the ABCD score. Stroke. 2008;39:297-302.
23. Ay H, Oliveira-Filho J, Buonanno FS, et al. ‘Footprints’ of transient ischemic attacks: a diffusion-weighted MRI study. Cerebrovasc Dis. 2002;14(3-4):177-186.
24. Nah HW, Kwon SU, Kang DW, et al. Diagnostic and prognostic value of multimodal MRI in transient ischemic attack. Int J Stroke 2014;9:895-901.
25. Calvet D, Lamy C, Touze E, Oppenheim C, Meder JF, Mas JL. DWI lesions and TIA etiology improve the prediction of stroke after TIA. Stroke 2009;40(1):187-192.
26. Ay H, Gungor L, Arsava EM, et al. A score to predict early risk of recurrence after ischemic stroke. Neurology 2010;74(2):128-135.
27. Ay H, Arsava EM, Johnston SC, et al. Clinical-and Imaging-based Prediction of stroke risk after transient ischemic attack. The CIP model. Stroke 2009;40:181-186.
28. Bhatt A, Jani V. The ABCD and ABCD2 scores and the risk of stroke following a TIA: a narrative review. ISRN Neurology 2011;2011:1-12.
29. Edlow JA, Kim S, Pelletier AJ, et al. National study on emergency department visits for transient ischemic attack, 1992-2001. Acad Emerg Med 2006;13(6):666-672.
30. Ginde AA, Foianini A, Renner DM, et al. Availability and quality of computed tomography and magnetic resonance imaging equipment in U.S. emergency departments. Acad Emerg Med 2008;15(8):780-783.
31. Chalela JA, Kidwell CS, Nentwich LM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet 2007;369(9558):293-298.
32. Fiebach JB, Schellinger PD, Jansen O, et al. CT and diffusion-weighted MR imaging in randomized order: diffusion- weighted imaging results in higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke. Stroke 2002;33(9):2206-2210.
33. Mullins ME, Schaefer PW, Sorensen AG, et al. CT and conventional and diffusion-weighted MR imaging in acute stroke: study in 691 patients at presentation to the emergen- cy department. Radiology 2002;224(2):353-360.
34. Redgrave JN, Schulz UG, Briley D, Meagher T, Rothwell PM. Presence of acute ischaemic lesions on diffusion-weighted imaging is associated with clinical predictors of early risk of stroke after transient ischaemic attack. Cerebrovasc Dis 2007;24(1):86-90.
35. Purroy F, Begué R, Quílez A, Piñol-Ripoll G, Sanahuja J, Brieva L, et al. The California, ABCD, and unified ABCD2 risk scores and the presence of acute ischemic lesions on diffusion-weighted imaging in TIA patients. Stroke 2009 Jun;40(6):2229-32.
36. Purroy F, Pinol-Ripoll G, Quilez A, Sanahuja J, Brieva L, Suarez Luiz I. Validation of the ABCDI and ABCD2I scales in the registry of patients with transient ischemic attacks from Lleida (REGITELL) Spain. Med Clin (Barc) 2010 Sep 11;135(8):351-6.
37. Cucchiara BL, Messe SR, Taylor RA, Pacelli J, Maus D, Shah Q, Kasner SE. Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack? Stroke 2006 Jul;37(7):1710-4.
38. Asimos AW, Rosamond WD, Johnson AM, et al. Early diffusion weighted MRI as a negative predictor for disabling stroke after ABCD2 score risk categorization in transient ischemic attack patients. Stroke. 2009;40: 3252-3257.
39. Widjaja E, Manuel D, Hodgson TJ, et al. Imaging findings and referral outcomes of rapid assessment stroke clinics. Clin Radiol. 2005;60(10):1076-1082.
40. Carroll BA. Duplex sonography in patients with hemispheric 
 J Ultrasound Med. 1989;8(10):535-540.
41. Eliasziw M, Kennedy J, Hill MD, Buchan AM, Barnett JHM. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. CMAJ 2004;170(7):1105-1109.
42. Purroy F, Molina CA, Montaner J, Alvarez-Sabrin A. Absence of usefulness of ABCD score in the early risk of stroke of transient ischemic attack patients. Stroke 2007;38(3):8855-856.
43. Koton S, Rothwell PM. Performance of the ABCD and ABCD2 scores in TIA patients with carotid stenosis and atrial fibrillation. Cerebrovascular Diseases 2007;24(2-3):231-235.
44. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-453.
45. Rerkasem K, Rothwell PM. Carotid endarterectomy for symptomatic carotid stenosis (review). Cochrane Database Syst Rev 2011;(4): CD001081.
46. D’Onofrio M, Mansueto G, Faccioli N, Guarise A, Tamellini P, Bogina G, et al. Doppler ultrasound and contrast-enhanced magnetic resonance angiography in assessing carotid artery stenosis. Radiol Med (Torino) 2006;111(1):93-103.
47. Heijenbrok-Kal MH, Buskens E, Nederkoorn PJ, et al. Optimal peak systolic velocity threshold at duplex US for determining the need for carotid endarterectomy: a decision analytic approach. Radiology 2006;238:480-488.
48. Buskens E, Nederkoorn PJ, Buijs-Van Der Woude T, et al. Imaging of carotid arteries in symptomatic patients: cost-effectiveness of diagnostic strategies. Radiology 2004;233(1):101-112.
49. Nederkoorn PJ, Mali WP, Eikelboom BC, et al. Preoperative diagnosis of carotid artery stenosis. Accuracy of noninvasive testing. Stroke 2002;33:2003-2008.
50. Nonent M, Salem DB, Serfaty JM, et al. Overestimation of moderate carotid stenosis assessed by both Doppler US and contrast enhanced 3D-MR angiography in the CARMEDAS study. J Neuroradiol 2011;38:148-155.
51. Blakeley DD, Oddone EZ, Hasselblad V, et al. Noninvasive carotid artery testing. A meta-analytic review. Ann Intern Med 1995;122:360-367.
52. Nederkoorn PJ, van der Graaf Y, Hunink MG. Duplex ultrasound and magnetic resonance angiography compared with digital subtraction angiography in carotid artery stenosis. A systematic review. Stroke 2003;34:1324-1332.
53. Jahromi AS, Cina CS, Liu Y, et al. Sensitivity and specificity of color duplex ultrasound measurement in the estimation of internal carotid artery stenosis: a systematic review and meta-analysis. J Vasc Surg 2005;41:962-972.
54. Wardlaw JM, Chappell FM, Best JJ, et al, on behalf of the NHS Research and Development Health Technology Assessment Carotid Stenosis Imaging Group. Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis. Lancet 2006;367:1503-1512.
55. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22(8):983-988.
56. Elkins JS, Sidney S, Gress DR, et al. Electrocardiographic findings predict short-term cardiac morbidity after transient ischemic attack. Arch Neurol 2002;59(9):1437-1441.
57. Bray JE, Coughlan K, Bladin C. Can the ABCD Score be dichotomised to identify high-risk patients with transient ischaemic attack in the emergency department? EMJ 2007;24(2):92-95.
58. Lo BM, Carpenter CR, Hatten BW, Wright BJ, Brown MD, et al. Clinical Policy: Critical Issues in the Evaluation of Adult Patients With Suspected Transient Ischemic Attack in the Emergency Department. Ann Emerg Med 2016 Sep;68(3):354-370.e29.
59. Sanossian N, Ovbiagele B. The risk of stroke within a week of minor stroke or transient ischemic attack. Expert Opin Pharmacother 2008 Aug;9(12):2069-76.
60. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007;369:283-292.
61. Nguyen H, Kerr D, Kelly AM. Comparison of prognostic performance of scores to predict risk of stroke in ED patients with transient ischaemic attack. Eur J Emerg Med. 2010;17:346-348.
62. Tsivgoulis G, Spengos K, Manta P, Karandreas N, Zambelis T, Zakopoulos N, Vassilopoulos D. Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study. Stroke 2006 Dec;37(12):2892-7.
63. Fothergill A, Christianson TJ, Brown RD, Rabinstein AA. Validation and Refinement of the ABCD2 Score: a population-based analysis. Stroke; a journal of cerebral circulation. 2009;40(8):2669-2673.
64. Josephson SA, Sidney S, Pham TN, Bernstein AL, Johnston SC. Higher ABCD score predicts patients most likely to have true transient ischemic attack. Stroke 2008;29(11):3096-3098.
65. Sanders LM, Srikanth VK, Blaker DJ, et al. Performance of the ABCD2 score for stroke risk post TIA: meta-analysis and probability modeling. Neurology 2012;79:971-980.
66. Giles MF, Rothwell PM. Systematic review and pooled analysis of published and unpublished validations of the ABCD and ABCD2 transient ischemic attack risk scores. Stroke 2010;41:667-673.
67. Giles MF, Albers GW, Amarenco P, et al. Addition of brain infarction to the ABCD2 Score (ABCD2I): a collaborative analysis of unpublished data on 4574 patients. Stroke 2010;41(9):1907–13.
68. Harrison JK, Sloan B, Dawson J, Lees KR, Morrison DS. The ABCD and ABCD2 as predictors of stroke in transient ischemic attack clinic outpatients: a retrospective cohort study over 14 years. QJM 2010;103:679-685.
69. Schrock JW, Victor A, Losey T. Can the ABCD2 risk score predict positive diagnostic testing for emergency department patients admitted for transient ischemic attack? Stroke. 2009 Oct;40(10):3202-5.
70. Amarenco P, Labreuche J, Lavallee PC, et al. Does ABCD2 score below 4 allow more time to evaluate patients with a transient ischemic attack? Stroke 2009;40:3091–3095.
71. Chandratheva A, Geraghty OC, Luengo-Fernandez R, et al; for the Oxford Vascular Study. ABCD2 score predicts severity rather than risk of early recurrent events after transient ischemic attack. Stroke 2010;41:851-856.
72. Chatzikonstantinou A, Wolf ME, Schaefer A, et al. Risk prediction of subsequent early stroke in patients with transient ischemic attacks. Cerebrovasc Dis 2013;36:106-109.
73. Purroy F, Jimenez Caballero PE, Gorospe A, et al; on behalf of the Stroke Project of the Spanish Cerebrovascular Diseases Study Group. Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores. Cerebrovasc Dis 2012;33:182-189.
74. Kiyohara T, Kamouchi M, Kumai Y, Ninomiya T, Hata J, Yoshimura S, et al. ABCD3 and ABCD3-I scores are superior to ABCD2 score in the prediction of short- and long-term risks of stroke after transient ischemic attack. Stroke 2014 Feb;45(2):418-25.
75. Perry JJ, Sharma M, Sivilotti MLA, et al. Prospective validation of the ABCD2 score for patients in the emergency department with transient ischemic attack. CMAJ : Canadian Medical Association Journal 2011;183(10):1137-1145.
76. Stead LG, Suravaram S, Bellolio MF, et al. An Assessment of the Incremental Value of the ABCD2 Score in the Emergency Department Evaluation of Transient Ischemic Attack. Annals of emergency medicine 2011;57(1):46-51.
77. Ghia D, Thomas P, Cordato D, Epstein D, Beran RG, Cappelen-Smith C, et al. Low positive predictive value of the ABCD2 score in emergency department transient ischaemic attack diagnoses: the South Western Sydney transient ischaemic attack study. Intern Med J 2012 Aug;42(8):913-8.
78. Perry JJ, Sharma M, Sivilotti ML, et al. A prospective cohort study of patients with transient ischemic attack to identify high-risk clinical characteristics. Stroke 2014;45:92-100.
79. Wardlaw JM, Brazzelli M, Chappell FM, et al. ABCD2 score and secondary stroke prevention: meta-analysis and effect per 1,000 patients triaged. Neurology 2015;85(4):373–80.
80. Stead LG, Bellolio MF, Suravaram S, Brown Jr RD, Bhagra A, Gilmore RM, et al. Evaluation of transient ischemic attack in an emergency department observation unit. Neurocrit Care 2009;10:204-8.
81. Hörer S, Schulte-Altedorneburg G, Haberl RL. Management of patients with transient ischemic attack is safe in an outpatient clinic based on rapid diagnosis and risk stratification. Cerebrovasc Dis 2011;32(5):504-10.
82. Engelter ST, Amort M, Jax F, et al. Optimizing the risk estimation after a transient ischaemic attack – the ABCDE+ score. Eur J Neurol 2012;19(1):55-61.
83. Sorensen AG, Ay H. Transient ischemic attack: definition, diagnosis, and risk stratification. Neuroimaging Clin N Am. 2011;21(2):303-313.
84. Oostema JA, DeLano M, Bhatt A, et al. Incorporating diffusion-weighted magnetic resonance imaging into an observation unit transient ischemic attack pathway: a prospective study. Neurohospitalist. 2014;4:66-73.
85. Ross MA, Compton S, Medado P, et al. An emergency department diagnostic protocol for patients with transient ischemic attack: a randomized controlled trial. Ann Emerg Med. 2007;50: 109-119.
86. SPS3 Investigators; Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367(9):817-825.
87. Mijalski C, Silver B. TIA management: should TIA patients be admitted? Should TIA patients get combination antiplatelet therapy? Neurohospitalist 2015;5(3): 151–60.
88. Lavalle ́e P, Meseguer E, Abboud H, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007;6(11):953-960.
89. Olivot JM, Wolford C, Castle J, et al. Two aces. Transient ischemic attack work-up as outpatient assessment of clinical evaluation and safety. Stroke. 2011;42:1839-1843,
90. Wasserman J, Perry J, Dowlatshahi D, et al. Stratified, urgent care for transient ischemic attack results in low stroke rates. Stroke. 2010;41(11):2601-2605.
91. Martinez-Martinez MM, Martinez-Sanchez P, Fuentes B, et al. Transient ischaemic attacks clinics provide equivalent and more efficient care than early in-hospital assessment. Eur J Neurol 2013;20:338-343.
92. Sanders LM, Srikanth VK, Jolley DJ, et al. Monash transient ischemic attack triaging treatment. Safety of a transient ischemic attack mechanism-based outpatient model of care. Stroke. 2012;43:2936-2941.
93. Webster F, Saposnik G, Kapral MK, Fang J, O’Callaghan C, Hachinski V. Organized outpatient care: stroke prevention clinic referrals are associated with reduced mortality after transient ischemic attack and ischemic stroke. Stroke. 2011 Nov; 42(11):3176-82.
94. Wu CM, Manns BJ, Hill MD, Ghali WA, Donaldson C, Buchan AM. Rapid evaluation after high-risk TIA is associated with lower stroke risk. Can J Neurol Sci. 2009 Jul; 36(4):450-5.
95. Kraaijeveld CL, van Gijn J, Schouten HJ, et al. Interobserver agreement for the diagnosis of transient ischemic attacks. Stroke 1984;15(4):723-725.
96. Tomasello F, Mariani F, Fieschi C, et al. Assessment of inter-observer differences in the Italian multicenter study on reversible cerebral ischemia. Stroke 1982;13(1):32-35.
97. Landi G. Clinical diagnosis of transient ischaemic attacks. Lancet 1992;339(8790):402-405.