Minor Stroke and Transient Ischemic Attack: Research and Practice
- 1Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI, USA
- 2Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University, Providence, RI, USA
- 3Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI, USA
- 4Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA
A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA.
In population-based studies, approximately two-thirds of ischemic stroke patients have mild deficits (1, 2). Minor stroke is generally defined as an National Institute of Health Stroke Scale (NIHSS) of 5 or less, which takes into account certain deficits but not the fact that some can have a more profound impact on quality of life than others. Hence, the scale does not linearly correlate deficit and disability. While studies suggest using an NIHSS of 3 or less to define minor stroke (3, 4), real-world definitions of non-disabling deficits are largely dependent on clinical judgment, which has been shown to vary widely among physicians (5). Transient ischemic attack (TIA) has a more widely accepted definition that includes focal neurological symptoms lasting for <24 h without the presence of infarction on diffusion-weighted imaging (6).
In clinical practice, both minor stroke and TIA patients undergo similar diagnostic evaluations. Due to the relatively high early risk of stroke recurrence in both groups and disability in minor stroke patients, key decisions in the management of minor strokes and TIA can have significant impacts on clinical outcomes, quality of life, and cost of care. In this review, we summarize the current research on minor stroke and TIA, and highlight key points in acute treatment and secondary stroke prevention strategies.
Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (IV rtPA) is an important treatment for patients with acute ischemic stroke (7). Patients with minor deficits are often excluded from such treatment even though they demonstrate a high rate of suboptimal functional outcome. While retrospective studies show no benefit in 3-month outcome between thrombolysed and non-thrombolysed patients with mild deficits (8, 9), these studies are subject to selection bias in favor of treating patients with disabling versus non-disabling deficits. Recent evidence from a stroke registry supports the use of IV rtPA compared with routine medical management in patients with mild deficits (10). In addition, a post hoc analysis of the International Stroke Trial-3 (IST-3) found that patients with mild deficits who were treated IV rtPA compared to placebo had a favorable shift in the Oxford Handicap Scale distribution (adjusted odds ratio, 2.38; 95% confidence interval, 1.17–4.85). The most feared complication of IV rtPA is symptomatic intracerebral hemorrhage (sICH), which is seen in up to 2% of patients with minor stroke (11–13). Due to the fear of hemorrhagic complications, physicians tend to offer IV rtPA to patients who they consider to have a disabling deficit, a highly subjective clinical judgment. The subjectivity of this approach highlights the need for prospective cohorts to better understand the natural history and predictors of long-term functional and cognitive outcomes in patients with minor stroke, taking into account the type of deficit, the patient, and potential for stroke recovery. Two randomized clinical trials comparing IV rtPA versus placebo in patients with minor non-disabling deficits are underway (14, 15).
Acute Endovascular Therapy
Several clinical trials recently showed that the addition of mechanical thrombectomy to best medical treatment in patients with acute ischemic stroke and evidence of a large artery occlusion resulted in significant improvement in long-term functional outcomes (16). Most of these studies excluded patients with minor stroke leading to variability in the use of mechanical thrombectomy for patients with acute large vessel occlusion and transient or minor deficits. Large vessel occlusion is an important and consistent predictor of neurological deterioration and disability in patients with minor stroke (17, 18). Excluding these patients from endovascular treatment may lead to a sevenfold increased risk of long-term disabling deficits and up to 50% of patients being functionally disabled at 3 months (17, 18). Recent AHA/ASA guidelines suggest that it is reasonable to consider endovascular treatment for patients with an NIHSS score <6 and evidence of large vessel occlusion. However, clinical trials are needed to prove the efficacy of endovascular treatment in this patient population (19).
Risk of Recurrent Stroke
The risk of recurrent stroke in patients with minor stroke and TIA is 10–13% at 90 days, with approximately half of events occurring in the first 2 days (20, 21). Multiple scores have been used to predict the early risk of stroke after a TIA or minor stroke, including the ABCD2 score (22, 23) and the ABCD3-I (24) score that include neurovascular and MR imaging (Table 1). Studies have shown imaging-supplemented scores to be superior to clinical scores alone in predicting stroke recurrence in patients with minor stroke or TIA (25, 26). In a meta-analysis of 29 studies and over 130,000 patients, the ABCD2 score lacked reliability in predicting early recurrent stroke risk and in identifying patients with symptomatic large artery atherosclerosis (27), an important prognosticator of early stroke recurrence (25, 28, 29). In fact, a recent multi-center study showed that in patients with minor stroke or TIA, the risk of early stroke recurrence or neurological deterioration was only up to 2% in the absence an infarction on neuroimaging or large artery disease stroke subtype and approximately 30% in those with large artery disease stroke subtype who have an infarction on neuroimaging. In this study, the ABCD2 score was not a predictor of stroke recurrence (30). Another study showed that the addition of perfusion imaging to parenchymal and vascular imaging in patients with minor stroke TIA improved prediction of recurrent cerebrovascular events (31).
Table 1. Clinical stroke risk recurrence scores (23).
Secondary Stroke Prevention
Acute Antiplatelet Agents
Due to the relatively high early risk of recurrent stroke in patients with minor stroke or TIA as compared to those with larger stroke severity, secondary stroke prevention is one of the most important steps in improving outcome in this patient population. Secondary prevention strategies include the use of antiplatelet agents, statins, and aggressive risk factor modification (32). Aggressive therapies targeting platelet inhibition in the absence of indications for anticoagulation is of paramount importance. Aspirin when administered within 48 h of an ischemic stroke has been shown to be effective in reducing the 2-week risk of stroke (2.8–3.3 versus 3.9%) (33, 34). The Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial, which included patients with TIA and minor stroke (NIHSS score ≤3) and excluded patients with isolated sensory symptoms, isolated dizziness, or isolated visual changes found an advantage of short-term dual antiplatelet therapy (aspirin plus clopidogrel) over aspirin monotherapy in the occurrence of secondary stroke (20). An important caveat about the CHANCE trial is that less than half of patients received a lipid-lowering drug and only about one-third received antihypertensive treatment, which is a very different management style in North America. In addition, the event rates, which were close to 10% in both arms far exceed the current rate of secondary stroke in North America – estimated at <5%. The ongoing Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial (POINT) is assessing a similar population in North America with more robust use of statins and antihypertensive agents to see whether the results observed in CHANCE will be replicated. Short-term dual antiplatelet therapy has been used for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic disease (35), symptomatic carotid disease to reduce the number of micro-embolic signals (36), and in those with stuttering lacunar stroke (37, 38) with a potential reduction of stroke risk. While the bleeding risk of long-term dual antiplatelet therapy is higher than that of aspirin alone (39), there is evidence to support the safety of such treatment when used on a short-term basis when the risk of recurrent stroke is highest without an increase in ICH (20). Furthermore, the short-term use of ticagrelor, another antiplatelet agent used for acute coronary syndrome, was compared with aspirin in patients with TIA and minor stroke in the SOCRATES trial (Acute Stroke Or Transient IsChaemic Attack TReated With Aspirin or Ticagrelor and Patient OutcomES). Results of this trial showed no significant difference in recurrent events between the two groups.
In addition to their effect on lowering cholesterol, statins have neuroprotective and anti-inflammatory properties that enhance endothelial function and promote blood flow (40). A small randomized study (41) and a larger retrospective study (42) showed that patients who were continued on a statin acutely after a stroke had a better outcome than those in whom the statin was withdrawn. Therefore, in patients with minor stroke or TIA, early continuation of statin therapy may improve both short-term and long-term stroke prevention strategies.
Evaluation for carotid stenosis is a key step in the diagnostic evaluation of patients with TIA and minor stroke. In patients with this disease, surgical management in addition to best medical therapy is superior to best medical therapy alone, particularly in those with >70% symptomatic stenosis (43). While medical treatment for stroke prevention has improved, carotid endarterectomy or carotid artery stenting still remain an integral part of the treatment for patients with severe symptomatic carotid stenosis. Since the risk of recurrent stroke in such patients is highest in the first 2 weeks after their initial event (44), the AHA/ASA recommends urgent surgery within 2 weeks of symptoms (32).
Atrial Fibrillation Detection
Identifying atrial fibrillation is important in secondary stroke prevention as anticoagulation is superior to antiplatelet agents in reducing the stroke risk of patients with atrial fibrillation. Electrocardiogram and inpatient cardiac telemetry should be part of diagnostic evaluation of patients admitted with ischemic stroke (32). Longer cardiac monitoring via mobile continuous outpatient telemetry (MCOT) or implantable loop records may be indicated in patients with cryptogenic stroke to increase the yield of detecting paroxysmal atrial fibrillation (45). Since the detection rates are higher with MCOT or loop recorders when compared to inpatient telemetry, patients with mild deficits do not need to be admitted solely for inpatient telemetry. Detection rates of paroxysmal atrial fibrillation using various cardiac monitoring are shown in Table 2.
Table 2. Detection rates of paroxysmal atrial fibrillation using various cardiac monitoring strategies (42).
Triaging and Disposition
Any acute, symptomatic stroke-like symptom (transient or not) should be considered a medical emergency. Interventions should be limited at this point to streamline the acquisition of a non-contrast CT scan of the brain to exclude the presence of any intracranial hemorrhage. Patients in whom an acute large vessel occlusion of the anterior or posterior circulation is suspected should be considered for upfront CT angiographic imaging as well. An exception is made for patients who experienced entirely fleeting symptoms and have returned to their neurologic baseline. In these patients, a CT scan can be forgone in lieu of a diffusion-weighted MRI provided hospital resources allow for urgent imaging acquisition (within 24 h) and the patient has no contraindications to MRI. As recommended by the AHA/ASA, all patients with TIA should undergo brain and cervico-cephalic vascular imaging routinely as part of their initial evaluation (7).
A detailed neurological exam that includes, but is not limited, to an NIHSS should be completed in all cases. The provider should remain vigilant of subtle neurological dysfunction, as patients may report symptom resolution, but still exhibit focal abnormalities. This occurred in 26% of patients referred to a same-day TIA clinic when examined by a neurologist in one study (46).
Determining which TIA patients require inpatient hospitalization is largely a factor of institutional resources and the ease of access for patients to receive follow-up care. As such, significant practice variability exists between providers and institutions and this has been a source of frequent debate. On the whole, somewhere between 53 and 91% of all TIA patients presenting to U.S. emergency departments (EDs) are admitted (47–53). The focus should be on determining the underlying etiology of the ischemic event and optimizing individual secondary prevention strategies. Large artery atherosclerosis can be effectively ruled out with brain imaging and vascular imaging of the head and neck (CTA, MRA, or carotid Duplex and transcranial Doppler ultrasound). Cardioembolic etiologies should be explored with electrocardiogram and in-house telemetry, followed by echocardiography and prolonged holter monitoring in selected patients. The suspected etiology of the ischemic event should be classified into the best of the provider’s ability at the time of the initial encounter. ED wait times and limited emergency neurology expertise availability are common drivers for hospitalization. Another determinant of hospitalization is the presence of disabling deficits in gait or swallowing requiring inpatient physical and speech therapy evaluations.
Rapid access TIA clinics and ED observation units provide efficient and cost-effective alternatives to hospitalization for many patients. Observation units, typically located within or near the hospital EDs, provide expedited and protocol-driven care and have a proven track record of safety with TIA (54–57). Outpatient clinics, such as the French SOS-TIA and British EXPRESS models, have successfully implemented 24/7 urgent outpatient follow-up for TIA, while reducing 90-day stroke recurrence by 80% (58–60). As stroke systems of care are increasingly regionalized and hospitals become increasingly incentivized to optimize cost-effective care and decrease inpatient length of stay, these models will likely be increasingly utilized.
Risk stratification tools, such as the ABCD2 score, have been implemented in some systems to triage the urgency of follow-up or determine in whom hospitalization is advised. Current NICE criteria and AHA/ASA guidelines both support this practice, which was found to be safe in a recent Australian study (6, 7, 53, 61). However, as discussed in the preceding section, clinical risk stratification tools are rather imperfect and the more robust-imaging enhanced tools include definitive (and often inpatient) advanced imaging modalities. While clinical risk prediction may be used to augment one’s gestalt of a patient’s short-term recurrent stroke risk, it should not be used as the sole determinant of disposition. Adopting a frontloaded, etiology-focused work-up that optimizes individual secondary prevention strategies is likely to be the best approach, regardless of location (hospital, clinic, or observation unit) (62).
Approximately 30% of patients with minor strokes have poor functional outcomes [defined as modified Rankin scale (mRS) score of 2–6] at 90 days (3, 63). Furthermore, nearly one-third of patients admitted to the hospital for a mild stroke are not discharged home (64, 65) and cannot walk independently at discharge (64). A consistent predictor of outcome in patients with minor deficits is evidence of large vessel occlusion on imaging (17, 18). However, absence of large vessel occlusion is also associated with substantial long-term disability (17, 18). Studies exploring the type of deficits as predictors of outcome in patients with minor stroke yield mixed results. One study showed that the types of deficits do not predict outcome in minor stroke (66). Another study showed that certain items not included in the NIHSS score, such as distal hand weakness and gait disorder, increase the likelihood of a poor functional outcome after a minor stroke (67). Other items of the NIHSS that have been associated with poor outcome in studies include language deficits (67), neglect (68), and leg weakness (68). The NIHSS score and outcome measures assessed in prior studies, such as mRS can underestimate cognitive deficits (69), particularly visuospatial or executive dysfunction (70), and post-stroke fatigue (71) that can occur after a minor stroke. These deficits may cause long-term disability after a mild stroke. Therefore, capturing more sensitive impairment measures that include gait speed, simplified neuropsychological assessments, and examination of distal hand strength and dexterity may aid in making treatment decisions in patients with otherwise mild deficits. Patient-related factors, such as baseline functional status, hobbies, and occupation, may also help treating physicians decide the degree to which the nature of deficits may affect patients’ functional outcome.
A comprehensive approach to the treatment and triaging of patients with minor stroke or TIA may lead to decreased long-term functional deficits in this patient population and still be cost-effective. Randomized trials exploring several treatments and outcome predictors in patients with TIA and minor stroke are underway and aim to advance management and reduce the degree of functional disability.
AY: drafting of manuscript, critical revisions, and final approval. RM: critical revisions and final approval. MJ: critical revisions and final approval. MS: drafting of manuscript, critical revisions, and final approval. BS: critical revisions and final approval. SY: drafting of manuscript, critical revisions, and final approval.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Dr. SY received funding from the New York Stroke Trials Network of Columbia and Cornell (NYCCSTN, NINDS U10NS086728).
1. Dhamoon MS, Moon YP, Paik MC, Boden-Albala B, Rundek T, Sacco RL, et al. Long-term functional recovery after first ischemic stroke: the Northern Manhattan Study. Stroke (2009) 40:2805–11. doi:10.1161/STROKEAHA.109.549576
2. Reeves M, Khoury J, Alwell K, Moomaw C, Flaherty M, Woo D, et al. Distribution of national institutes of health stroke scale in the Cincinnati/Northern Kentucky stroke study. Stroke (2013) 44:3211–3. doi:10.1161/STROKEAHA.113.002881
4. Park TH, Hong KS, Choi JC, Song P, Lee JS, Lee J, et al. Validation of minor stroke definitions for thrombolysis decision making. J Stroke Cerebrovasc Dis (2013) 22:482–90. doi:10.1016/j.jstrokecerebrovasdis.2013.03.006
6. Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, 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. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke (2009) 40:2276–93. doi:10.1161/STROKEAHA.108.192218
7. Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, et al. 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. doi:10.1161/STR.0b013e318284056a
8. Huisa BN, Raman R, Neil W, Ernstrom K, Hemmen TM. Intravenous tissue plasminogen activator for patients with minor ischemic stroke. J Stroke Cerebrovasc Dis (2012) 21:732–6. doi:10.1016/j.jstrokecerebrovasdis.2011.03.009
9. Reid JM, Phillips SJ, Gubitz GJ, Jarrett J, Christian C, Dai D. A case-control study of tissue plasminogen activator for acute ischemic stroke. Can J Neurol Sci (2007) 34:411–6. doi:10.1017/S0317167100007277
10. Greisenegger S, Seyfang L, Kiechl S, Lang W, Ferrari J; Austrian Stroke Unit Registry Collaborators. Thrombolysis in patients with mild stroke: results from the Austrian Stroke Unit Registry. Stroke (2014) 45:765–9. doi:10.1161/STROKEAHA.113.003827
11. Strbian D, Piironen K, Meretoja A, Sairanen T, Putaala J, Tiainen M, et al. Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms. Int J Stroke (2013) 8:293–9. doi:10.1111/j.1747-4949.2012.00808.x
13. IST-3 Collaborative Group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet (2012) 379:2352–63. doi:10.1016/S0140-6736(12)60768-5
14. ClinicalTrials.gov: A service of the U.S. National Institutes of Health [Internet]. A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS). NCT02072226. Washington, DC: National Institutes of Health (2016). [cited 2016 June 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02072226
15. ClinicalTrials.gov: A service of the U.S. National Institutes of Health [Internet]. TNK-tPA Evaluation for Minor Ischemic Stroke with Proven Occlusion (TEMPO-1). NCT01654445. Washington, DC: National Institutes of Health (2014). [cited 2016 June 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT01654445
16. Campbell BC, Hill MD, Rubiera M, Menon BK, Demchuk A, Donnan GA, et al. Safety and efficacy of solitaire stent thrombectomy: individual patient data meta-analysis of randomized trials. Stroke (2016) 47:798–806. doi:10.1161/STROKEAHA.115.012360
17. Nedeltchev K, Schwegler B, Haefeli T, Brekenfeld C, Gralla J, Fischer U, et al. Outcome of stroke with mild or rapidly improving symptoms. Stroke (2007) 38:2531–5. doi:10.1161/STROKEAHA.107.482554
18. Rajajee V, Kidwell C, Starkman S, Ovbiagele B, Alger JR, Villablanca P, et al. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke. Neurology (2006) 67:980–4. doi:10.1212/01.wnl.0000237520.88777.71
19. Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke (2015) 46:3020–35. doi:10.1161/STR.0000000000000074
21. Daubail B, Durier J, Jacquin A, Hervieu-Bègue M, Khoumri C, Osseby GV, et al. Factors associated with early recurrence at the first evaluation of patients with transient ischemic attack. J Clin Neurosci (2014) 21:1940–4. doi:10.1016/j.jocn.2014.03.035
22. Josephson SA, Sidney S, Pham TN, Bernstein AL, Johnston SC. Higher ABCD2 score predicts patients most likely to have true transient ischemic attack. Stroke (2008) 39:3096–8. doi:10.1161/STROKEAHA.108.514562
23. Ghandehari K, Ahmadi F, Ebrahimzadeh S, Shariatinezhad K, Ghandehari K. The ABCD(2) score is highly predictive of stroke in minor ischemic stroke patients. Transl Stroke Res (2012) 3:273–8. doi:10.1007/s12975-012-0146-0
24. Purroy F, Jiménez-Caballero PE, Mauri-Capdevila G, Torres MJ, Gorospe A, Ramírez Moreno JM, et al. Predictive value of brain and vascular imaging including intracranial vessels in transient ischaemic attack patients: external validation of the ABCD3-I score. Eur J Neurol (2013) 20:1088–93. doi:10.1111/ene.12141
25. 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) 45:418–25. doi:10.1161/STROKEAHA.113.003077
26. Arsava EM, Kim GM, Oliveira-Filho J, Gungor L, Noh HJ, Lordelo Mde J, et al. Prediction of early recurrence after acute ischemic stroke. JAMA Neurol (2016) 73(4):396–401. doi:10.1001/jamaneurol.2015.4949
27. Wardlaw JM, Brazzelli M, Chappell FM, Miranda H, Shuler K, Sandercock PA, et al. ABCD2 score and secondary stroke prevention: meta-analysis and effect per 1,000 patients triaged. Neurology (2015) 85:373–80. doi:10.1212/WNL.0000000000001780
28. Purroy F, Jiménez Caballero PE, Gorospe A, Torres MJ, Alvarez-Sabin J, Santamarina E, et al. Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores. Cerebrovasc Dis (2012) 33:182–9. doi:10.1159/000334771
29. Purroy F, Montaner J, Molina CA, Delgado P, Ribo M, Alvarez-Sabin J. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke (2007) 38:3225–9. doi:10.1161/STROKEAHA.107.488833
30. Yaghi S, Rostanski SK, Boehme AK, Martin-Schild S, Samai A, Silver B, et al. Imaging parameters and recurrent cerebrovascular events in patients with minor stroke or transient ischemic attack. JAMA Neurol (2016) 73(5):572–8. doi:10.1001/jamaneurol.2015.4906
31. Asdaghi N, Hill MD, Coulter JI, Butcher KS, Modi J, Qazi A, et al. Perfusion MR predicts outcome in high-risk transient ischemic attack/minor stroke: a derivation-validation study. Stroke (2013) 44:2486–92. doi:10.1161/STROKEAHA.111.000208
32. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. 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) 45:2160–236. doi:10.1161/STR.0000000000000024
33. International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet (1997) 349:1569–81. doi:10.1016/S0140-6736(97)04011-7
34. CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet (1997) 349:1641–9. doi:10.1016/S0140-6736(97)04010-5
35. Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med (2011) 365:993–1003. doi:10.1056/NEJMoa1105335
36. Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler M, et al. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation (2005) 111:2233–40. doi:10.1161/01.CIR.0000163561.90680.1C
37. Kawano H, Nakajima M, Inatomi Y, Yonehara T, Ando Y. Loading dose of clopidogrel in combination with other antithrombotic therapy for capsular warning syndrome. J Stroke Cerebrovasc Dis (2014) 23:1265–6. doi:10.1016/j.jstrokecerebrovasdis.2013.09.020
38. Meyer DM, Albright KC, Allison TA, Grotta JC. LOAD: a pilot study of the safety of loading of aspirin and clopidogrel in acute ischemic stroke and transient ischemic attack. J Stroke Cerebrovasc Dis (2008) 17:26–9. doi:10.1016/j.jstrokecerebrovasdis.2007.09.006
39. SPS3 Investigators, Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med (2012) 367:817–25. doi:10.1056/NEJMoa1204133
41. Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology (2007) 69:904–10. doi:10.1212/01.wnl.0000269789.09277.47
42. Flint AC, Kamel H, Navi BB, Rao VA, Faigeles BS, Conell C, et al. Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival. Stroke (2012) 43:147–54. doi:10.1161/STROKEAHA.111.627729
46. Moreau F, Jeerakathil T, Coutts SB; FRCPC for the ASPIRE investigators. Patients referred for TIA may still have persisting neurological deficits. Can J Neurol Sci (2012) 39:170–3. doi:10.1017/S0317167100013172
47. Chaudhry SA, Tariq N, Majidi S, Afzal MR, Hassan AE, Watanabe M, et al. Rates and factors associated with admission in patients presenting to the ED with TIA in the United States-2006 to 2008. Am J Emerg Med (2013) 31:516–9. doi:10.1016/j.ajem.2012.10.003
48. Coben JH, Owens PL, Steiner CA, Crocco TJ. Hospital and demographic influences on the disposition of transient ischemic attack. Acad Emerg Med (2008) 15:171–6. doi:10.1111/j.1553-2712.2008.00041.x
49. Perry JJ, Goindi R, Brehaut J, Taljaard M, Schneider S, Stiell IG. Emergency physicians’ management of transient ischemic attack and desired sensitivity of a clinical decision rule for stroke in three countries. CJEM (2011) 13:19–27.
50. Talwalkar A, Uddin S. Trends in Emergency Department Visits for Ischemic Stroke and Transient Ischemic Attack: United States, 2001–2011. Hyattsville, MD: National Center for Health Statistics (2015). NCHS Data Brief No 194.
52. Ben-Yakov M, Kapral MK, Fang J, Li S, Vermeulen MJ, Schull MJ. The association between emergency department crowding and the disposition of patients with transient ischemic attack or minor stroke. Acad Emerg Med (2015) 22:1145–54. doi:10.1111/acem.12766
53. Griffiths D, Sturm J, Heard R, Reyneke E, Whyte S, Clarke T, et al. Can lower risk patients presenting with transient ischaemic attack be safely managed as outpatients? J Clin Neurosci (2014) 21:47–50. doi:10.1016/j.jocn.2013.02.028
54. Stead LG, Bellolio MF, Suravaram S, Brown RD Jr, Bhagra A, Gilmore RM, et al. Evaluation of transient ischemic attack in an emergency department observation unit. Neurocrit Care (2009) 10:204–8. doi:10.1007/s12028-008-9146-z
55. Ross MA, Compton S, Medado P, Fitzgerald M, Kilanowski P, O’Neil BJ. An emergency department diagnostic protocol for patients with transient ischemic attack: a randomized controlled trial. Ann Emerg Med (2007) 50:109–19. doi:10.1016/j.annemergmed.2007.03.008
56. Nahab F, Leach G, Kingston C, Mir O, Abramson J, Hilton S, et al. Impact of an emergency department observation unit transient ischemic attack protocol on length of stay and cost. J Stroke Cerebrovasc Dis (2012) 21:673–8. doi:10.1016/j.jstrokecerebrovasdis.2011.02.017
57. Torres Macho J, Peña Lillo G, Pérez Martínez D, González Mansilla A, Gámez Díez S, Mateo Alvarez S, et al. Outcomes of atherothrombotic transient ischemic attack and minor stroke in an emergency department: results of an outpatient management program. Ann Emerg Med (2011) 57:510–6. doi:10.1016/j.annemergmed.2010.09.009
58. Lavallée PC, Cabrejo L, Labreuche J, Mazighi M, Meseguer E, Guidoux C, et al. Spectrum of transient visual symptoms in a transient ischemic attack cohort. Stroke (2013) 44:3312–7. doi:10.1161/STROKEAHA.113.002420
59. Luengo-Fernandez R, Gray AM, Rothwell PM. Effect of urgent treatment for transient ischaemic attack and minor stroke on disability and hospital costs (EXPRESS study): a prospective population-based sequential comparison. Lancet Neurol (2009) 8:235–43. doi:10.1016/S1474-4422(09)70019-5
60. Rothwell PM, Giles MF, Chandratheva A, Marquardt L, Geraghty O, Redgrave JN, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet (2007) 370:1432–42. doi:10.1016/S0140-6736(07)61448-2
61. National Institute for Health and Clinical Excellence. Stroke and Transient Ischaemic Attack in Over 16s: Diagnosis and Initial Management, 23 July 2008 [cited 1 June 2016] (2008). Available from: https://www.nice.org.uk/guidance/Cg68
63. Khatri P, Conaway MR, Johnston KC; Acute Stroke Accurate Prediction Study (ASAP) Investigators. Ninety-day outcome rates of a prospective cohort of consecutive patients with mild ischemic stroke. Stroke (2012) 43:560–2. doi:10.1161/STROKEAHA.110.593897
64. Smith EE, Fonarow GC, Reeves MJ, Cox M, Olsen DM, Hernandez AF, et al. Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With The Guidelines-Stroke. Stroke (2011) 42:3110–5. doi:10.1161/STROKEAHA.111.613208
65. Willey JZ, Stillman J, Rivolta JA, Vieira J, Doyle MM, Linares G, et al. Too good to treat? Outcomes in patients not receiving thrombolysis due to mild deficits or rapidly improving symptoms. Int J Stroke (2012) 7(3):202–6. doi:10.1111/j.1747-4949.2011.00696.x
66. Leira EC, Ludwig BR, Gurol ME, Torner JC, Adams HP Jr. The types of neurological deficits might not justify withholding treatment in patients with low total National Institutes of Health Stroke Scale scores. Stroke (2012) 43:782–6. doi:10.1161/STROKEAHA.111.620674
67. Wendt M, Tutuncu S, Fiebach JB, Scheitz JF, Audebert HJ, Nolte CH. Preclusion of ischemic stroke patients from intravenous tissue plasminogen activator treatment for mild symptoms should not be based on low National Institutes of Health Stroke Scale Scores. J Stroke Cerebrovasc Dis (2013) 22:550–3. doi:10.1016/j.jstrokecerebrovasdis.2013.01.021
68. Sato S, Uehara T, Ohara T, Suzuki R, Toyoda K, Minematsu K, et al. Factors associated with unfavorable outcome in minor ischemic stroke. Neurology (2014) 83:174–81. doi:10.1212/WNL.0000000000000572
69. Bocti C, Legault V, Leblanc N, Berger L, Nasreddine Z, Beaulieu-Boire I, et al. Vascular cognitive impairment: most useful subtests of the Montreal Cognitive Assessment in minor stroke and transient ischemic attack. Dement Geriatr Cogn Disord (2013) 36:154–62. doi:10.1159/000351674
Keywords: minor stroke, transient ischemic attack, minor stroke outcome, treatment, recurrent stroke risk, stroke prevention
Citation: Yakhkind A, McTaggart RA, Jayaraman MV, Siket MS, Silver B and Yaghi S (2016) Minor Stroke and Transient Ischemic Attack: Research and Practice. Front. Neurol. 7:86. doi: 10.3389/fneur.2016.00086
Received: 17 March 2016; Accepted: 23 May 2016;
Published: 10 June 2016
Edited by:Thanh G. Phan, Monash Health, Australia
Reviewed by:Alexander Tsiskaridze, Tbilisi State University, Georgia
Richard Zweifler, Ochsner Health System, USA
Copyright: © 2016 Yakhkind, McTaggart, Jayaraman, Siket, Silver and Yaghi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Brian Silver, email@example.com