Definition and Evaluation of Transient Ischemic Attack
Gerald Hurowitz, M.D.·Published 14 October 2009·15 min read
Key points
This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient ischemic attacks.
TIAs are brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction.
Large cohort and population-based studies reported in the last 5 years have demonstrated a higher risk of early stroke after TIA than generally suspected.
Accordingly, clinicians are in need of updated guidance regarding the definition, urgency, and evaluation of patients with TIA.
This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient ischemic attacks. Formal evidence review included a structured literature search of Medline from 1990 to June 2007 and data synthesis employing evidence tables, meta-analyses, and pooled analysis of individual patient-level data.
The review supported endorsement of the following, tissue-based definition of transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Patients with TIAs are at high risk of early stroke, and their risk may be stratified by clinical scale, vessel imaging, and diffusion magnetic resonance imaging.
Diagnostic recommendations include: TIA patients should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences; noninvasive imaging of the cervical vessels should be performed and noninvasive imaging of intracranial vessels is reasonable; electrocardiography should occur as soon as possible after TIA and prolonged cardiac monitoring and echocardiography are reasonable in patients in whom the vascular etiology is not yet identified; routine blood tests are reasonable; and it is reasonable to hospitalize patients with TIA if they present within 72 hours and have an ABCD2 score >3, indicating high risk of early recurrence, or the evaluation cannot be rapidly completed on an outpatient basis.
Recent scientific studies have revised our understanding of 3 key aspects of transient ischemic attack (TIA): how it is best defined, what the early risk of stroke and other vascular outcomes is, and how it is best evaluated. This statement reviews and synthesizes recent scientific advances regarding the definition, urgency, and evaluation of TIA and is designed to aid the clinician in the short- and long-term management of patients with TIA.
Definition
TIAs are brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction. In the past, TIAs were operationally defined as any focal cerebral ischemic event with symptoms lasting < 24 hours. Recently, however, studies from many groups worldwide have demonstrated that this arbitrary time threshold was too broad because 30% to 50% of classically defined TIAs show brain injury on diffusion-weighted magnetic resonance (MR) imaging (MRI).
Several groups have advanced newer, neuroimaging-informed, operational definitions of TIA such as "a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction" (p 1715). However, with rare exceptions, the newer definitions have not yet been formally considered for endorsement or rejection by authoritative organizations. This statement reviews the data supporting revision of the definition of TIA. For those aspects found to be strong or conclusive, this statement endorses a specific revised definition, moving the field forward.
Written and revised by
Gerald Hurowitz, M.D.
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Large cohort and population-based studies reported in the last 5 years have demonstrated a higher risk of early stroke after TIA than generally suspected. Ten percent to 15% of patients have a stroke within 3 months, with half occurring within 48 hours. Acute treatments for TIA also have evolved, with new data supporting early rather than delayed carotid endarterectomy for TIA patients with carotid stenosis.
Methods for Patient Evaluation
Over the last decade, substantial new diagnostic advances have occurred, including the widespread availability of MR angiography (MRA) and computed tomographic (CT) angiography (CTA), the recognition that diffusion MR frequently shows abnormalities in classic TIA patients, and the development and validation of risk stratification algorithms that identify TIA patients at higher and lower risk of early stroke.
Accordingly, clinicians are in need of updated guidance regarding the definition, urgency, and evaluation of patients with TIA. Formal levels of evidence and classes of recommendations are used. Because there are few definitive clinical trials in this area, this document is a scientific statement rather than a guideline. The treatment of TIA was not addressed by this writing panel because it is already covered in the Stroke Council’s guideline statements on treatment of acute cerebral ischemia and secondary prevention after ischemic stroke and TIA.
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Review Methods and Key Words
This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient neurological symptoms resulting from brain, retinal, and spinal cord ischemia. A formal literature search was performed of the following Medline database: using the search strategy transient ischemic attack crossed with terms definition, epidemiology, incidence, prevalence, prognosis, recurrent stroke, diagnosis, imaging, magnetic resonance, diffusion, computed tomography, ultrasound, ECG, Holter, echocardiogram, and laboratory tests, covering the dates 1990 through June 2007. Writing panel members were each assigned topic areas and filtered the retrieved articles using the criteria identified in the Stroke Council’s Manual for Guidelines and Scientific Statements to identify high- or medium-quality studies of diagnostic tests and prognostic instruments. Data were synthesized through the use of evidence tables, meta-analyses, and pooled analysis of individual patient-level data. The American Heart Association (AHA)/American College of Cardiology/Stroke Council Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed anonymously by 3 expert peer reviewers, by the members of the Stroke Council’s Scientific Statements Oversight Committee, and by the members of the Stroke Council Leadership Committee.
TIA Epidemiology
Precise estimates of the incidence and prevalence of TIAs are difficult to determine mainly because of the varying criteria used in epidemiological studies to identify TIA. Lack of recognition by both the public and healthcare systems of the transitory focal neurological symptoms associated with TIAs also may lead to gross underestimates. Given these limitations, the incidence of TIA in the United States has been estimated to be {approx}200 000 to 500 000 per year, with a population prevalence of 2.3% that translates into {approx}5 million individuals.
TIA incidence rates have been projected from different study cohorts in the United States and abroad, ranging from 0.37 to 1.1 per 1000 per year. An overall TIA incidence rate of 1.1 per 1000 US population has been estimated on the basis of a review of the National Hospital Ambulatory Medical Care Survey among 2 623 000 TIA cases diagnosed in US emergency departments between 1992 and 2000. From the Greater Cincinnati/Northern Kentucky population between 1993 and 1994, the overall race-, age-, and gender-adjusted incidence rate for TIA was found to be 0.83 per 1000. Between the years 2002 and 2004, the Oxford Vascular Study determined that the overall incidence rate of TIA was 0.66 per 1000 per year.
Meanwhile, in rural and urban areas of Portugal, the crude overall annual incidence of TIA per 1000 population was found to be 0.67 and slightly higher in the rural region at 0.96 than in the urban area at 0.61. Comparable to stroke incidence, TIA incidence markedly increases with age and varies by race-ethnicity. Increased likelihood of TIA with advancing age was supported in recent UK studies, with 6.41 per 1000 for patients > 85 years of age. In the Greater Cincinnati/Northern Kentucky population, the greatest incidence of TIA occurred in black men ?85 of age at 16 events per 1000. The incidence of TIA increases exponentially with age regardless of race and gender. In addition, TIAs were found to be more common in Mexican Americans compared with non-Hispanic whites at younger ages (45 to 59 years) but not at older ages.
TIA prevalence rates vary, depending on the age distribution of the study population. For instance, the Cardiovascular Health Study estimated a prevalence of TIA in men of 2.7% for 65 to 69 years of age and 3.6% for 75 to 79 years of age. For women, TIA prevalence was 1.6% for 65 to 69 years of age and 4.1% for 75 to 79 years of age. In the younger Atherosclerosis Risk in Communities cohort, the overall prevalence of TIAs was found to be 0.4% among adults 45 to 64 years of age.
Among patients who present with stroke, the prevalence of prior TIA has been reported to range from 7% to 40%. The percentage varies, depending on such factors as how TIA is defined, which stroke subtypes are evaluated, and whether the study is a population-based series or a hospital-based series. In the population-based Northern Manhattan Stroke Study, the prevalence of TIAs among those who presented with first ischemic stroke was 8.7%. The majority of TIAs occurred within 30 days of the patient’s first ischemic stroke, with 41% of the TIAs lasting <1 hour.
Studies that have included patients with prior stroke such as the Harvard Stroke Registry and National Institute of Neurological Disorders and Stroke data bank have reported higher rates of TIAs as great as 50% among those with atherothrombotic stroke. In 2 population-based studies (Oxford Vascular Study and Oxfordshire Community Stroke Project) and 2 other randomized trials (UK TIA Aspirin Trial and the European Carotid Surgery Trial), the timing of a TIA before stroke was highly consistent, with 17% occurring on the day of the stroke, 9% on the previous day, and another 43% at some point during the 7 days before the stroke. In another population-based study that was biethnic with Mexican Americans and non-Hispanic whites, approximately half of the 90-day stroke risk for TIA occurred within the first 2 days, suggesting that in general TIA patients are at very high risk for a recurrent cerebrovascular event (see TIA: Short-Term Stroke Risk below).
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Variability in the use of brain imaging and the type of diagnostic imaging used can also markedly affect estimates of the incidence and prevalence of TIAs. One study has estimated that a revision of TIA definitions to include the absence of changes on an MRI could lead to a reduction in the incidence of TIAs by {approx}30% and a resultant 7% increase in the number of cases labeled as stroke. Thus, a blend of factors related to the diagnostic process influences the ultimate diagnosis of a TIA.
Definition
Often, health professionals and the public consider TIAs benign but regard strokes as serious. These views are incorrect. Stroke and TIA are on a spectrum of serious conditions involving brain ischemia. Both are markers of reduced cerebral blood flow and an increased risk of disability and death. However, TIAs offer an opportunity to initiate treatment that can forestall the onset of permanently disabling injury.23,24
The traditional definition of a TIA was a sudden, focal neurological deficit of presumed vascular origin lasting <24 hours. The arbitrary 24-hour threshold used to distinguish TIA from stroke arose in the mid-1960s. At that time, it was assumed that transient symptoms disappeared completely because no permanent brain injury had occurred. The term TIA was applied to events lasting up to 24 hours, and the term reversible ischemic neurological deficit was applied to events lasting 24 hours to 7 days. Only symptoms enduring >7 days were thought to reliably indicate infarction and received the designation stroke. During the 1970s, it became clear that the great preponderance of events lasting 24 hours to 7 days were associated with infarction, rendering the term reversible ischemic neurological deficit obsolete, and it disappeared from standard nomenclature.
More recently, high-resolution CT and especially diffusion-weighted MRI studies have demonstrated that many ischemic episodes with symptoms lasting < 24 hours also are associated with new infarction. One third of individuals with traditionally defined TIAs exhibit the signature of new infarction on diffusion-weighted MRI. These findings highlight an inconsistency between the concept of TIA (ischemia causing symptoms but no infarction) and the traditional definition of TIA. With these observations in mind, a group of cerebrovascular physicians proposed a tissue-based, rather than time-based, definition in 2002: "transient ischemic attack (TIA): a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction" (p 1715).
This proposed new definition has been well received. Many cerebrovascular experts endorsed the new definition, and it has been widely incorporated into the study design of major clinical trials (Warfarin-Aspirin Recurrent Stroke Study [WARSS], Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment [RESPECT], Prevention Regimen for Effectively Avoiding Second Strokes [PROFESS], Evaluation of the STARflex Septal Closure System in Patients With a Stroke or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a PFO [CLOSURE 1]). However, some have raised concerns. To shed additional light on key issues, individual committee members organized a pooled, patient-level data analysis integrating data from published studies of TIA and MRI.
TIA: Short-Term Stroke Risk
It has long been recognized that TIA can portend stroke, with several studies demonstrating elevated long-term stroke risk. Numerous studies also have shown that the short-term risk of stroke is particularly high, with most studies finding risks exceeding 10% in 90 days. Risk is particularly high in the first few days after TIA, with most studies finding that one quarter to one half of the strokes that occur within 3 months occur within the first 2 days. For example, studies in northern California and Oxfordshire found the risk of stroke in the first 24 hours after TIA to be {approx}4%, which is about twice the risk of myocardial infarction or death in patients presenting with acute coronary syndromes ({approx}2% at 24 hours).87 These findings underscore the need for prompt evaluation and treatment of patients with symptoms of ischemia.
Ischemic stroke appears to carry a lower short-term risk of subsequent ischemic stroke than TIA, with reported 3-month risks generally ranging from 4% to 8%. The degree of early recovery may be predictive of greater risk, possibly by indicating that tissue is still at risk.
Risk of cardiac events also is elevated after TIA. In 1 large study, 2.6% of TIA patients were hospitalized for major cardiovascular events (myocardial infarction, unstable angina, or ventricular arrhythmia) within 90 days. Over the course of ≥5 years, a nearly equal number of patients with TIA will have myocardial infarction or sudden cardiac death as will have a cerebral infarction. A prior AHA scientific statement provides detailed guidance on the coronary risk evaluation in patients with TIA.
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Risk Stratification
Several studies have identified risk factors for stroke after TIA, which may be useful in making initial management decisions. Three very similar formal prediction rules have been developed and cross-validated in northern California and Oxfordshire. The California score and the ABCD score both predict short-term risk of stroke well in independent populations of patients presenting acutely after a TIA. The newer ABCD2 score was derived to provide a more robust prediction standard and incorporates elements from both prior scores. Patients with TIA score points (indicated in parentheses) for each of the following factors: age ≥60 years (1); blood pressure ≥140/90 mm Hg on first evaluation (1); clinical symptoms of focal weakness with the spell (2) or speech impairment without weakness (1); duration ≥60 minutes (2) or 10 to 59 minutes (1); and diabetes (1). In combined validation cohorts, the 2-day risk of stroke was 0% for scores of 0 or 1, 1.3% for 2 or 3, 4.1% for 4 or 5, and 8.1% for 6 or 7.
These prediction rules do not incorporate imaging findings, which have been shown to have prognostic value. The presence of a new infarct on brain imaging, which was consistent with the classic definition of TIA but would now lead to a diagnosis of stroke, is associated with an {approx}2- to 15-fold increase in subsequent short-term risk of stroke. Evidence of vessel occlusion on acute brain MRA also has been associated with a 4-fold increased short-term risk of stroke. MRI changes have been associated with the clinical factors identified in prior prediction rules, so it is unclear how much they will add to validated prediction rules such as ABCD.
Hospitalization
Hospitalization rates after TIA vary widely among practitioners, hospitals, and regions. A study from the National Hospital Ambulatory Medical Care Survey found that 54% of patients with TIA were admitted to the hospital, with rates varying from 68% in the northwest United States to 41% in the west.
Close observation during hospitalization has the potential to allow more rapid and frequent administration of tissue plasminogen activator should a stroke occur. A cost-utility analysis demonstrated that hospitalization was cost-effective for patients with 24-hour risk of stroke >4% solely on this basis. Prospective studies are required on the efficacy and safety of the use of tissue plasminogen activator in patients with recent prior clinical symptoms lasting < 24 hours associated with small DWI lesions. In the past, these patients were diagnosed as having TIA, which did not contraindicate lytic therapy. Now, these patients will be classified as minor cerebral infarction patients. However, it is likely that the risk of bleeding with lytic therapy is much lower in these patients than in patients with large recent prior cerebral infarcts. Hospitalization may have other benefits as well. It permits cardiac monitoring and facilitates rapid diagnostic evaluation. Rates of adherence to secondary prevention interventions may also be greater after hospitalization. No randomized trial has evaluated the benefit of hospitalization or the utility of the ABCD2 score in assisting with triage decisions.
References
1. Albers GW, Caplan LR, Easton JD, Fayad PB, Mohr JP, Saver JL, Sherman DG, for the TIA Working Group. Transient ischemic attack: proposal for a new definition. N Engl J Med. 2002; 347: 1713–1716.
2. Albucher JF, Martel P, Mas JL. Clinical practice guidelines: diagnosis and immediate management of transient ischemic attacks in adults. Cerebrovasc Dis. 2005; 20: 220–225.
3. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007; 38: 1655–1711.
5. Johnston SC, Fayad PB, Gorelick PB, Hanley DF, Shwayder P, van Husen D, Weiskopf T. Prevalence and knowledge of transient ischemic attack among US adults. Neurology. 2003; 60: 1429–1434.
6. Edlow JA, Kim S, Pelletier AJ, Camargo CA Jr. National study on emergency department visits for transient ischemic attack, 1992–2001. Acad Emerg Med. 2006; 13: 666–672.
7. Kleindorfer D, Panagos P, Pancioli A, Khoury J, Kissela B, Woo D, Schneider A, Alwell K, Jauch E, Miller R, Moomaw C, Shukla R, Broderick JP. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke. 2005; 36: 720–723.
8. Correia M, Silva MR, Magalhaes R, Guimaraes L, Silva MC. Transient ischemic attacks in rural and urban northern Portugal: incidence and short-term prognosis. Stroke. 2006; 37: 50–55.
9. Rothwell PM, Coull AJ, Giles MF, Howard SC, Silver LE, Bull LM, Gutnikov SA, Edwards P, Mant D, Sackley CM, Farmer A, Sandercock PA, Dennis MS, Warlow CP, Bamford JM, Anslow P, for the Oxford Vascular Study. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet. 2004; 363: 1925–1933.
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.
J. Donald Easton, MD, FAHA, Chair; Jeffrey L. Saver, MD, FAHA, Vice-Chair; Gregory W. Albers, MD; Mark J. Alberts, MD, FAHA; Seemant Chaturvedi, MD, FAHA, FAAN; Edward Feldmann, MD, FAHA; Thomas S. Hatsukami, MD; Randall T. Higashida, MD, FAHA; S. Claiborne Johnston, MD, PhD; Chelsea S. Kidwell, MD, FAHA; Helmi L. Lutsep, MD; Elaine Miller, DNS, RN, CRRN, FAHA Ralph L. Sacco, MD, MS, FAAN, FAHA
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