COMMENTARY

Toward an emergency response to transient ischemic attacks

David J. Gladstone, MD, FRCPC

VOL 117 / NO 1 / JANUARY 2005 / POSTGRADUATE MEDICINE

The author discloses no financial interests in this article and no unlabeled uses of any product mentioned.

Gladstone DJ. Toward an emergency response to transient ischemic attacks. Postgrad Med 2005;117(1):9-14

Optimizing stroke prevention is an urgent priority. In the United States, someone experiences a stroke every 45 seconds, and someone dies of a stroke every 3 minutes (1). About 15% to 20% of strokes are preceded by a transient ischemic attack (TIA); few other medical conditions come with such a warning.

Early recognition of TIAs affords a special opportunity for preventative intervention. Primary care physicians play an integral role in the identification, investigation, and treatment of these high-risk patients.

Small strokes, big risks

Many recent studies (2-8) confirm that patients who experience a TIA have a high risk of early recurrent stroke or other vascular events. The risk of stroke in the 90 days after a TIA is between 10% and 20% (2-8). It is important to note that this risk is front-loaded--half the strokes that occur within 90 days happen in the first 48 hours after a TIA (2,3) (figure 1). Patients and their family members should be informed of this danger. Clinical risk factors associated with early stroke are age greater than 60 years, diabetes, TIA duration of more than 10 minutes, and TIA symptoms involving either weakness or speech impairment (2). A study by Johnston and colleagues (2) showed that patients who exhibited all five of these characteristics had a 1 in 3 risk of stroke within 90 days. Similarly, findings from the Ontario Stroke Registry (3) suggested a 30-day risk of stroke or death of 8% after a first TIA; this risk increased to 9% for TIAs accompanied by a speech or language deficit and to 12% for TIAs that caused a motor deficit.

Patients with carotid artery disease are at especially high risk of early recurrent events after a TIA. According to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) database (8), patients with a hemispheric TIA and ipsilateral carotid artery disease (50% to 99% stenosis) have a 90-day stroke risk of 1 in 5 (independent of the degree of stenosis).

Patients with TIA are also at risk for early and late myocardial infarction and cardiac death. For some patients, it is appropriate to consider noninvasive testing for occult coronary artery disease (2,9).

Knowledge-practice gaps

Unfortunately, large gaps exist between what we know about preventing stroke in high-risk patients and what is actually performed in routine clinical practice. Effective treatment strategies to reduce stroke risk exist but are often underutilized. These include antiplatelet therapies, use of warfarin (Coumadin) for atrial fibrillation, carotid endarterectomy for appropriate surgical candidates, and blood pressure control for hypertensive patients.

According to a 2003 US survey (10), only 8% of the 10,000 participants knew the definition of TIA and only 9% could identify a typical symptom. Of those respondents who had experienced a TIA, more than one third reported that they did not seek medical attention within 24 hours of symptom onset (10). Surprisingly, in a US survey of 200 primary care physicians (11), only 22% were able to correctly identify the typical symptoms and duration of a TIA. We need to raise public awareness that TIAs are as much of a medical emergency as acute stroke or acute coronary syndromes, and we need to change physician attitudes that have traditionally underestimated the serious nature of TIAs and the need for prompt action.

It is surprising that for a condition as serious and as common as TIA (the prevalence among US adults over age 65 is 1 in 15 (10)), there has been little consensus on the best approach to acute management of these patients. Published guidelines are outdated and need revisions to reflect our current understanding of the natural history of TIA.

Tremendous geographic variations exist in current practice, and outpatient and emergency management is often suboptimal (3,12,13). For example, in some medical centers, patients are unlikely to undergo neuroimaging or carotid ultrasound studies within 30 days of a TIA, even if they present to an emergency department (3). All hospitals should reassess their local protocols for managing patients with TIA and regularly monitor performance with practice audits.

Diagnostic challenges

Accurate diagnosis of a TIA can be difficult. Not all transient neurologic symptoms represent TIAs, and overdiagnosis of TIA is common in primary care settings and emergency departments. Although the traditional definition of TIA is a spell of focal neurologic symptoms lasting up to 24 hours, in reality most attacks last closer to 24 minutes. Some authorities have called for a revised definition in which the duration of symptoms is 1 hour or less (14).

Conditions commonly mistaken for a TIA include migraine aura (especially without an accompanying headache, ie, acephalgic migraine), focal seizure, presyncope or syncope, vertigo (eg, benign paroxysmal positional vertigo or other peripheral vestibulopathy), transient global amnesia, anxiety, confusion, falls, and peripheral nerve palsies (eg, Bell's palsy). Frontline physicians need to be familiar with this differential diagnosis; careful history taking from the patient and witnesses can often help distinguish a true TIA from its "mimics."

Nonspecific or nonfocal neurologic symptoms (eg, light-headedness, generalized weakness, dizziness) and symptoms lasting only a few seconds are unlikely to indicate a TIA. Transient, isolated symptoms of vertigo, dysarthria, or diplopia are also less likely to represent a TIA, although exceptions exist.

Because the implications of a TIA diagnosis are significant, such a diagnostic label should be reserved for patients in whom there is a high degree of certainty that the event was a result of focal brain ischemia. To enhance communication and help direct triage decisions, physicians should consider adding qualifying descriptors such as definite, probable, or possible/uncertain along with time variables such as acute (within 48 hours), recent, or remote.

Stratification into high-risk or low-risk categories based on clinical features and neuroimaging findings should be attempted (table 1). Similar to the approach to giant cell arteritis (in which a suspected diagnosis commits the physician to initiating treatment and arranging a biopsy), a diagnosis of TIA obligates the treating physician to ensure that urgent diagnostic investigations are undertaken and preventive treatment is initiated (see article by Dr Weir and colleagues in this symposium).

Table 1. Some factors that may indicate a higher stroke risk after a TIA*

Risk factor profile** TIA accompanied by motor deficit (eg, hemiparesis) TIA accompanied by speech or language deficit (eg, aphasia) TIA duration >10 min Age >60 yr Diabetes Abnormal neuroimaging results (eg, CT scan shows infarction or diffusion-weighted MRI shows acute cerebral ischemic lesions) Known or suspected carotid artery disease (eg, carotid bruit, evidence of generalized large-artery atherosclerotic occlusive disease) Suspected carotid or vertebral artery dissection (eg, TIA associated with or preceded by head, neck, or facial pain, especially if posttraumatic or in young patient who has no traditional vascular risk factors; presence of Horner's syndrome, ie, ptosis and small pupil) Atrial fibrillation or other high-risk cardiac source of brain embolism (eg, known or suspected akinetic left ventricle, endocarditis) First TIA (ie, no history of TIA or stroke) Acute TIA (ie, patient presents within 24 hr of symptom onset) Crescendo TIA CT, computed tomographic; MRI, magnetic resonance imaging; TIA, transient ischemic attack. *Evidence-based data are limited, and specific guidelines are lacking or outdated. **As described by Johnston et al (2).

Emergency evaluation

We need to become as aggressive in our approach to TIAs as we are toward acute coronary syndromes. Because stroke symptoms can result from many different causes, diagnostic investigations for the mechanism of ischemia in each patient are necessary and are a prerequisite for selecting the most appropriate preventive treatment (15). According to some guidelines, the initial diagnostic evaluation should be completed within 1 week (16), although some patients should be investigated more quickly (17) (see table 1).

A main goal of diagnostic evaluation is to identify patients with symptomatic carotid artery disease who will benefit from carotid endarterectomy. Noninvasive vascular imaging of the carotid arteries (with Doppler ultrasonography, magnetic resonance angiography, or computed tomographic [CT] angiography (18)) should be performed promptly in patients who experience a carotid-territory event--ideally, within 24 hours (17). The urgency inherent in this recommendation is reinforced by newly published evidence demonstrating that the benefit of endarterectomy is highly time-dependent: Surgery is most effective when performed within 2 weeks of an ischemic event (number needed to treat [NNT] to prevent one stroke in 5 years = 5), and this benefit declines quickly over time (NNT = 125 for patients who underwent endarterectomy more than 12 weeks after an ischemic event) (19). It is also imperative to identify patients with TIA caused by cardiogenic brain embolism; for patients with atrial fibrillation, anticoagulation with use of warfarin reduces the risk of stroke by about 70% (20).

The value of neuroimaging

Neuroimaging performed after a TIA with CT scanning or magnetic resonance imaging (MRI) is helpful both diagnostically and prognostically. Published guidelines recommend neuroimaging, primarily to exclude structural pathology that can mimic TIA (eg, tumor, subdural hematoma, intracerebral hemorrhage). Patients with a TIA who have evidence of acute infarction on CT brain imaging are at a higher risk of recurrent stroke than those without evidence of infarction (21). In the acute stage of a TIA, however, most CT scans and conventional MRI sequences are unremarkable.

The increasing availability of diffusion-weighted MRI is a major advance. It is the most sensitive and specific diagnostic test, capable of revealing acute ischemic lesions in about 50% or more of patients who undergo scanning within 3 days of a TIA (22). (The likelihood of detecting such lesions is proportional to the duration of TIA symptoms and how quickly the scan is performed after symptom onset.)

Use of diffusion-weighted MRI has been shown to change diagnosis or treatment strategies in one third of cases (22) (figure 2). For risk stratification, diffusion-weighted MRI performed immediately after TIA may be the most powerful tool for predicting which patients are at high or low risk of a subsequent stroke. Furthermore, MRI is superior to CT scanning in providing detailed information about chronic silent cerebrovascular disease. Such data may help support the need for aggressive secondary prevention efforts in individual patients, since these patients are also at risk of vascular cognitive impairment (see article by Dr Black in this symposium). For example, in the Rotterdam study of an elderly population sample (23,24), the presence of small silent brain infarcts doubled the risk of dementia and tripled the risk of stroke over 4 years of follow-up. Use of magnetic resonance or CT angiography can noninvasively assess the presence and extent of arterial occlusive disease of the intracranial and extracranial circulation, including aortic arch atherosclerotic plaque.

Should TIA patients be admitted to hospital?

We know the value of hospital stroke units, but what about TIA units? Sadly, there are no trial data to guide us about the effectiveness of inpatient compared with outpatient management of a TIA or minor stroke. There exists in many institutions a bias against hospitalization of TIA patients because they do not "look" sick, and routine admission is not cost-effective.

This belief was recently challenged by Johnston and colleagues (25), who argued that brief hospitalization may actually be cost-effective because patients who are admitted after a TIA and have a stroke in the hospital may be more likely to be treated with thrombolytic therapy. Short-stay units have been established in some medical centers and should be considered for selected high-risk patients, especially when diagnostic tests will be delayed or difficult to obtain on an outpatient basis.

Potential benefits of hospital admission include the ability to:

• Expedite diagnostic investigations
• Encourage more accurate and timely diagnostic and treatment decisions and promote specialty consultations when diagnostic uncertainty exists
• Allow observation of patients whose condition may fluctuate or worsen and provide ready access to thrombolysis for suitable candidates who later experience a completed stroke (21)
• Facilitate surgical consultation or interventional neuroradiologic procedures for patients found to have symptomatic carotid artery disease
• Allow greater opportunity for patient and family education regarding diagnosis and new medications, risk factor assessment and modification (including smoking cessation), and encouragement of compliance with treatment recommendations

Furthermore, some patients who receive the diagnosis of TIA actually have persisting neurologic deficits (ie, a minor stroke). "Mild" deficits (eg, visual field defect, ataxia, gait or balance disorder, cognitive impairment) may not always be appreciated in the emergency department but may benefit from rehabilitation and safety assessments and therapy.

An alternative strategy to hospitalization is establishment of regional stroke-prevention outpatient clinics to accommodate urgent patient referrals from emergency departments or family medicine units. In Ontario, this approach is being implemented as part of a provincial reorganization of stroke services, and it is becoming a model for a national stroke strategy.

Conclusion

TIAs, like acute coronary syndromes, are high-risk, unstable conditions. The early risk of stroke after a TIA is higher than previously appreciated, and patients suspected of having experienced a TIA should be directed to the emergency department or urgent stroke clinic for rapid assessment and treatment. We need to overcome existing knowledge-practice gaps in TIA management and redouble our efforts to ensure optimal care for this high-risk population.

References

1. American Heart Association. Heart disease and stroke statistics--2004 update. Accessed Nov 2, 2004
2. Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000;284(22):2901-6
3. Gladstone DJ, Kapral MK, Fang J, et al. Management and outcomes of transient ischemic attacks in Ontario. Can Med Assoc J 2004;170(7):1099-104
4. Panagos PD, Pancioli AM, Khoury J, et al. Short-term prognosis after emergency department diagnosis and evaluation of transient ischemic attack (TIA). Acad Emerg Med 2003;10(5):432-3
5. Lovett JK, Dennis MS, Sandercock PA, et al. Very early risk of stroke after a first transient ischemic attack. Stroke 2003;34(8):e138-40. Accessed Nov 2, 2004
6. Coull AJ, Lovett JK, Rothwell PM; Oxford Vascular Study. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ 2004;328(7435):326
7. Hill MD, Yiannakoulias N, Jeerakathil T, et al. The high risk of stroke immediately after transient ischemic attack: a population-based study. Neurology 2004;62(11):2015-20
8. Eliasziw M, Kennedy J, Hill MD, et al, for the North American Symptomatic Carotid Endarterectomy Trial Group. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. Can Med Assoc J 2004;170(7):1105-9
9. Adams RJ, Chimowitz MI, Alpert JS, et al. Coronary risk evaluation in patients with transient ischemic attack and ischemic stroke: a scientific statement for healthcare professionals from the Stroke Council and the Council on Clinical Cardiology of the American Heart Association/American Stroke Association. Circulation 2003;108(10):1278-90
10. Johnston SC, Fayad PB, Gorelick PB, et al. Prevalence and knowledge of transient ischemic attack among US adults. Neurology 2003;60(9):1429-34
11. Nguyen-Huynh MN, Fayad P, Gorelick PB, et al. Knowledge and management of transient ischemic attacks among US primary care physicians. Neurology 2003;61(10):1455-6
12. Goldstein LB, Bian J, Samsa GP, et al. New transient ischemic attack and stroke: outpatient management by primary care physicians. Arch Intern Med 2000;160(19):2941-6
13. Edlow JA, Kim S, Emond JA, et al. US emergency department visits for transient ischemic attack, 1992-2000. Acad Emerg Med 2003;10(5):432
14. Albers GW, Caplan LR, Easton JD, et al, for the TIA Working Group. Transient ischemic attack--proposal for a new definition. N Engl J Med 2002;347(21):1713-6
15. Caplan LR. TIAs: we need to return to the question, 'What is wrong with Mr Jones?' Neurology 1988;38(5):791-3
16. Feinberg WM, Albers GW, Barnett HJ, et al. Guidelines for the management of transient ischemic attacks. From the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart Association. Circulation 1994;89(6):2950-65
17. Johnston SC. Clinical practice: transient ischemic attack. N Engl J Med 2002;347(21):1687-92
18. Josephson SA, Bryant SO, Mak HK, et al. Evaluation of carotid stenosis using CT angiography in the initial evaluation of stroke and TIA. Neurology 2004;63(3):457-60
19. Rothwell PM, Eliasziw M, Gutnikov SA, et al, for the Carotid Endarterectomy Trialists Collaboration. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004;363(9413):915-24
20. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet 1993;342(8882):1255-62
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(12):2894-8
22. Kidwell CS, Alger JR, DiSalle F, et al. Diffusion MRI in patients with transient ischemic attacks. Stroke 1999;30(6):1174-80
23. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348(13):1215-22
24. Vermeer SE, Hollander M, van Dijk EJ, et al; Rotterdam Scan Study. Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke 2003;34(5):1126-9
25. Johnston SC, Nguyen-Huynh MN. Is hospitalization after TIA cost-effective simply on the basis of treatment with tPA? (Abstr) Stroke 2004;35(1):245

Dr Gladstone, coordinator of this symposium, is director, Inpatient Stroke Services, and codirector, Regional Stroke Prevention Clinic, Sunnybrook and Women's College Health Sciences Centre, and lecturer, division of neurology, department of medicine, University of Toronto. Correspondence: David J. Gladstone, MD, FRCPC, Division of Neurology and Regional Stroke Centre, Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Ave, Suite A442, Toronto, Ontario M4N 3M5, Canada. E-mail: david.gladstone@sw.ca.

Symposium Index

• Commentary. TOWARD AN EMERGENCY RESPONSE TO TRANSIENT ISCHEMIC ATTACKS. By David J. Gladstone, MD, FRCPC
• VASCULAR DEMENTIA: Stroke risk and sequelae define therapeutic approaches. By Sandra E. Black, MD, FRCPC
• STROKE PREVENTION: MATCHing therapy to the patient with TIA. By Nicolas U. Weir, MD, MSc, MRCP, Andrew M. Demchuk, MD, FRCPC, Alastair M. Buchan, MB, FRCPC, Michael D. Hill, MD, MSc, FRCPC

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