The traditional view of transient ischemic attack (TIA) is that it is a “benign, reversible ischemic syndrome” with a lower risk of recurrence than cerebral infarction. However, recent studies have found that the risk of stroke in TIA patients is about 8% within 7 d, 10% within 30 d, and 10% to 20% within 90 d. The risk of recurrent stroke within 90 d in acute stroke is only 2% to 7%, and the total risk of recurrent TIA, myocardial infarction and death within 90 d is as high as 25%.
At present, the diagnosis and treatment of TIA in China are seriously underestimated and misdiagnosed, and the problems of untimely and unregulated treatment are prominent. In view of this, the editorial board of the Chinese Journal of Internal Medicine invited domestic neurologists to fully discuss and finally reach an expert consensus on the concept, pathogenesis, etiological stratification assessment and treatment decision of TIA.
I. Concept
1. Historical review: The traditional “time-based” concept of transient ischemic attack (TIA) originated in the 1950s and 1960s. In 1964, Acheson and Hutchinson supported the use of a 1-h time limit; Marshel suggested the use of the 24-h concept; in 1965, the Fourth Princeton Conference on Cerebrovascular Disease defined TIA as “sudden onset of focal or whole-brain neurological deficits lasting no more than 24 h and excluding non-vascular causes”.
The National Institutes of Health (NIH) classification of cerebrovascular disease adopted this definition in 1975 and has been used ever since.
However, with modern advances in imaging, the traditional definition based on “time and clinical” has been questioned. Studies have shown that the majority of patients with TIA have symptoms lasting less than 1 h. Patients with symptoms lasting longer than 1 h have little chance of recovering within 24 h, and some patients with full clinical recovery have imaging studies that suggest infarction.
The American TIA Working Group proposed a new concept of TIA in 2002: “an episode of transient also neurological deficit due to local cerebral or retinal ischemia, with typical clinical symptoms lasting no more than 1h and no evidence of acute cerebral infarction on imaging”. The new concept shortens the time limit of TIA to 1h and improves the definition of TIA and stroke from the traditional criteria of “time and clinical symptoms” to “histological damage” (Table 1).
2. Recommendation: TIA and cerebral infarction are different stages in the dynamic evolution of ischemic brain injury. It is recommended that the criteria of “histological injury” should be adopted as far as possible in hospitals where possible, and those with symptoms lasting for more than 1 h should be treated urgently according to the acute stroke process. If symptoms persist for more than 1 h and there is evidence of “histological injury”, TIA should no longer be diagnosed.
II. Pathogenesis
1. Literature review: It is generally accepted that the main etiology and pathogenesis of TIA are often divided into hemodynamic and microembolic types. The hemodynamic type of TIA is caused by distal transient cerebral ischemia due to blood pressure fluctuations on the basis of severe arterial stenosis. Microembolic TIA is subdivided into arterial-arterial origin and cardiac origin. Its pathogenesis is mainly based on the embolus of arterial or cardiac origin entering the cerebral arterial system causing vascular obstruction, and microembolic TIA is formed if the embolus is autolyzed.
2.Recommendation: TIA is a syndrome. Different etiologies determine different clinical decisions and have different prognoses. Therefore, attention should be paid to the etiology of TIA, and it is recommended that the clinical diagnosis of TIA should include its pathogenesis as much as possible.
III. Clinical evaluation and treatment decision
(I) Clinical evaluation recommendations
1. Active evaluation of risk stratification and early admission of high-risk patients: the results of studies on prognosis suggest [1] that the earlier the management of TIA patients should be, the better. Patients with initial or frequent TIA, symptom duration >1h, symptomatic internal carotid artery stenosis >50%, clear emboli of cardiac origin (e.g., atrial fibrillation), known hypercoagulable state, and high-risk patients with California score or ABCD score should be admitted to the hospital as early as possible (within 48h) for further evaluation and treatment.
2. New TIA should be treated as “emergency”: New TIA (within 48 h) indicates a high risk of stroke in the short term and should be treated as an important emergency.
3. Improve all relevant examinations as early as possible: Patients with suspected TIA should first undergo magnetic resonance diffusion imaging as much as possible to clarify whether it is a TIA. patients with TIA should be evaluated and examined urgently through fast emergency access (within 12 h). If a head CT, ECG or carotid Doppler ultrasound is not completed in the emergency, then the initial evaluation should be completed within 48h. If completed in the emergency department with negative results, the time of comprehensive evaluation can be extended appropriately to clarify the mechanism of ischemia occurrence and subsequent preventive treatment.
4.Comprehensive examination and assessment.
(1) General examination: The evaluation includes electrocardiogram, complete blood count, blood electrolytes, renal function and rapid glucose and lipid measurements.
(2) Vascular examination: Application of angiography (CTA), magnetic resonance angiography (MRA), and vascular ultrasound can detect important intracranial and extracranial vascular lesions. Whole brain angiography (DSA) is the gold standard for preoperative evaluation of carotid endarterectomy (CEA) and carotid artery stenting (CAS).
(3) Assessment of collateral circulation compensation and cerebral blood flow reserve: The application of DSA, cerebral perfusion imaging and/or transcranial color Doppler ultrasonography (TCD) to assess collateral circulation compensation and cerebral blood flow reserve is necessary to identify hemodynamic TIA and guide treatment.
(4) Examination of vulnerable plaque: vulnerable plaque is an important source of arterial emboli. Carotid vascular ultrasound, intravascular ultrasound, MRI and TCD microembolism monitoring are helpful for the evaluation of vulnerable plaques in atherosclerosis.
(5) Cardiac evaluation: In cases of suspected cardiogenic embolism, or in those under 45 years of age in whom neck and cerebral vascular examination and hematologic screening fail to clarify the etiology, transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE) are recommended and may reveal cardiac appendage thrombus, abnormalities of the atrial septum (atrial wall aneurysm, patent foramen ovale, atrial septal defect), mitral valve redundancy, and aortic arch multiple sources of emboli such as atherosclerosis.
(6) Other relevant tests based on medical history.
(II) Recommendations for treatment decisions
It is recommended to stratify the different etiologies and use different treatment decisions (Figure 2).
1. Internal treatment.
(1) Cardiogenic embolic TIA: In patients with TIA with persistent or paroxysmal atrial fibrillation, long-term oral warfarin anticoagulation is recommended (except in patients with infective endocarditis) with a target international normalized ratio (INR) of 2.5 (range 2.0 to 3.0). For patients with contraindications to anticoagulants, aspirin (75-150 mg/d) is recommended, and if aspirin is not tolerated, clopidogrel (75 mg/d) is applied. In the absence of a high risk of other cardiogenic embolism, anticoagulants should not be used in patients with TIA in sinus rhythm.
(2) Non-cardiogenic embolic TIA: oral anticoagulants are not recommended [9-10]. They are recommended for long-term antiplatelet therapy. The commonly used drug is aspirin (75-150 mg/d), and there are also data that clopidogrel (75 mg/d) is more effective than aspirin. In those with definite arterial-arterial embolicity, treatment includes antiplatelet aggregation, plaque stabilization and intensive statin therapy (LDL-C target value of 2.1 mmol/L or less). Some data suggest that the combination of aspirin (75-150 mg/d) and clopidogrel (75 mg/d) may be more effective.
(3) Hemodynamic TIA: In addition to antiplatelet aggregation and lipid-lowering therapy, antihypertensive drugs and vasodilators should be discontinued, and if necessary, volume expansion therapy should be given, and endovascular or surgical treatment can be considered in hospitals with conditions. In the case that the aortic stenosis has been released, blood pressure control to below the target value can be considered.
(4) Control of risk factors: The control of various risk factors for TIA should be strengthened, see the US guidelines for specific recommendations.
2.Surgical and endovascular treatment.
(1) Extracranial carotid atherosclerotic stenosis: According to the NASCET (North American Symptomatic Carotid Endarterectomy Trial) measurement criteria, symptomatic severe carotid stenosis is 70% to 99% in patients with new (within 6 months) TIA, if the patient is between 40 and 75 years of age ( life expectancy of at least 5 years), CEA or CAS can be performed in hospitals where available (perioperative stroke and death event rate < 6%).
Patients with new ischemic stroke or TIA and moderate symptomatic carotid stenosis (50% to 69%) are recommended to undergo CEA or CAS depending on their specific condition (age, sex, co-morbidities and severity of symptoms at the time of the attack or if the best medical treatment has failed); CEA or CAS is not indicated in cases of stenosis <50%. The treatment is recommended to be performed within 2 weeks in patients with TIA who have indications for CEA or CAS. For patients with symptomatic carotid occlusion, intracranial and extracranial vascular bypass surgery is not recommended.
(2) Atherosclerotic stenosis of the vertebrobasilar/intracranial arteries: For patients with atherosclerotic TIA of the vertebrobasilar or intracranial artery stenosis, endovascular treatment can be considered in hospitals where available if medical treatment (antithrombotic drugs, statins and other risk factor control treatments) has failed.