Transient Ischemic Attack

Etiology

TIA subtypes, classified according to the pathophysiological mechanisms, are similar to ischemic stroke subtypes. They include large artery atherothrombosis, cardiac embolism, small vessel (lacunar), cryptogenic, and uncommon subtypes such as vascular dissection, vasculitis, etc. The common risk factors for all TIA include diabetes, hypertension, age, smoking, obesity, alcoholism, unhealthy diet, psychosocial stress, and lack of regular physical activity. A previous history of stroke or TIA will increase substantially the subsequent risk of recurrent stroke or TIA.[4][5] Among all risk factors, hypertension is the most important one for an individual as well as in a population.

Epidemiology

TIA incidence in a population is difficult to estimate due to other mimicking disorders, but TIA incidence in the United States could be around half a million per year, and estimates are about 1.1 per 1000 in the United States population. The estimated overall prevalence of TIA among adults in the United States is approximately 2%. It has been shown that previous stroke history increases the prevalence of TIA. Few studies have shown that the majority of people who presented with initial stroke had prior TIA symptoms.[4]

Pathophysiology

The pathophysiology of TIA depends on the subtype as follows. The common issue is the transient interruption of arterial blood flow to an area of the brain supplied by that particular artery.

• Large artery atherothrombosis. This may be intracranial or extracranial atherothrombosis. The mechanism may be a lack of blood flow distal to the site of arterial stenosis or an artery-to-artery embolism, the more common mechanism.
• Small vessel ischemic diseases. The underlying pathology is either lipohyalinosis or small vessel arteriolosclerosis. The commonest risk factor is hypertension, followed by diabetes and age.
• Cardiac embolism. A clot in the cardiac chamber, most commonly in the left atrium, is secondary to atrial fibrillation.
• Cryptogenic. This is usually a cortical pattern of ischemia without any identifiable large artery atherothrombosis or cardiac source of emboli. More recently it is often referred to as ESUS (embolic stroke of unknown source).
• Other uncommon causes such as arterial dissection or hypercoagulable states. 

History and Physical

TIA symptoms have often resolved by the time the patient presents to her doctor or emergency department. The history of present illness should include onset, duration, timing, complete neurological symptoms, associated symptoms, and any aggravating or relieving factors. The clinician should also try to identify the associated risk factors such as coronary artery disease, smoking, drug abuse, obesity, diabetes mellitus, dyslipidemia, and hypertension, as well as personal or family history of hypercoagulability disorders, stroke, or TIA. The history should include etiological clues such as a history of atrial fibrillation and recent myocardial infarction to suggest a cardioembolic source; transient loss of vision like a curtain rising or descending will suggest an internal carotid artery problem. The presence of any cortical symptoms, such as language disturbance or visual field loss, will point to a cortical TIA rather than a lacunar syndrome. 

Physical examination should focus on identifying focal neurological deficits and speech disturbances, which are the most common presenting symptoms in patients with TIA. Cranial nerve examination can yield findings of monocular blindness, disconjugate gaze, facial droop, hemianopia, diplopia, abnormal tongue movement, difficulty swallowing, and auditory dysfunction. Some of the motor findings include unilateral weakness in the upper or lower extremities, face, and tongue, increased tone, clonus, rigidity and also abnormal reflexes that could occur with TIA. Cardiac examination and carotid auscultation for a carotid bruit are very important. Fundoscopy is important to look for any fundoscopic evidence of vascular changes as a result of hypertension or diabetes. It may also show a Hollenhorst plaque, which will indicate an underlying internal carotid artery disease.

Evaluation

The goals of the evaluation of TIA are

1. To prove the vascular origin of the symptoms either directly or indirectly. This means to find evidence of hypoperfusion and/or acute infarction or identify a presumptive source such as a large-vessel stenosis.
2. To exclude an alternative nonischemic origin
3. To determine the underlying vascular mechanism, for example, large-vessel atherothrombotic, cardioembolic, and small-vessel lacunar. This determination allows for selecting the optimal therapy for secondary prevention of TIA pr stroke.
4. To identify prognostic outcome categories.

The 2009 AHA/ASA guidelines include "neuroimaging within 24 hours of symptom onset and further recommend MRI and diffusion-weighted MR imaging as preferred modalities." A head CT, preferably with a CT angiogram, is recommended if an MRI cannot be performed. Brain MRI with diffusion-weighted imaging has a greater sensitivity than CT for detecting small infarcts in patients with TIA. The practitioner should assess the patient's cervicocephalic vasculature for atherosclerotic lesions using carotid ultrasonography/transcranial Doppler ultrasonography, magnetic resonance angiography, or CT angiography. These lesions are treatable. In candidates for carotid endarterectomy, carotid imaging should be performed within 1 week of the onset of symptoms. Cardiac assessment should be done with ECG, Echocardiogram/TEE  to find a cardioembolic source and the presence of patent foramen ovale, valvular disease, cardiac thrombus, and atherosclerosis. Holter monitor or more prolonged cardiac rhythm monitor in the outpatient setting is reasonable for patients with cortical infarction without any clear source of emboli, primarily to evaluate for paroxysmal atrial fibrillation. Routine blood tests, including complete blood count (CBC), PT/INR, CMP, FBS, lipid panel, urine drug screen, and ESR, should be considered.[6][7][5].

National Stroke Association has established guidelines for TIA evaluation as follows in 2006:[8]

CBC = complete blood countCEA = carotid endarterectomyTCD = transcranial Doppler TEE = transesophageal echocardiogramTTE = transthoracic echocardiogram

The ABCD2 score is very important for predicting subsequent risks of TIA or stroke. The ABCD2 score was derived from providing a more robust prediction standard. The ABCD2 score includes age, blood pressure, clinical symptoms, duration, and diabetes.

• Age: older than 60 years (1 point)
• Blood pressure greater than or equal to 140/90 mmHg on first evaluation (1 point)
• Clinical symptoms: a focal weakness with the spell (2 points) or speech impairment without weakness (1 point)
• Duration greater than 60 min (2 points) or 10 min to 59 min (1 point)
• Diabetes mellitus (1 point).

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. Most stroke centers will admit patients with TIA to the hospital for expedited management and observation if the score is 4, 5, or higher. For patients with a lower score, expedited evaluation and management are still warranted. This expedited approach has been proven to improve the outcome.[9]

Treatment / Management

The main aim of treatment of TIA is to decrease the risk of subsequent stroke or TIA. Early treatment after a TIA can significantly reduce the risk of early stroke. Post TIA, the risk of stroke within 3 months has been reported to be around 20%, with approximately 50% of these strokes occurring within the first 2 days after the initial presentation. Evaluating the vessel status and looking for atrial fibrillation when a patient comes with TIA is extremely important. This will significantly reduce future strokes. Management of TIAs should focus on treating underlying etiologies.[10][11][12](A1)

Studies in the new millennium already confirmed the importance of expedited evaluation and treatment plus the polytherapy approach. The EXPRESS study in the UK has shown the importance of early intervention versus regular treatment by reducing 80% of the stroke risk. [13] Hackam et al. did a meta-analysis in 2007 showing that a combination of diet, exercise, antiplatelet, statin, and antihypertensive therapy may reduce the subsequent stroke by 80% to 90%.[14]

More recent studies in China (CHANCE trial) and the multinational POINTE trial also confirmed dual antiplatelet with aspirin and clopidogrel for 3 weeks to 1 month, followed by a single antiplatelet agent, is the best scheme for antiplatelet therapy. [15][16](B3)

The other part of the treatment will depend on the underlying etiology of the TIA. Revascularization is recommended for symptomatic cervical internal carotid artery stenosis of 70% or higher. Carotid endarterectomy may have a slight benefit-to-risk ratio compared with endovascular intervention and stenting. Whether to operate on patients with 50-69% stenosis will depend more on the surgeon's complication rates, given the vast improvement in the efficacy of aggressive medical therapy. The SAPPRIS trial showed that endovascular Wingspan stenting of 70-99% stenosis of intracranial major arterial stenosis is not better than aggressive medical therapy alone. [17](A1)

Oral anticoagulation is indicated for patients with atrial fibrillation or other sources of cardioembolic sources of TIA.

Differential Diagnosis

• Carotid artery dissection

• Meningitis

• Meningococcal meningitis

• Multiple sclerosis

• Stroke, ischemic

• Stroke, hemorrhagic

• Subarachnoid hemorrhage

• Syncope

Staging

Risk Stratification Scores

Several risk stratification scores have been developed to help physicians manage patients with a TIA. One widely used score is the ABCD2 score:

A= Age more than 60 years / Score 1

B= SBP> 140 or DBP> 90 / Score 1

C= Clinical features:

Speech impairment without weakness / Score 1

Weakness with/without speech impairment / Score 2

D= Duration

More than 60 mins / Score 2

Between 10-59 mins / Score 1

D= Diabetes / Score 1

Patients with an ABCD2 score of 6-7 have an 8% risk of stroke within 48 hours.

Patients with an ABCD2 score of less than 4 have a 1% risk of stroke within 48 hours.

Even though scales are important in the evaluation of TIA, be aware that patients with critical carotid artery stenosis may sometimes present with a very low ABCD2 score.