Transient Ischaemic Attacks (TIA)

A transient ischaemic attack is a temporary inadequacy of the circulation in part of the brain (a cerebral or retinal deficit) that gives a clinical picture similar to a stroke except that it is transient and reversible. Hence TIA is a retrospective diagnosis. The duration is no more than 24 hours and a deficit that lasts longer than 24 hours is defined as a stroke. The majority are less than 30 minutes.

The aetiology may be thrombotic but usually it is embolic. Haemorrhage is unlikely to produce a reversible lesion.

• The incidence is 42 per 100,000 population and it is commoner with increasing age.
• It is rare under the age of 60.
• The incidence is decreasing,¹ perhaps as hypertension is better controlled.
• It affects men more than women and black races are at greater risk.
• About 15% of first stroke victims have had a preceding TIA.

It has the same risk factors as for stroke. These are similar to risk factors for CHD, as discussed in Primary prevention of cardiovascular disease and Secondary prevention of IHD, except that cholesterol is less important but still significant and blood pressure is even more important. This is discussed in Stroke prevention.

Usually Thromboembolism:

• It affects the carotid area in about 80% and the vertebrobasilar area in about 20%. The efficacy of collateral flow through the Circle of Willis is often much less than may be expected from the basic anatomy, especially with advancing years.
• The commonest source of emboli is the carotids, usually at the bifurcation.
• They can originate in the heart with atrial fibrillation particularly, with mitral valve disease, or aortic valve disease, or from a mural thrombus forming on a myocardial infarct or a cardiac tumour, usually atrial myxoma.
• The vertebrobasilar arteries may be a source.
• Occasionally there is paradoxical embolism originating from the right side of the circulation.
• Haemodynamic TIAs are rare. There is not necessarily total occlusion of the arteries and circulation may merely be inadequate. Sometimes spasm may be involved but this is difficult to ascertain.

A TIA may last anything from a few minutes to 24 hours. The usual duration is about 10 to 15 minutes. Onset is over a few minutes.

There may be changes in behaviour that are best described by a third party.

The clinical features will depend upon the part of the brain that becomes ischaemic:

Carotid territory (80%)

• Symptoms are usually unilateral and most often affect the motor area causing unilateral weakness, affecting an arm, leg, or one side of the face. There may be dysarthria.
• There may be sensory symptoms in the same areas.
• If Broca's area is involved there will also be difficulty with speech, called Broca's dysphasia. This produces inconsistent and unpredictable errors, usually substitution, with spontaneous speech containing fewer errors. This is a great simplification and the matter is discussed more fully in Dysarthria and dysphasia.
• There may be Amaurosis Fugax (fleeting loss of vision), a unilateral loss indicative of retinal ischaemia usually associated with emboli or stenosis of the ipsilateral carotid artery.

Vertebrobasilar territory (20%)

• If the ophthalmic cortex is involved there will be a homonymous hemianopia that may present purely as ignoring one side of the visual field.
• There may be bilateral blindness.
• There may be hemiparesis, hemisensory symptoms, diplopia, vertigo, vomiting, dysarthria, dysphagia, or ataxia.
• Ask both the patient and, if possible, those around about weakness such as a drooping face, gait, confusion, dysarthria, loss of memory or abnormal behaviour. Fleeting symptoms may be more obvious to those around than to the patient.
• Ask about duration, intensity and fluctuation of symptoms.
• Were there any simultaneous cardiac symptoms?

• Has this happened before?
• Has there been recent surgery especially on the heart or carotids?
• Has there been a previous stroke or any CHD?
• Is hypertension being treated?
• Is there known diabetes?
• Are there any other significant illnesses? There may be a hypercoaguable state or vasculitis such as temporal arteritis.
• If it presents in a person much younger than 60 ask about drug abuse, especially cocaine.

Neurological examination should be performed as for a stroke but by the time the patient is seen it may have reverted to normal.

• Note overall attentiveness, ability to cooperate and verbal fluency
• Examination of the pulse may reveal abnormality of rate or rhythm. The artery may feel hard and rigid.
• Check blood pressure in both arms.
• Listen for a carotid bruit at the bifurcation and the base of the neck for a vertebral bruit. However, a bruit can occur with minimal stenosis and significant occlusion may be silent.
• Check peripheral pulses.

The patient will need to be referred to a specialist centre within 7 days but some of the investigations should be carried out before referral.

Primary care

• Check urine for glucose
• FBC,ESR
• U&E, fasting lipids and glucose
• Coagulation studies (especially in younger patients)
• Antiphospholipid antibodies
• ECG may show atrial fibrillation, myocardial infarction or simply evidence of ischaemia.

Secondary care

The following are likely to be requested from the specialist service:

• If there is suggestion of problems with the heart, including AF, echocardiogram may show atrial thrombus, aneurysm of the anterior wall of the left ventricle with mural thrombus, atrial myxoma or left side valve disease.
• Cardiac monitoring may show paroxysmal AF.
• Doppler studies of the carotid and vertebral arteries may show narrowing. This investigation may be followed by carotid angiography and carotid endarterectomy if stenosis is a least 70%
• CT or MRI of the brain may show an area of reduced blood flow or an unsuspected infarct. MRI tends to be more sensitive and to give better images of carotid and vertebral arteries. It may also demonstrate the rare CADASIL.
• It may be argued that full investigation for CHD should be initiated as the commonest cause of death after TIA is myocardial infarction.

• Before there is full recovery it is impossible to differentiate from a stroke
• Intracranial lesion (tumour or subdural haematoma). Beware of diagnosing TIA if there has been loss of consciousness or convulsion
• Todd's paralysis follows a seizure and is characterised by a temporary, usually unilateral paralysis. It may also affect speech or vision and usually resolves within 48 hours. The cause is unknown
• Syncope due to cardiac arrhythmia
• Temporal arteritis (also called giant cell or cranial arteritis) has a very high ESR, there is often thickening and tenderness of the temporal artery and monocular, temporary blindness is a frequent presentation
• Migraine, or migrainous aura
• Retinal or vitreous haemorrhage
• Focal epileptic seizure
• Labyrinthine disorders
• Transient global amnesia
• Psychological disorders (including hyperventilation)
• Metabolic disturbance (e.g. hypoglycaemia)

Features that do not fully fit for TIA are called transient neurological attacks or TNA. The risk of subsequent stroke is not as high as for TIA but the risk for cardiac events is higher.²

The following do not suggest a TIA:

• Isolated confusion
• General weakness
• Isolated dizziness
• Falls
• Isolated amnesia
• Fainting
• Isolated tinnitus
• Scintillating scotoma

The following may possibly be associated with a TIA:

• Vertigo
• Diplopia
• Dysarthria
• Dysphasia
• Loss of balance
• Isolated sensory symptoms affecting face or limbs on one side
• Drop attack

Anyone who has had a single TIA must not drive for 1 month. The patient must inform the insurance company. Those with multiple TIAs over a short period of time must inform the DVLA and their insurance company. They will probably be barred for 3 months.

Antiplatelet therapy and anticoagulation

• If the patient is in atrial fibrillation, management of that condition is required. In persistent AF there is benefit from anticoagulation but this is not seen in the absence of AF.³
• If BP is raised it must be brought under control. There is still some controversy about reduction of blood pressure in the acute phase. A study of TIA and stroke from Vienna found that spontaneous or therapeutically induced decrease of the diastolic blood pressure by more than 20 mmHg was associated with a three-fold risk of an "unfortunate functional outcome."⁴
• If not already on aspirin, it should be started. Most people would advocate 300mg daily but whether there is really any difference between 300, 150 and 75mg daily is unproven, nor has the risk of bleeding been proven to be dose dependent. There has been no evidence to show that any formulation has a lesser risk, so the cheapest, dispersible aspirin, is recommended. Expert opinion tends to recommend 300mg.
• If there is gastric intolerance of aspirin a PPI is recommended. If there are genuine reasons for avoiding aspirin such as allergy, clopidogrel is suggested.
• If the patient already takes aspirin there is evidence of further benefit by adding dipyridamole⁵ but a Cochrane review found that dipyridamole, alone or with aspirin, gave no benefit.⁶
• Other drugs for those already on aspirin or for whom it is contraindicated include ticlodipine and clopidogrel. Heparin may be beneficial. It does not actively lyse thrombus or embolus but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis. Warfarin is drug of choice in atrial fibrillation.⁷ For crescendo TIA the advice is to replace aspirin by clopidogrel 75 mg orally once a day or ticlopidine 250 mg orally twice a day.
• Ticlopidine has been proven to be more effective than aspirin, but it has serious side effects that make it unsuitable for long term use. Clopidogrel is more effective than aspirin and at least as safe.
• The combination of clopidogrel plus aspirin is said to represent the likely future therapy for high-risk patients,⁸ but there is some concern about the risk of bleeding with these drugs together.
• Intravenous antiplatelet therapy with glycoprotein IIb/IIIa inhibitors for acute stroke and as an adjunct to carotid artery stenting appears promising. The role in TIA is less certain.

Other risk factors

• If cardiac disease is found it must be managed.
• Diabetes, if present, must be well controlled.
• Cessation of smoking is imperative.
• Reducing obesity and encouraging exercise is advocated in a review of management of modifiable risk factors.⁹
• CREST suggests that a statin should be started whilst awaiting the results of lipid profiles. Bearing in mind that the next few days are critical and that statins seem to have a stabilizing effect on atheroma, this seems wise advice.
• The outcome of individual cases is so variable that it may seem advisable to admit them all to hospital.¹⁰ However, this is not the policy of either the Royal College of Physicians or Clinical Knowledge Summaries but both insist on assessment within a week.

All the risk factors in the article on stroke prevention must be addressed. Energetic management of blood pressure and cholesterol is important to reduce subsequent mortality and morbidity from stroke and CHD.¹¹ The PROGRESS trial (Perindopril pROtection aGainst REcurrent Stroke Study)showed that treatment with an ACE inhibitor and thiazide produced larger blood pressure reductions and larger stroke reductions than monotherapy with perindopril alone. It recommended that treatment with these two agents should be considered routinely for all patients with a history of previous stroke or TIA, whether hypertensive or normotensive.¹²

Risk factors must also be addressed in the elderly.¹³

Carotid stenosis

The SIGN guidelines from 1997 on management of a patient with stroke¹⁴ emphasises that clinical signs such as a carotid bruit should not be relied upon to diagnose carotid artery occlusion as they can be present in mild stenosis and absent when it is severe. They recommend non-invasive imaging such as carotid duplex or MRI angiography. Severe carotid stenosis is defined as an occlusion of at least 70% of the lumen. Carotid endarterectomy can reduce stroke by 48% with a less than 5% risk of operation causing death or disabling stroke. Over a 2 to 6 years follow up period the number needed to treat to prevent severe disabling stroke of death was 15 whilst the number needed to treat to cause harm by operation causing death or disabling stroke was 45. Risks are increased by other serious medical conditions including unstable angina, uncontrolled heart failure, COPD and malignancy. Where there is also significant coronary occlusion it is uncertain whether CABG or carotid endarterectomy should be performed first.

Carotid angioplasty may possibly be an acceptable alternative to endarterectomy but so far results are limited with very wide confidence limits.¹⁵

The College makes a number of recommendations.¹⁶

• TIA is not fatal but it is indicative or underlying atheroma.
• There is a strong risk of fatality if it progresses to a full stroke or if associated diseases such as myocardial infarction occur.
• Risk of stroke in first month after TIA is 5%.
• Risk of stoke in first year after TIA is 10%.
• Annual risk during next 4 years is 7% (7 times normal risk).¹
• Risk is greater with frequent TIAs, cerebral rather than ocular events, and severe carotid stenosis.

In a large study of 1,707 patients with TIA in California, over 10% returned to the emergency department with a stroke within 90 days but half of these returned within 2 days. 5 factors were independently associated with stroke. These were:¹⁷

• Age over 60
• Diabetes
• Symptoms longer than 10 minutes
• Weakness
• Impairment of speech

CREST suggests a scoring system called ABCD:

The patient may have made a full recovery but secondary prevention of TIA is very important and most of the issues covered in the Qualities and Outcomes Framework (QOF), relating to stroke also apply to TIA. Modifiable risk factors must be addressed.⁹

• If there is atrial fibrillation or another source for systemic emboli this must be addressed. The relative merits of the various approaches to the management of AF are discussed elsewhere. Anticoagulation is usually required if the rhythm cannot be converted but anticoagulants are of no value in the absence of AF.³
• BP must be controlled. The target should be no more than 140/90 according to NICE although the British Hypertension Society recommends 140/85. If the patient is diabetic the respective figures are 140/80 and 130/80.
• Everyone should be on antiplatelet medication of some sort. This is usually aspirin.
• Diabetes, if it exists, must be well controlled.
• Hyperlipidaemia must be addressed, not just for stroke but there is also a high risk of CHD. The NSF for coronary heart disease suggests starting a statin if total cholesterol is greater than 5mmol/l but the RCP, based on a trial by the Heart Protection Study Collaborative Group¹⁸ puts that figure as low as 3.5. A Cochrane review was unimpressed at the value of statins in preventing stroke but it did acknowledge that such patients were also at great risk of CHD.¹⁹
• If the patient smokes this must stop. Help may be offered.
• The obese should lose weight.
• A healthy diet should be advised.
• Exercise should be encouraged.²⁰