Section 1: Epidemiology and aetiology
The assumption when the definition was written was that this meant there was no permanent structural brain damage. The analogy would have been angina pectoris and MI.
However, with increasingly sensitive brain imaging, it has been realised that many patients with TIA, even when the symptoms last just a few minutes, have ischaemic damage, so the justification for having a separate diagnosis of TIA and stroke ceases to have much coherence.
Many stroke physicians would prefer to drop the diagnosis and call all such attacks stroke.
Every year in England, approximately 20,000 people will experience their first TIA,1 with an incidence rate of 0.5 in 1,000.
A large proportion of TIAs go unrecognised, with about half never coming to medical attention.2
Unfortunately, many major strokes are preceded by TIAs that have either not been recognised in time, or not been effectively treated.
The care of patients with TIA has improved dramatically in the past decade, with work focusing on early recognition and prevention of more disabling events. An understanding of the different mechanisms is crucial for treatment and prevention.
The aetiology and epidemiology of stroke and TIA are identical. Most TIAs are due to ischaemia, but it is important to remember that a small primary intracerebral haemorrhage can occasionally present with transient symptoms.
Large-artery events are caused by lesions in the internal carotid artery, anterior or middle cerebral arteries, or in the posterior circulation in the vertebral or basilar territories. Any obstruction at these sites can cause
TIA symptoms, especially if collateral circulation is inadequate. Embolic events usually arise from a process starting from an extracranial large artery or from the heart, and occasionally from smaller vessels within the brain. Cardiac causes are most commonly secondary to AF or left ventricular disease.
Lacunar or small-vessel events are due to stenosis of one of the intracranial vessels, anteriorly from the middle cerebral artery or its branches and posteriorly from the vertebrobasilar system. The process involved is usually atherosclerosis driven by risk factors, such as hypertension and hypercholesterolaemia.
Section 2 Making the diagnosis
A diagnosis of TIA warrants urgent specialist assessment. The assumption should be that if there are persisting symptoms or signs, the diagnosis is stroke, not TIA, and the patient should be taken to hospital.
TIA symptoms result from a sudden change in vascular dynamics, so are of sudden onset. Four questions (see box 1) will determine whether the diagnosis is likely to be TIA.
Symptoms lasting a few seconds, or recurrent, frequent, stereotypical events, are unlikely to be due to TIA.
Conditions that mimic TIA include seizures, sepsis, delirium, hypo- and hyperglycaemia, migraine, space-occupying lesions and functional disorders.
Symptoms and signs
Carotid artery territory TIA symptoms include unilateral weakness or numbness, speech disturbance and visual defects, such as hemianopia or amaurosis fugax.
Vertebrobasilar territory symptoms include ataxia, articulation difficulty, diplopia, bilateral visual loss and hemianopic visual defects.
Isolated vertigo, syncope or amnesia are rarely thought to be caused by TIA, although a paper from the Oxford Vascular Study reporting on a consecutive series of patients with definite vertebrobasilar territory stroke found many with non-focal brainstem symptoms, such as vertigo and transient generalised weakness, in the preceding weeks.3
Patients with suspected TIA should receive aspirin immediately unless strongly contraindicated, and have initial basic investigations, most importantly blood glucose and ECG.
If the patient is in AF, an urgent brain scan is needed to exclude haemorrhage. They should be started on an immediate-acting anticoagulant.
The ABCD2 score (see table 1) offers guidance on stroke risk – many stroke services stratify TIA management into high risk (ABCD2 >4; see, investigate and assess in under 24 hours) or low risk (ABCD2 <4; see, investigate and assess within one week).4
Further investigations are based on risk stratification and exclusion of differential diagnoses. This includes a full blood work-up and possible brain imaging. Diffusion-weighted MRI is the modality of choice.
If MRI is not possible, CT can be especially useful in identifying haemorrhage and space-occupying lesions. Not all TIA referrals need brain imaging – it is only needed if the diagnosis is in doubt and the findings will influence management.
There is no need to image the carotid arteries unless surgery would be considered if significant stenosis were to be identified.
Section 3 Managing the condition
It is essential for all patients to have aggressive risk factor management (see box 2). Lifestyle advice should target as many of the risk factors as possible.
Patients in whom TIA is suspected must be advised not to drive for one month or until further discussion in a TIA clinic.
Treatment with antiplatelets, antihypertensives and statins has been shown to reduce the stroke rate if introduced early.5
Aspirin in patients with previous TIA or stroke has been shown to reduce the risk of vascular events by 13%.6
Aspirin 300mg once daily should be started while investigations are pending. TIA can occasionally be due to a small intracerebral haemorrhage, but this is uncommon and it is reasonable to start an antiplatelet without brain imaging.
The NICE recommendations for antiplatelet therapy after stroke are long-term combination of aspirin 75mg once daily (or clopidogrel if aspirin is not tolerated) and dipyridamole modified release 200mg
However, most stroke physicians see no reason to adopt a different approach to antiplatelet therapy in TIA from that for stroke. The National clinical guideline for stroke 2012 supports the use of clopidogrel first-line after TIA, only using the aspirin and dipyridamole combination if the patient cannot tolerate clopidogrel.
The CHANCE trial7 tested whether dual treatment with aspirin and clopidogrel started at day one after symptoms and continued for 90 days was superior to aspirin alone in minor stroke. It showed a significant reduction, from 11.7% to 8.2%, in progression to stroke, with no increase in haemorrhage rate.
This strategy is being adopted in neurovascular clinics, particularly in patients at very high risk, such as those with crescendo angina.
Antihypertensive treatment is recommended for the prevention of recurrent stroke and other vascular events following TIA.
The absolute BP target should be individualised (more rigorous control in patients with diabetes). Observational studies and clinical trials support BP reduction for secondary prevention, regardless of initial BP.
Although the optimal regimen remains uncertain, data from trials such as PROGRESS support the use of diuretics and the combination of diuretics and ACE inhibitors.8 However, it seems reasonable to follow
the latest NICE hypertension management guidelines.9
Statins, diabetes, smoking
Cholesterol-lowering drugs have been shown to be beneficial for primary and secondary prevention.10 This should be addressed by dietary modification and use of a statin if total cholesterol is >3.5mmol/L.
Tight glucose control is important in patients with diabetes with TIA or ischaemic stroke, to reduce micro- and macrovascular complications. HbA1c should be optimised to <53mmol/mol. Smoking raises the risk of stroke by about 50%. All TIA and ischaemic stroke patients should be supported to stop smoking.
Carotid endarterectomy is indicated in patients with TIA or stroke with a symptomatic carotid stenosis
of 70% to 99%. Surgery needs to be performed as soon as possible after the TIA; evidence suggests that by 12 weeks, drug treatment is as effective as surgery in preventing recurrence.11
AF contributes to about 20% of ischaemic strokes and TIA. Anticoagulation with warfarin has been the mainstay for patients with a CHADS-VASc score of >1, but for many, non-vitamin K antagonist oral anticoagulants (NOACs) offer easier, more reliable anticoagulation.
Patients should be given the choice between warfarin and a NOAC. Aspirin has no role in preventing stroke in patients with AF.
If an anticoagulant is not used, nothing useful can be achieved by treating with an antiplatelet.12
Section 4 Prognosis
More than 20% of strokes are preceded by a TIA, although this is often not noticed and reported by the patient.13
The prognosis for TIA and stroke is related to a timely diagnosis, referral to a specialist service and initiation of treatment, including secondary prevention.
The effect of urgent treatment of TIA and minor stroke on early recurrent stroke (EXPRESS) study suggested that rapid assessment and treatment, with the patient being seen the same day in clinic and having medication initiated there, reduced the risk of recurrence or development of stroke by up to 80%.5
Although a TIA should not have any long-term impact on patients’ daily activities, they must stop driving for a month.
Section 5 Case study
This case illustrates how TIA and stroke overlap, and even if symptoms have resolved, this does not mean management should be taken any less seriously than in a patient with persisting symptoms and signs.
A 58-year-old man was brought to A&E by his family.
During his morning walk, he noticed a sudden onset of left facial numbness and a dull headache
on the right posterior aspect. He was staggering and nauseated.
He telephoned his wife, who noticed his speech was slurred, but he had no word-finding difficulty.
There was a history of hypertension, hypercholesterolaemia, IHD (MI and percutaneous coronary intervention with bare metal stent in 2007) and probable TIA at the time of the cardiac intervention. His medication included antihypertensives, simvastatin, aspirin and clopidogrel.
When reviewed by A&E staff three hours after the onset of symptoms, his speech and balance had returned to normal. Examining his cardiovascular, respiratory and neurological systems revealed no abnormalities.
The history and examination were consistent with a TIA in the vertebrobasilar circulation. ECG showed sinus bradycardia with no ischaemic changes. The chest X-ray and blood tests were unremarkable and his random cholesterol was 6mmol/L. His BP was slightly elevated, at 160/80mmHg.
The patient’s ABCD2 score was four (moderate risk of stroke in the following 48 hours), so he was admitted to the stroke unit.
A diffusion-weighted brain MRI scan (pictured above) revealed an area of restricted diffusion in keeping with ischaemia in the posterior inferior cerebellar artery (PICA) territory. There was also some suggestion that the right vertebral artery might be occluded, so an outpatient CT angiogram was organised, mainly to exclude vertebral artery dissection.
The TIA diagnosis was explained to the patient and he was discharged with appropriate secondary prevention to reduce the risk of stroke. He was also instructed not to drive for one month.
Section 6 Evidence base
- Rothwell PM, Giles MF, Chandratheva A et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet 2007; 370: 1432-42 This study suggested the 90-day risk of fatal or disabling stroke was reduced by 80% with urgent specialist clinic review.
- PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033-41
Over the four-year observation period, active treatment reduced the risk of total major vascular events by 26%. Combination treatment with perindopril and indapamide reduced the risk of stroke by 43%. Treatment of patients with stroke with these two agents should be considered even when normotensive.
- Amarenco P, Bogousslavsky J, Callahan A III et al. High-dose atorvastatin after stroke or TIA. N Engl J Med 2006; 355: 549-59
This was the first trial to investigate the effect of cholesterol control with statins in patients with previous stroke or TIA and a normal cholesterol level. There was a significant reduction in cholesterol levels with treatment, and analysis of these data has reflected a reduction in stroke risk and favourable outcome.
- European Atrial Fibrillation Trial (EAFT) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after TIA or minor stroke. Lancet 1993; 342: 1255-62 EAFT recruited 455 patients from 108 centres in a randomised trial. It suggested warfarin was superior to placebo or aspirin in the prevention of stroke in patients with AF.
- Wang Y, Wang Y, Zhao X et al. Clopidogrel with aspirin in acute minor stroke or transient ischaemic attack. N Engl J Med 2013; 369: 11-19
This trial randomised 5,170 patients with non-disabling stroke or TIA to either aspirin alone or a combination of aspirin and clopidogrel. Treatment was started within 24 hours of onset of symptoms and continued for 90 days. Recurrence was significantly lower in the dual antiplatelet group (11.7% versus 8.2%) than in the aspirin alone group.
- Intercollegiate Stroke Working Party. National clinical guideline for stroke 2012 (fourth edition).
- Stroke Association stroke.org.uk/professionals
- European Stroke Organisation eso-stroke.org
- Contributed by Dr Oenone Poole-Wilson, registrar, and Professor Anthony Rudd, professor, stroke medicine, Guy's and St Thomas' NHS Foundation Trust.
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2. Coull A, Lovett J, Rothwell P, on behalf of the 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: 326-8.
3. Paul NLM, Simoni M, Rothwell PM, for the Oxford Vascular Study. Transient isolated brainstem symptoms preceding posterior circulation stroke: a population-based study. Lancet Neurol 2013; 12: 65-71.
4. NICE. Stroke: diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). CG68. London, NICE, July 2008.
5. Rothwell PM, Giles MF, Chandratheva A et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet 2007; 370: 1432-42.
6. Stephen M, Davis M, Geoffrey A et al. Secondary prevention after ischaemic stroke or transient ischaemic attack. N Engl J Med 2012; 366: 1914-22.
7. Wang Y, Wang Y, Zhao X et al. Clopidogrel with aspirin in acute minor stroke or transient ischaemic attack. N Engl J Med 2013; 369: 11-19.
8. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033-41.
9. NICE. Clinical management of primary hypertension in adults. CG127. London, NICE, August 2011.
10. Amarenco P, Bogousslavsky J, Callahan A III et al. High-dose atorvastatin after stroke or TIA. N Engl J Med 2006; 355: 549-59.
11. Rothwell PM, Eliasziw M, Gutnikov SA et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004; 363: 915-24.
12. NICE. Atrial fibrillation: the management of atrial fibrillation. CG180. London, NICE, June 2014.
13. Pendlebury ST, Rothwell PM. Risk of recurrent stroke, other vascular events and dementia after transient ischaemic attack and stroke. Cerebrovasc Dis 2009; 27 Suppl 3: 1-11.