Stroke: management and prevention - Medicine

STROKE

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Stroke: management and prevention

• The risk of recurrent stroke after TIA or minor stroke is higher than previously thought • The MATCH trial has shown no additional benefit with clopidogrel and aspirin over clopidogrel alone in prevention of recurrent stroke or vascular events

Sarah T Pendlebury Peter M Rothwell

• The efficacy of carotid surgery for secondary prevention of stroke in patients with symptomatic carotid stenosis is highly dependent on the timing of surgery There are various clinical and pathological subtypes of stroke (see page 57), and identification of the subtype is necessary for correct management. whereas one acute infarct with several old infarcts may be more suggestive of a thromboembolic event. • Perfusion-weighted imaging measures the relative rate of blood flow through the brain. It has been proposed that tissue in which ‘perfusion–diffusion mismatch’ (Figure 2) is present (i.e. perfusion is reduced but diffusion-weighted signal change has not yet occurred) represents the ‘ischaemic penumbra’, and thus tissue that may be salvaged if perfusion can be restored quickly. This may be helpful in identifying patients who would benefit from thrombolysis.

Investigations Imaging Brain imaging should be performed within the first 48 hours of the onset of stroke (see below), to determine whether the stroke is haemorrhagic or ischaemic and to exclude other causes (e.g. tumour). Imaging may also establish the site and size of the lesion (e.g. posterior or anterior circulation, lacunar or cortical infarction). CT T shows haemorrhage (as hyperintensity) almost as soon as it occurs. Ischaemic change (sulcal effacement and swelling) may occur as early as 2–3 hours, and by 24–48 hours an ill-defined hypodense area appears. However, CT reveals a clinically appropriate lesion in only about 50% of cases of ischaemic stroke, because of the relatively coarse spatial resolution of CT and poor imaging of the posterior fossa. Occasionally, the occluded artery (particularly the middle cerebral artery trunk) appears hyperdense. MRII – conventional MRI sequences may not show haemorrhage in the first few hours after stroke. In cases of infarction, a T2-weighted hyperintense area may be seen within 6 hours and is present in 90% of patients at 24 hours. The infarcted area may increase in size on later scans. MRI appears to have greater sensitivity than CT for lacunar and posterior circulation infarcts, but scans may be normal even in cases of definite stroke. New developments in MRI include imaging of the extracranial and intracranial vessels (magnetic resonance angiography, MRA), diffusion-weighted imaging and perfusion-weighted imaging. • Diffusion-weighted imaging depends on diffusion of water to generate contrast. It shows changes within minutes of stroke onset (Figure 1) and is therefore useful in hyperacute stroke and in distinguishing acute from chronic infarction. The presence of bilateral multiple acute infarcts may suggest cardioembolism,

Imaging of the extracranial and cerebral vessels: imaging of the carotid arteries should be undertaken in all patients with transient ischaemic attacks (TIAs) or mild-to-moderate ischaemic stroke in the anterior circulation, because surgical treatment of recent symptomatic carotid stenosis reduces the risk of recurrent stroke (see below). Carotid ultrasonography is the most commonly used method. MRI, CT and conventional angiography (Figure 3) enable visualization of all of the cerebral vessels, whereas ultrasonography (usually) and CT angiography look only at the carotid bifurcation. All non-invasive methods are subject to error (MRA tends to overestimate and CT angiography to underestimate stenosis), and tight stenoses may be misidentified as occlusions. Other investigations Blood tests that should be performed are shown in Figure 4. Urinalysis may reveal abnormalities in patients with diabetes, vasculitis or infective endocarditis. A drug screen (amfetamines, cocaine, Ecstasy) should be considered in young patients with stroke of no obvious cause. Cardiac investigations: ECG abnormalities such as prolongation of the QT interval, ST-segment depression or elevation, paroxysmal supraventricular tachycardia and atrial fibrillation may precede or follow stroke (particularly haemorrhage) and should prompt consideration of cardiac monitoring. Echocardiography should be performed in all patients with suspected cardioembolic stroke.

Sarah T Pendlebury y is Specialist Registrar in General (Internal) Medicine and Geratology at John Radcliffe Hospital and the Radcliffe Infirmary, Oxford, UK. Her research interests include recovery mechanisms after stroke.

Genetic testing is undertaken in patients with an inherited disorder such as MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) or CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy).

Peter M Rothwelll is Professor of Clinical Neurology and Director of the Stroke Prevention Research Unit at the University of Oxford, UK. He trained in Edinburgh and Oxford and at the University of Western Ontario, London, Canada, and was an MRC senior clinical fellow in Oxford.

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© 2004 The Medicine Publishing Company Ltd

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1 Examples of the use of diffusion-weighted imaging in acute stroke. a A patient with symptomatic carotid stenosis with several acute infarcts in th he middle cerebral artery territory. b A middle-aged wom man with a long history of anxiety-related medical problem ms who was complaining of transient numbness over the right side of the body 24 hours previously. The arrow shows an n acute left thalamic infarct.

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coexistent hypertensive encephalopathy, aortic dissection, acute myocardial infarction or severe left ventricular failure.

General management of acute stroke Interventions in acute stroke should aim to minimize mortality and disability and to prevent complications such as deep vein thrombosis (DVT).

Oxygenation: hypoxia exacerbates cerebral ischaemia. There are no data supporting routine administration of supplementary oxygen, but oxygen should be given if hypoxia is detected (oxygen saturation < 92%). Patients should be nursed sitting up or in a chair when possible, to improve pulmonary ventilation.

Admission to a stroke unit: ideally, all patients with stroke should be admitted to a specialist stroke unit. There is convincing evidence that such units reduce mortality, morbidity and dependency.1 For every 100 patients managed in a stroke unit, three deaths are prevented, three patients avoid long-term nursing home care and an extra six patients return home, compared with conventional care in a general medical ward. The evidence for mobile stroke teams is less convincing. Organized stroke-unit care is effective regardless of the patient’s age and sex, the severity of stroke symptoms on admission and stroke pathology or subtype. Patients with moderate-to-severe stroke appear to benefit most.

Control of blood glucose: hyperglycaemia in acute stroke may be associated with neurological deterioration and poor outcome in the short term. Blood sugar should be maintained within normal limits, with intravenous insulin if necessary. Pyrexia: fever may be secondary to infection, but may also occur in patients with severe cerebral lesions. Observational data suggest that pyrexia increases infarct size. Infection should be treated promptly, but there is no evidence supporting routine use of antipyretics such as paracetamol in patients with temperatures above 37.5ºC (though they are widely used in practice). Pilot studies have suggested some benefit of induced hypothermia in severe middle cerebral artery territory infarction.

Blood pressure: optimal management of blood pressure in acute stroke is uncertain. Blood pressure is often elevated on admission, but tends to decrease spontaneously during the first few days. Existing antihypertensive therapy should be continued. Treatment may be considered in those with a sustained blood pressure of more than 220/120 mm Hg in cerebral infarction or more than 185/105 mm Hg in cerebral haemorrhage. Cerebral autoregulation is disturbed after stroke, so lower levels of hypertension should probably not be treated in the acute phase, except in patients with

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Fluid balance, swallowing and nutrition: intravenous fluid replacement should be used to correct dehydration. Patients who can swallow satisfactorily should be placed in a sitting position to eat or drink. Patients with abnormal swallow should be assessed

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2 Magnetic resonance angiography (a), diffusion-weighted imaging (b) and perfusion-weighted imaging (c) performed in a patient 2.5 hours after onset of aphasia and right hemiparesis. Occlusion of the left middle cerebral artery trunk (arrow) is seen, with a small diffusion abnormality and a large perfusion abnormality indicative of a large ischaemic penumbra (tissue potentially salvageable with thrombolysis).

by a speech and language therapist. Nasogastric or percutaneous endoscopic gastrostomy tube-feeding should be instituted when oral intake is not possible or is insufficient. Malnutrition is common after acute stroke and may be a risk factor for a poor outcome. Advice from a dietitian should be sought for patients needing nutritional support.

contractures, pressure ulcer, depression, constipation, urinary tract infection and falls. Rehabilitation should focus on minimizing further physical deterioration, restoring function, developing strategies for coping with impairment and preventing secondary conditions, and should extend to preparing patients for independent life in the community.

Early mobilization and rehabilitation: early mobilization may reduce the incidence of complications such as pneumonia, DVT, pulmonary embolism, orthostatic reactions, painful shoulders,

DVT prophylaxis: patients without cerebral haemorrhage should receive aspirin, and dehydration should be avoided in all patients. Compression stockings should be used in immobile patients, though there are no randomized trial data.

Specific treatment of acute stroke Acute ischaemic stroke Thrombolysis is likely to be beneficial in patients with major ischaemic stroke with a large ischaemic penumbra (Figure 2), but is likely to be ineffective or harmful in completed infarction and when the ischaemic penumbra is small. How to identify patients who would benefit from thrombolysis is currently unclear. • In a randomized controlled trial of recombinant tissue plasminogen activator (rt-PA) given within 3 hours, thrombolysis significantly improved outcome despite an increased risk of cerebral haemorrhage.2 The improved outcome in the thrombolysis group was maintained at 1 year. • Systematic reviews of intravenous thrombolytic therapy suggest benefit from thrombolysis within the first 6 hours of stroke, with a significant reduction in combined death or dependency at the end of follow-up despite an increase in the number of intracranial haemorrhages and deaths. Patients treated within 3 hours exhibited improved outcome with no excess deaths. • A recent re-analysis of individual patient data from the NINDS, ECASS I and II, and ATLANTIS trials (99% of patients randomized in trials of rt-PA in stroke) has confirmed that the benefit from thrombolysis decreases with time since stroke onset (Figure 5).3 It is most beneficial if given within 90 minutes.

3 Carotid angiogram showing a severe carotid stenosis before and after treatment with angioplasty and stent insertion.

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There are few data on the use of combination antiplatelet agents and how to deal with patients who suffer a stroke on aspirin, but trials are ongoing (see below). Heparins and heparinoids – immediate therapy with systemic anticoagulants (including unfractionated heparin, low molecular weight heparin, heparinoids and specific thrombin inhibitors) in patients with acute ischaemic stroke is not associated with benefit. These agents reduce the risk of DVT and pulmonary embolus, but are associated with a significant and dose-dependent risk of intracranial haemorrhage. There is little evidence to guide the treatment of specific causes of ischaemic stroke such as dissection and basilar artery thrombosis – conditions that are associated with progressive symptoms. Oral anticoagulants – patients in atrial fibrillation after presumed ischaemic stroke or TIA should be anticoagulated to prevent further stroke. The best time to start therapy after ischaemic stroke is unclear, however, because the risk of haemorrhagic transformation is difficult to predict. Current guidelines suggest that patients should be treated with aspirin for the first 2 weeks before anticoagulation is introduced. Other therapies – there is insufficient evidence to support the use of fibrinogen-depleting agents, corticosteroids and haemodilution in acute ischaemic stroke. Neuroprotective agents have attracted interest, but results have been disappointing.

Blood tests in the investigation of stroke First line • Full blood count • ESR • Urea and electrolytes • Cholesterol • Glucose • Inflammatory markers • Clotting screen • Platelets • Thyroid function (for atrial fibrillation)

Second line • Thrombophilia screen, • Blood cultures (infective endocarditis) • Antiphospholipid antibody • Autoantibody screen • Homocysteine • Lactate (MELAS) • Cardiac enzymes/troponin • Calcium (hypercalcaemia or hypocalcaemia may rarely cause focal deficit)

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Current guidelines regarding thrombolysis vary, but there is agreement that it should be administered only by a physician with expertise in stroke and should be avoided more than 3 hours after stroke onset except as part of a randomized trial. Intra-arterial thrombolysis enables treatment of vessel occlusion and may allow safer treatment of patients at increased risk of haemorrhagic complications. One randomized trial showed benefit in proximal middle cerebral artery occlusion. There are no trials in the posterior circulation (e.g. basilar artery occlusion) or direct comparisons between intra-arterial and intravenous thrombolysis. Antiplatelet therapy – aspirin started within 48 hours of acute ischaemic stroke onset reduces mortality and recurrent stroke, so early brain imaging to exclude haemorrhage is important. Patients intolerant of aspirin should be treated with clopidogrel or dipyridamole. There is no clear evidence favouring any particular dose of aspirin, but lower doses are preferred because toxicity is dose-related. Current guidelines suggest 150–300 mg daily initially, followed by long-term treatment with 75–150 mg daily.

Acute intracranial haemorrhage Coagulation defects in patients with intracerebral haemorrhage should be corrected urgently. Surgical evacuation of medium-sized intracerebral haematomas was not shown to be beneficial in the recent STICH trial. Patients with cerebellar stroke (particularly those with acute hydrocephalus from compression of the aqueduct) should be referred urgently to a neurosurgeon for possible ventricular shunting and decompression surgery.

Primary prevention Atherothromboembolism: primary prevention of atheroma involves avoidance and/or treatment of modifiable risk factors including hypertension, smoking, diabetes and hypercholesterolaemia. Current evidence suggests only modest benefit from surgery for asymptomatic carotid stenosis, because of the low risk of stroke on medical treatment.

Patients treated with recombinant tissue plasminogen activator: early treatment improves outcome compared with controls3

Small vessel disease: at present, the risk factors for the development of small vessel disease are insufficiently characterized. Current practice should follow preventive measures as outlined for large vessel disease (atheroma).

Adjusted odds ratio

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Atrial fibrillation: the presence of non-rheumatic atrial fibrillation (see MEDICINE 30:6, 140) increases the risk of stroke fivefold. The risk increases with age and with the presence of factors such as previous hypertension, heart failure/impaired left ventricular function, thyroid disease, valve disease and diabetes. • In high-risk patients (8–12% annual stroke risk – age > 75 years and clinical risk factors such as diabetes or hypertension), use of warfarin to a target INR of 2–3 is recommended. • Low-risk patients (1% annual stroke risk – age < 65 years and no other risk factors) and those in whom warfarin is contraindicated can be managed with aspirin.

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Stroke onset to treatment r time (minutes) Based on a pooled analysis of 2776 patients from randomized controlled trials

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• In moderate-risk patients, warfarin or aspirin should be given on an individual basis.

Benefit of carotid endarterectomy in symptomatic patients with 70% carotid stenosis Propor r tion of patients with an event

Primary intracerebral haemorrhage: the major risk factor for this is hypertension, and the risk is reduced by lowering blood pressure.

Secondary prevention General principles Lifestyle changes: many stroke patients benefit from lifestyle changes including cessation of smoking, weight reduction and modification of excess alcohol intake.

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Blood pressure lowering: the PROGRESS trial showed that blood pressure reduction (using perindopril and indapamide) after haemorrhagic or ischaemic stroke reduces the risk of subsequent stroke even in patients with ‘normal’ blood pressure.4 However, blood pressure should not be reduced aggressively in those with bilateral severe carotid stenosis, and possibly in severe basilar or bilateral vertebral artery disease, because this may increase the risk of stroke by compromising cerebral blood flow.

Graph shows cumulative risk of ipsilateral ischaemic stroke and operative stroke or death 5-year absolute risk k reduction = 16.0% (11.2–20.8)

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aetiology (but those with cardioembolic sources or > 50% carotid stenosis were excluded), showed no additional benefit with warfarin at a mean INR of 1.8 (target INR 1.4–2.8). • Treatment with warfarin to a target INR of 3–4.5 (SPIRIT trial) has been shown to be associated with significant harm caused by an increase in major bleeding complications, particularly intracerebral haemorrhage. • An ongoing trial (ESPRIT) is comparing aspirin, aspirin and extended-release dipyridamole, and warfarin (INR 2–3). Patients who have suffered a stroke and are in atrial fibrillation are at high risk and should be anticoagulated if there are no contraindications. Because of the lack of randomized evidence, patients with presumed cardioembolic stroke secondary to other causes should receive antithrombotic therapy on an individual basis. No significant difference between anticoagulants and aspirin was found in a recent study of stroke secondary to patent foramen ovale.

Cholesterol lowering: the Heart Protection Study showed that treatment with simvastatin, 40 mg, reduces the risk of stroke and other vascular events in high-risk patients (previous ischaemic stroke, coronary or peripheral vascular disease or diabetes).5 This was the case even in patients with ‘normal’ cholesterol levels (low-density lipoprotein cholesterol < 3.5 mmol/litre). In the subgroup of patients with pre-existing cerebrovascular disease, treatment with simvastatin reduced major vascular events by 20% over the 5-year treatment period. Notably, there was no increased risk of haemorrhagic stroke, contradicting previous suggestions that cholesterol reduction is associated with such a risk. Because patients with primary intracerebral haemorrhage are at high risk of further thrombotic vascular events, it could be argued that they should also receive statins. Ischaemic stroke Antiplatelet agents reduce the risk of recurrent stroke and vascular death; treatment of 1000 patients for 3 years after stroke results in 36 fewer serious vascular events and 15 fewer deaths per 1000 patients. Most trial data concern aspirin, but newer antiplatelet agents such as clopidigrel and extended-release dipyridamole are also effective. However, it is uncertain whether they provide sufficient additional benefit over aspirin to justify the extra cost. There is interest in combination antiplatelet therapy, particularly in patients perceived to be at high risk of recurrent ischaemic events. The ESPS 2 trial showed a relative risk reduction for stroke of 30% (9.5% vs 12.5%) with aspirin and dypiridamole vs aspirin alone in patients with prior TIA or ischaemic stroke. The recent MATCH trial of clopidogrel and aspirin vs clopidogrel alone showed no additional benefit with the combination therapy. There are several other ongoing trials of combination therapy.

Benefit of endarterectomy declines rapidly with time6 70–99% stenosis 50–69% stenosis

Absolute risk k reduction (%) (95% CI)

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Anticoagulation has been considered for secondary prevention of stroke in patients in sinus rhythm. • A recent trial of aspirin vs warfarin in patients in sinus rhythm (WARSS), in which subjects were not selected according to stroke

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Carotid endarterectomy plus best medical treatment Best medical treatment alone

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Patients with moderate stenosis (50–69%) benefit from surgery r if it is performed early.

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Surgical/endovascular treatments: significant atherosclerotic narrowing at or around the origin of the ipsilateral internal carotid artery is found in about 20–30% of patients with TIAs or ischaemic stroke. Combined data from the three major randomized trials of endarterectomy for symptomatic carotid stenosis showed that surgery was highly beneficial in those with a stenosis of 70% or more and moderately beneficial for 50–69% stenosis (Figure 6).

However, there was no clear benefit in patients with the most severe disease (near-occlusion). Operative mortality was 1.1% and the operative risk of stroke and death was 7.0%. Several other clinical and angiographic characteristics influence the efficacy of surgery, particularly the timing (Figure 7).6 With the recent suggestion that the risk of early recurrent stroke is very high in large artery-associated stroke (see below), and evidence from endarterectomy trials that the benefit of surgery is greatest in the first few weeks after stroke, early surgery is becoming more common. Early carotid surgery (< 3–6 weeks after symptom onset) appears not to carry an increased risk of complications compared with surgery performed later, in patients who are clinically stable. Carotid angioplasty is currently being evaluated as an alternative to endarterectomy. Current evidence from the CAVATAS investigators suggests that angioplasty with or without stenting is associated with a procedural risk similar to that of endarterectomy, but a higher rate of re-stenosis during follow-up. However, improvements in cerebral protection devices may reduce the procedural risks, and several randomized trials of angioplasty and stenting with cerebral protection vs endarterectomy are ongoing. Randomized controlled trials have not been performed in surgery or angioplasty for posterior circulation disease or intracranial disease. Such procedures are occasionally undertaken in patients whose symptoms persist despite antithrombotic therapy.

Percentage of patients who were dead or dependent at 6 months in the Oxford Community Stroke Project, a population-based study of first strokes7 Cerebral infarction r All Cerebral infarction Primary intracerebral haemorrhage Subtypes of ischaemic stroke All Total anterior circulation infarct Partial anterior circulation infarct

Primary intracerebral haemorrhage: the PROGRESS trial included patients with primary intracerebral haemorrhage, and blood pressure lowering was seen to be beneficial (see above) in the prevention of recurrent stroke. In view of the increased vascular risk, such patients should probably also receive statins. Long-term treatment with aspirin is advocated by some authorities, to reduce the overall vascular risk. However, it is currently unclear how to predict those at high risk of recurrent hameorrhage and thereby determine the risk:benefit ratio in individual patients.

Lacunar infarct f Posterior circulation infarct f Dead

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High early risk of recurrent stroke (8–12% within the first week)8 in a population-based study 25

Events/number Events/number Odds of patients (%) of patients (%) ratio

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Recurrent stroke is more likely aft f er large arteryy stroke than after a cardioembolic or lacunar event

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Large arteryy inffarct vs small vessel infar f ct OXVASC V 4/18 (22.2) 1/18 (5.6) OCSP 5/78 (6.4) 1/119 (0.8) Erlangen 2/71 (2.8) 0/120 (0.1) Rochester 9/70 (12.9) 1/72 (1.4) Subtotal 20/237 (8.4) 3/329 (0.9)

4.86 8.08 34.75 10.48 8.68

0.5–48.6 0.9–70.6 20.0–56.6 1.3–85.0 2.6–29.1

Large arteryy inffarct vs cardioembolic stroke OXVASC V 4/18 (22.2) 1/28 (3.6) OCSP 5/78 (6.4) 3/127 (2.4) Erlangen 2/71 (2.8) 5/143 (3.5) Rochester 9/70 (12.9) 6/132 (4.5) Subtotal 20/237 (8.4) 15/430 (3.5)

7.71 2.83 0.80 3.10 2.56

0.8–75.8 0.7–12.2 0.2–4.2 1.1–9.1 1.3–5.1

1-month recurrent stroke risk k from four different population-based studies

p(sig) < 0.001 p(het) = 0.926

p(sig) < 0.01 p(het) = 0.361 0.1

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Odds ratio (95% Cl) l

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Prognosis

REFERENCES 1 Stroke Unit Trialists’ Collaboration 1997. Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. BMJJ 1997; 314: 1151–9. 2 National Institute of Neurological Disorders and Stroke rtPA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med d 1995; 333: 1581–7. 3 ATLANTIS, ECASS, and NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancett 2004; 363: 768–74. 4 PROGRESS Collaborative Group. Randomised trial of a perindoprilbased blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancett 2001; 358: 1033–41. 5 Heart Protection Study Collaborative Group. Effects of cholesterol lowering with simvastatin on stroke and other major vascular events in 20 536 people with cerebrovascular disease or other high risk conditions. Lancett 2004, 363: 757–67. 6 Rothwell P M, Eliasziw M, Gutnikov S A et al. Effect of endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and to the timing of surgery. Lancett 2004; 363: 915–24. 7 Bamford J, Sandercock P, Dennis M et al. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991, 337: 1521–6. 8 Coull A, Lovett J K, Rothwell P M. Early risk of stroke after a TIA or minor stroke in a population-based incidence study. BMJJ 2004; 328: 326–8.

Patients who have suffered a stroke are at high risk of vascular death. Heart disease (40%) is the most common cause of death after the immediate post-stroke period, followed by further stroke (25%) and other vascular causes (5%). The most common vascular event in the first year is recurrent stroke. Recovery: about 10% of patients die within 30 days of stroke – onehalf from immobility-related causes and one-quarter from direct neurological sequelae. Of those who survive, about 50% remain disabled after 6 months and one-third are functionally dependent at 1 year. Most stroke patients experience some degree of recovery. Various mechanisms have been postulated, including restoration of blood supply, resolution of oedema, and neuroplasticity in which intact areas of the brain take over the functions of neighbouring damaged areas. Adaptive changes are also important, particularly in the later phases of recovery, when patients learn means of overcoming their impairments. The extent of recovery is difficult to predict for individual patients, particularly immediately after stroke. Improvement is most rapid in the first few days and weeks, but may continue more slowly for 1–2 years. Data from the Oxford Community Stroke Project suggest that patients with lacunar infarcts or posterior circulation infarcts have a better prognosis as a group than those with total anterior circulation infarcts or primary intracerebral haemorrhage (Figure 8).7 However, some patients with relatively small-volume lacunar infarcts remain severely handicapped if the infarct is located in an area containing densely packed fibres (e.g. pyramidal tract). In individual patients, measures of clinical severity at stroke onset (closely correlated with volume of brain lesion) are at least as useful as more sophisticated methods in predicting outcome.

FURTHER READING Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJJ 2002; 321: 71–86. Warlow C P, Dennis M S, van Gijn J et al. Stroke: a practical guide to management. 2nd ed. Oxford: Blackwell Science, 2001.

Risk of recurrent stroke: it has recently become clear that the early risk of recurrent stroke after TIA or minor stroke is higher than previously thought (Figure 9a):8 • 7-day risk is 8–12% • 1-month risk is 18%. Consequently, assessment of patients with TIA must be rapid and comprehensive. The risk appears to be highest in those with large artery-associated stroke (atherothromboembolism), followed by cardioembolic strokes (Figure 9b). Lacunar strokes have a lower risk of recurrence. In patients with carotid atheroma, the risk of stroke is strongly related to the severity of ipsilateral extracranial carotid stenosis, and to whether the stenosis is symptomatic (15%, 5% and 2% in successive years after the index event) or asymptomatic (2% per year). In those on medical treatment, the annual risk of stroke from symptomatic stenosis involving the intracranial carotid or the middle cerebral artery is about 7–10%. Extracranial vertebral artery stenosis is thought to be relatively benign, but basilar stenosis is associated with a higher risk of stroke. In patients with primary intracerebral haemorrhage, available data suggest an annual risk of recurrent stroke of about 7% (25% haemorrhagic). The risk is increased in those with an underlying cause (e.g. arteriovenous malformation, cerebral amyloid angiopathy, poorly controlled hypertension).

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Practice points • Heart disease is the most common cause of death after the first 30 days in patients who have suffered an ischaemic stroke • All patients admitted to hospital with stroke should be managed on a stroke unit, because such units reduce death and dependency • Thrombolysis is effective in acute ischaemic stroke if given within 3 hours of stroke onset • Patients with TIA or minor stroke should undergo urgent assessment, because the risk of recurrent ischaemic stroke is highest in the first few days • Atherothromboembolic strokes are most likely to recur early, and in patients with carotid atheroma the risk of recurrence is strongly correlated with the degree of stenosis • Carotid endarterectomy for high-grade symptomatic stenosis prevents recurrent stroke, but the benefit declines with time since stroke

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