Clinical Review: Stroke - epidemiology, diagnosis and management

Section 1: Epidemiology and aetiology

Every year, 174-216 people per 100,000 have a stroke in the UK.¹ That is one every five minutes.

Stroke causes 11% of all deaths and every year, more women die of stroke than of breast cancer.

There are about 900,000 survivors living with stroke, about half of whom are disabled.

Worldwide, in 2010 there were 16.9m people with first-ever stroke, 33m stroke survivors, 5.9m deaths and 102m disability adjusted life years lost due to stroke.¹

Definition

The definition of stroke includes infarction 85%, primary haemorrhage 10% and subarachnoid haemorrhage 5%. Subarachnoid haemorrhage is distinct, so this review concerns only strokes caused by infarction or primary intracerebral haemorrhage.

Stroke shares risk factors with cardiovascular disease. BP is the most important factor in terms of attributable risk, but smoking, obesity and hyperlipidaemia are also important. In older patients, AF remains a significant and undertreated risk factor.

The symptoms of TIA are similar to those of stroke, but by definition, resolve within 24 hours. In practice, patients whose symptoms last for more than an hour very rarely make a complete recovery.

Modern treatments are critically time-dependent, so it is inappropriate to wait before treating, even in patients who present with apparently mild symptoms.

A rule of thumb adopted by the Royal College of Physicians (RCP) is to treat as stroke patients all those whose symptoms have not completely resolved by the time they seek medical attention.

Section 2: Making the diagnosis

Recognising stroke is very difficult in the acute phase, but essential if patients are to access emergency treatment within the shortest possible time.

FAST (Face, Arms, Speech, Time) is useful as a first assessment test before arrival at the hospital. Approximately 80% of 'FAST positive' patients will have a confirmed diagnosis of stroke.^2,3 Conditions that mimic stroke and can lead to a positive FAST test without being a stroke are seizures, sepsis, metabolic disorders, functional presentations and demyelinating conditions.^4,5

Signs of stroke

The cardinal features of the clinical presentation of stroke/TIA are:

• Localism, where there is evidence of localised neurological dysfunction, such as hemiparesis
• Suddenness, where symptoms are worst at onset
• Negativity, characterised by loss of function or sensation rather than increased activity, paraesthesiae or pain

Examples of focal neurological symptoms common in stroke are hemiparesis, dysphasia, ataxia, diplopia or visual field loss.

Less focal symptoms and signs include vertigo, amnesia, lightheadedness, loss of consciousness and confusion. These are more likely to be related to another condition, rather than stroke/TIA.^5,6

TIA and stroke are different presentations of the same entity. However, patients who have a TIA also risk a stroke in the near future. In these cases, rapid diagnosis, starting treatment and addressing risk factors of stroke should be considered an emergency.

Patients with TIA can be divided into risk categories using the ABCD2 score (table 1). Those with a score of ≥4 would be high risk.⁷

However, patients with more than one episode within a week, or those in AF or on anticoagulation are high-risk TIA, regardless of their score.^7,8

Investigations

CT is the primary imaging modality. Haemorrhage is visible and modern CT scanning can confirm the diagnosis in about 80% of cases of infarction in patients scanned within six hours of onset.

MRI is much more sensitive and specific, but takes longer and can be difficult in acutely unwell patients. Availability of MRI in the emergency situation is limited at present.

Perfusion imaging, using CT or MRI, can be used to identify areas of reversible brain ischaemia as targets for treatment.

CT-MR angiography of the intracranial and extracranial vessels is increasingly useful to identify internal carotid artery stenosis and dissection, as well as intracranial arteriovenous malformations and aneurysms.

Doppler imaging of the internal carotid arteries is useful in screening for stenosis, and echocardiography and 24-hour ECG are used to identify cardiac sources of embolism.

Routine blood tests, including lipid profile, help with identification of treatable risk factors, as well as rare causes of stroke.^8-10

Section 3: Managing the condition

TIA patients in sinus rhythm should start antiplatelet therapy (aspirin or clopidogrel) immediately, without waiting for further assessments. High-risk patients should receive specialist assessment within 24 hours of onset and low-risk patients, within seven days.⁸

The most cost-effective treatment for acute stroke is prompt admission to a stroke unit, a geographically defined unit with an expert multidisciplinary team.

Maintenance of normal physiology, prevention and early treatment of complications, such as nosocomial infection or neurological deterioration, and early mobilisation all contribute to the demonstrated reductions in mortality and disability. Stroke units reduce costs and save lives.^11,12

Thrombolysis

Some patients with ischaemic stroke are candidates for thrombolysis with alteplase.

In spite of a significant bleeding risk, thrombolysis leads to an overall reduction in disability if used within the first 4.5 hours. It is worth considering up to six hours after stroke onset, as there is a reduction in disability, although there is possibly an increased mortality risk.

The most notable benefits are seen if treatment is possible much earlier. One in three patients treated within 90 minutes will make a full functional recovery, as will one in six of those treated within three hours.^12,13

For most patients with ischaemic stroke, early treatment with aspirin is indicated. This prevents recurrence in ischaemic stroke and probably promotes vascular recanalisation. Routine use of low molecular weight heparin and stockings is not effective in preventing DVT in stroke, although intermittent pneumatic compression is.^14,15

About 40% of stroke survivors are considered suitable for early supported discharge (ESD).

For this group, ESD is associated with better functional outcome, lower hospital readmission rates and increased patient satisfaction compared with the alternative of inpatient rehabilitation.

Newer therapies under development include alternative thrombolytic agents, intra-arterial therapies to promote recanalisation, prothrombotic agents in haemorrhagic stroke, and levodopa and SSRIs in rehabilitation.

Patients diagnosed with stroke and TIA should be advised not to drive for one month. Disabled survivors at one month should inform the Driver and Vehicle Licensing Agency and may require assessment before being allowed to drive.

Section 4: Prognosis

Approximately 30% of patients will have a recurrent stroke within five years. Risks can be substantially reduced by lifestyle modification and medical treatment.

BP lowering should focus on a target <130/80mmHg.

Antithrombotic treatment with clopidogrel 75mg once daily is the first-line treatment for patients with ischaemic stroke in sinus rhythm. Lipid lowering with statins should be initiated unless contraindicated.^8,16

Risk of AF

AF is associated with a high risk of recurrent stroke. In almost all stroke survivors with AF, the risk of stroke without anticoagulation is higher than the risk of significant bleeding on anticoagulant therapy.

For example, the risk of intracranial haemorrhage resulting from falls while taking anticoagulants is more than 100 times lower than the stroke risk in untreated AF.

The bleeding risk of antiplatelet therapy is similar.

The RCP guidelines recommend anticoagulant therapy after ischaemic stroke in the presence of AF. If bleeding risk on anticoagulant therapy is deemed too high, antiplatelets should be avoided. However, anticoagulation is underprescribed in this high-risk group.¹⁷

Section 5: Case study

Alice, a 68-year-old retired GP who enjoys swimming, jogging and golf, presented with left-sided paralysis of the arm and leg, slurred speech and inability to walk. She had been diagnosed with hypertension in the past, for which she was on medication.

When she arrived at the hospital, Alice's symptoms had been present for eight hours. A CT brain scan showed ischaemic changes on the right hemisphere. She was admitted to the stroke unit and started aspirin therapy immediately.

Within 24 hours, Alice was assessed by the physiotherapist, occupational therapist and speech and language therapist. Initially, she needed assistance with most activities of daily living. She was discharged on the fifth day for rehabilitation at home. At six-week review, she was taking clopidogrel, simvastatin and her antihypertensives. She was also back to playing golf.

Section 6: Evidence base

Clinical trials

• IST-3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6h of acute ischaemic stroke (the third international stroke trial (IST-3)): a randomised controlled trial.Lancet 2012; 379: 2352-63.

• IST-3 shows that thrombolysis given up to six hours from onset decreases disability at six months. Treating elderly patients (>80 years) seems as effective as treating younger ones.

• CLOTS Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013; 382: 516-24.

CLOTS has shown the benefit of intermittent pneumatic compression, with an absolute risk reduction of proximal DVT of 3.6%.

Guidelines

• Royal College of Physicians. National clinical guideline for stroke (fourth edition). 2012. http://www.rcplondon.ac.uk/resources/stroke-guidelines

• NICE. Stroke. Diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). CG68. London, NICE, July 2008. http://www.nice.org.uk/cg68

• NICE. Stroke quality standard. London, NICE, June 2010. http://guidance.nice.org.uk/QS2

Resources

• British Association of Stroke Physicians www.basp.ac.uk

• Stroke Association. www.stroke.org.uk

• Stroke and driving www.gov.uk/stroke-and-driving

Click here to take a test on this article and claim a certificate on MIMS Learning

References
1. Feigin VL, Forouzanfar MH, Krishnamurthi R et al. Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010.
Lancet 2014; 383(9913): 245--55.
2. Harbison J, Hossain O, Jenkinson D et al. Diagnostic accuracy of stroke referrals from primary care, emergency room physicians, and ambulance staff using the face arm speech test. Stroke 2003; 34: 71-6.
3. Nor AM, McAllister C, Louw SJ et al. Agreement between ambulance paramedic- and physician-recorded neurological signs with Face Arm Speech Test (FAST) in acute stroke patients. Stroke 2004; 35: 1355-9.
4. Sarikaya H, Yilmaz M, Luft AR et al. Different pattern of clinical deficits in stroke mimics treated with intravenous thrombolysis. Eur Neurol 2012; 68(6): 344-9.  
5. Nadarajan V, Perry RJ, Johnson J et al. Transient ischaemic attacks: mimics and chameleons. Pract Neurol 2014; 14: 23-31.
6. Nor AM, Davis J, Sen B et al. The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument. Lancet Neurol 2005; 4(11): 727-34.
7. Johnston SC, Rothwell PM, Nguyen-Huynh MN et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007; 369: 283-92.
8. NICE. Stroke. Diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). CG68. London, NICE, July 2008. http://www.nice.org.uk/cg68
9. Saur D, Kucinski T, Grzyska U et al. Sensitivity and interrater agreement of CT and diffusion-weighted MR imaging in hyperacute stroke. Am J Neuroradiol 2003; 24: 878-85.
10. Von Kummer R, Nolte PN, Schnittger H et al. Detectability of cerebral hemisphere ischaemic infarcts by CT within 6h of stroke. Neuroradiol 1996; 38: 31-3.
11. Langhorne P, Williams BO, Gilchrist W et al. Do stroke units save lives? Lancet 1993; 14(342): 395-8.
12. Langhorne P, Fearon P, Ronning OM et al. Stroke unit care benefits patients with intracerebral hemorrhage: systematic review and meta-analysis. Stroke 2013; 44(11): 3044-9.
13. Lees KR, Bluhmki E, von Kummer R et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375(9727): 1695-703.
14. International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet 1997; 349(9065): 1569-81.
15. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013; 382: 516-24.
16. Burn J, Dennis M, Bamford J et al. Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke 1994; 25(2): 333-7.
17. Abdul-Rahim AH, Wong J, McAlpine C et al. Associations with anticoagulation: a cross-sectional registry-based analysis of stroke survivors with atrial fibrillation. Heart 2014; doi:10.1136/heartjnl-2013-305267

• Contributed by Dr Roser Icart-Palau and Dr Patrick Gompertz, consultant physicians at Bart's Health NHS Trust, London.