Clinical Review: Stroke

By Dr Jonathan Birns, consultant in stroke medicine, geriatrics and general medicine, Guy's and St Thomas' NHS Foundation Trust and honorary senior lecturer, King's College London.

Without brain imaging, such as CT scanning, it is impossible to determine whether a stroke is ischaemic or haemorrhagic (above) (Photograph: Dr Jonathan Birns)
Without brain imaging, such as CT scanning, it is impossible to determine whether a stroke is ischaemic or haemorrhagic (above) (Photograph: Dr Jonathan Birns)

Section 1: Epidemiology and aetiology
Stroke is defined as a rapid onset of focal neurological deficit lasting more than 24 hours, with no apparent cause other than disruption of blood supply to the brain.

A transient ischaemic attack (TIA) refers to a similar presentation that resolves within 24 hours, although the majority of TIAs resolve within one hour.

Stroke is a common condition affecting around 150,000 people every year in the UK and, at any given time, there are about 2,500 stroke patients in an average health district.

Risk factors
While the incidence of stroke increases with age, 25 per cent of all strokes occur in people below the age of 65. Risk factors for stroke include hypertension, diabetes mellitus, dyslipidaemia, cardiac disease, African-Caribbean ethnicity, obesity, smoking and recreational drug and alcohol misuse.

Approximately 15 per cent of strokes are haemorrhagic and the remainder are ischaemic. Ischaemic strokes may be classified in terms of their aetiology of large vessel atherothromboembolism, cardioembolism, small vessel occlusion, or other determined or undetermined causes.

Stroke subtypes
The proportions of the major stroke subtypes depend on ethnicity. In Caucasians, approximately 15 per cent are due to large vessel disease, 30 per cent are due to cardioembolism and 15 per cent are due to small vessel disease.

In African-Caribbean people, approximately 8 per cent are due to large vessel disease, 15 per cent are due to cardioembolism and 30 per cent are due to small vessel disease.

Epidemiological studies have shown the exact aetiopathogenesis of stroke may be unknown in up to 20 per cent of cases and around 5 per cent of strokes are found to be due to a rare or unusual cause.

Less common causes of stroke include arterial dissection, autoimmune or connective tissue disorders, such as systemic lupus erythematosus, and haematological disorders, such as thrombophilic states and sickle cell disease.

Section 2: Making the diagnosis
Clinical features

The symptoms and signs of stroke depend on the brain structures that are affected which are, in turn, dependent on the vascular territory involved.

For example, stroke affecting the anterior cerebral artery territory may result in emotional changes, dysphasia and contralateral weakness.

Stroke affecting the middle cerebral artery territory may result in dysphasia and contralateral weakness, sensory loss, visual field loss and neglect.

Stroke affecting the posterior cerebral artery territory may result in contralateral visual field loss, neglect, weakness and sensory loss.

Strokes affecting the posterior brain structures supplied by the vertebrobasilar arterial system may cause nausea, vomiting, vertigo, visual disturbance, nystagmus, dysarthria, ataxia, weakness or sensory disturbance.

Recognising stroke
Strokes involving only a small blood vessel (<400(mu)m in diameter) supplying deep brain structures lack cortical features (dysphasia, visual field loss, neglect, perceptual abnormalities) and present as pure hemiparesis, hemisensory loss, sensorimotor stroke or ataxic hemiparesis.

A detailed history is crucial to exclude other possible diagnoses. Key features pertain to the symptoms being focal rather than non-focal, negative (something not working) rather than positive, of sudden onset and maximal at onset rather than progressing over a period.

Rapid recognition of stroke is critical to acute care pathways. Structured assessment tools, such as face arm speech test (FAST) and recognition of stroke in the emergency room (ROSIER) tests, have been demonstrated to be effective pre-hospital and in emergency departments respectively.

Clinical evaluation should assess for conscious level, temperature, heart rate and rhythm, BP, cardiac murmurs, carotid bruits and evidence of aspiration, in addition to a detailed neurological examination.

Investigation
Basic blood tests to assess for derangement of serum haematological or biochemical parameters should be undertaken in all suspected stroke patients in addition to brain imaging.

Without brain imaging it is impossible to determine whether a stroke is ischaemic or haemorrhagic. The most commonly used modality of brain imaging in the acute assessment of stroke patients is CT scanning due to its ease of use and availability.

MRI has higher sensitivity to tissue oedema and ischaemia but is less available, more expensive, potentially claustrophobic for patients and contraindicated for patients with fragments of metal, cardiac pacemakers or any other electrical or magnetic implanted device.

Section 3: Managing the condition
Stroke used not to be considered an emergency and hospitalisation was thought to be necessary only for nursing or social care needs.

This nihilistic perception has been changed by evidence demonstrating the effectiveness of acute stroke care and that for every minute a stroke goes untreated, 1.9 million brain neurons die.

Angiogram pretreatment

Angiogram pretreatment showing a clot


Angiograms pretreatment (left, arrow points to clot) and  post-treatment (right)

Stroke unit care
RCTs have demonstrated reductions in mortality, institutionalisation and dependency for patients managed on a stroke unit compared with conventional care, with 19 per cent more patients alive and independent at one year.

A stroke unit is a discrete area within a hospital, staffed by a specialist multidisciplinary team with access to monitoring and rehabilitation equipment.

Stroke unit guidelines advocate interventions to maintain physiological homeostasis in terms of oxygenation, hydration, nutrition and BP and glucose control, in addition to strategies to prevent and treat complications, such as urinary incontinence, pressure sores and venous thrombosis.

IV thrombolysis
In addition to control of classical vascular risk factors, such as hypertension and hyperlipidaemia, certain specific treatment strategies exist.

RCTs have demonstrated that treatment with IV thrombolysis, which breaks down blood clots, improves the outcome of one in three ischaemic stroke patients treated within three hours of symptom onset and of one in six patients treated in the three to 4.5 hour window.

More specifically, trial data has shown that thrombolysis within three hours provides a 14 per cent increase in the chance of being alive and independent three months after stroke and thrombolysis at three to 4.5 hours provides a 7 per cent increase.

Perfusion imaging allows direct visualisation of brain tissue that is potentially salvageable with thrombolysis.

Intra-arterial thrombolysis
Administering thrombolytic agents directly to the area of clot may increase efficacy and reduce the risk of bleeding.

Intra-arterial thrombolysis is recommended as an option for treatment of selected patients who have a major stroke of less than six hours duration due to occlusion of the middle cerebral artery and who are not otherwise candidates for IV thrombolysis.

However, clinical benefit may be counterbalanced by delays initiating treatment as treatment requires the patient to be at the stroke centre with immediate access to cerebral angiography.

The concept of combining the advantages of IV thrombolysis (speed and certainty of initiation of therapy as well as widespread availability) and intra-arterial recanalisation therapy when possible (titrated dosing, mechanical aids to recanalisation, and possibly superior and earlier recanalisation) has been evaluated and suggested as a future treatment for patients with large vessel occlusion.

Aspirin
Large RCTs have demonstrated the beneficial effect of aspirin treatment in the secondary prevention of ischaemic stroke, with benefit being greater in patients receiving aspirin within the first three hours of stroke.

Giving aspirin in doses above 75mg daily to patients who have had an ischaemic stroke reduces the risk of a further stroke by about 13 per cent and the stroke risk per year from 7 per cent to 6 per cent. This equates to one stroke being prevented for every 100 patients prescribed aspirin.

Where patients are aspirin intolerant, alternatives, such as clopidogrel or dipyridamole, may be used and the combination of aspirin with these has been shown to be beneficial in certain circumstances.

Once 14 days have passed from symptom onset, guidelines advocate anticoagulation rather than antiplatelet therapy to prevent ischaemic stroke of cardioembolic origin.

In patients with stroke associated with 70-99 per cent internal carotid artery stenosis, carotid endarterectomy provides a 16 per cent five-year absolute risk reduction of stroke, with the benefit decreasing substantially if surgery is delayed for more than two weeks.

Regarding treatment for haemorrhagic stroke, there is consensus opinion that surgical evacuation of infratentorial intracerebral haemorrhage or supratentorial haematoma smaller than 1cm from the cortical surface is favourable compared with conservative medical treatment.

However, for all other supratentorial haemorrhagic stroke, surgery does not improve outcome compared with conservative medical treatment.

Section 4: Prognosis
In addition to specific medical treatments for stroke, guidelines recommend goal-oriented multidisciplinary rehabilitation (involving physiotherapists, occupational therapists, speech and language therapists, dieticians, psychologists, nurses and physicians) to minimise the functional consequences of the stroke and the impact of the stroke on the life of the patient and their carers, and to maximise the patient's autonomy.

For those patients who can return home because they can care for themselves or have the help of family or professional care, 'early supported discharge' schemes with rehabilitation that can be provided at home reduces death and dependency and is cost-effective.

Approximately 20-30 per cent of stroke patients die within a month. Stroke is the second leading cause of death and single largest cause of adult physical disability in the world. It costs the NHS about £2.8 billion per year but with the additional societal costs, it is estimated the national cost is approximately £7 billion per year.

Long-term disability
Very few stroke survivors make a complete recovery; nearly 12-18 per cent are left with speech problems, 25 per cent are unable to walk, 50 per cent have residual weakness and 24-53 per cent remain dependent on carers for day-to-day activities.

The risk of recurrent stroke is greatest soon after the first stroke: about 2-3 per cent of survivors of a first stroke have a recurrent stroke within the first 30 days, about 9 per cent in the first six months and 10-16 per cent within one year, which is about 15 times greater than the risk in the general population of the same age and sex.

After the first year, the average annual risk of recurrent stroke for the next four years falls to about 5 per cent.

This risk is about nine times the risk of stroke in the general population of the same age and sex.

These data emphasise the importance of preventing further strokes and the need for preventive measures to be instituted as soon as possible.

Resources
1. Nor AM, McAllister C, Louw SJ et al. Agreement between ambulance paramedicand physician-recorded neurological signs with Face Arm Speech Test (FAST) in acute stroke patients. Stroke 2004; 35: 1355-9.

2. 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: 727-34.

3. Langhorne P, Taylor G, Murray G et al. Early supported discharge services for stroke patients: a meta-analysis of individual patients' data. Lancet 2005; 365: 501-6.

4. DoH. National Stroke Strategy. 2007.

5. Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack: The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Cerebrovasc Dis 2008; 25: 457-507.

6. Royal College of Physicians Intercollegiate Stroke Working Party. National Clinical Guidelines on the Management of people of Stroke. 3rd Ed. 2008.

7. NICE. Stroke: Diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). CG68. London, NICE, 2008.

8. 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: 1695-703.

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