Stroke and Transient Ischaemic Attacks

Cerebrovascular disease is the third highest cause of death in developed countries, after heart disease and cancer.

A stroke is an acute neurological injury secondary to cerebrovascular disease, either by infarction (80%) or by haemorrhage (20%).

The incidence of stroke is steady, and although mortality is decreasing, it is still a leading cause of long-term disability.

Transient ischaemic attacks (TIAs) have traditionally been defined as a focal loss of brain function attributed to cerebral ischaemia that lasts less than 24 hours, although most last considerably less time than this. Causes are similar to those of ischaemic stroke, particularly atherosclerotic thromboembolism related to the cerebral circulation and cardioembolism. Diagnosis of the cause of TIAs with appropriate management is important in order to prevent a potentially devastating stroke.


Brain tissue is very sensitive to the effects of oxygen deprivation. Following cerebral vascular occlusion a series of metabolic consequences may ensue, depending on the extent, duration and vessels involved, which can lead to cell death.

Reperfusion of occluded vessels may also occur, either spontaneously or via therapeutic intervention, with a potential for reperfusion injury. An area of threatened but possibly salvageable brain may surround an area of infarction. The identification of this so-called ischaemic penumbra, and therapeutic efforts to ameliorate the extent of irreversible neuronal damage, have been the subject of ongoing research efforts.

Large anterior circulation ischaemic strokes can be associated with increasing mass effect and intracranial pressure in the hours to days following onset. Secondary haemorrhage into an infarct may also occur, either spontaneously or related to therapy. Clinical deterioration often follows.

Table X1 | Causes of stroke
Ischaemic stroke
Arterial thromboembolism
– Carotid and vertebral artery atheroma
– Intracranial vessel atheroma
– Small vessel disease – lacunar infarction
– Haematological disorders – hypercoagulable states
– Aortic and mitral valve disease
– Atrial fibrillation
– Mural thrombus
– Atrial myxoma
– Paradoxical emboli
– Severe vascular stenosis or a combination of these factors]
– Hypotension ]
– Vasoconstriction – drug induced, post SAH, pre-eclampsia
Other vascular disorders
– Arterial dissection
–Gs embolism syndromes
– Moyamoya disease
– Arteritis
Intracerebral haemorrhage
Hypertensive vascular disease – Lipohyalinosis and microaneurysms
– Saccular
– Mycotic
Arterovenous malformations
Amyloid angiopathy
Bleeding diathesis
– Anticoagulation
– Thrombolytics
– Thrombocytopenia/disseminated intravascular coagulation
Secondary haemorrhage into a lesion – tumor or infarction

Ischaemic Strokes

These are the results of several pathological processes (Table X1):

  • Ischaemic strokes are most commonly due to thromboembolism originating from the cerebral vasculature, the heart, or occasionally the aorta. Thrombosis usually occurs at the site of an atherosclerotic plaque secondary to a combination of shear-induced injury of the vessel wall, turbulence and flow obstruction. Vessel wall lesions may also be the site of emboli that dislodge and subsequently occlude more distal parts of the cerebral circulation. Atherosclerotic plaque develops at the sites of vessel bifurcation. Lesions affecting the origin of the internal carotid artery (ICA) are the most important source of thromboemolic events. The more distal intracerebral branches of the ICA, the aorta and the vertebrobasilar system are also significant sites. Acute plaque change is likely to be the precipitant of symptomatic cerebrovascular disease, particularly in patients with carotid stenosis. Hence the most effective therapies will probably not only target the consequences of acute plaque change, such as thrombosis and embolism, but also aim for plaque stabilization using such agents as antiplatelet drugs, statins and antihypertensive drugs along the lines used in the management of acute coronary syndromes.
  • Approximately 20% of cerebrovascular events are due to emboli originating from the heart. Rarely emboli may arise from the peripheral venous circulation, the embolus being carried to the cerebral circulation via a patent foramen ovale.
  • Lipohyalinosis of small arteries is a degenerative process associated with diabetes and hypertension that mainly affects the penetrating vessels that supply areas such as the subcortical white matter, and is the postulated cause of lacunar infarcts.
  • Dissection of the carotid or vertebral arteries may cause TIAs and stroke. This may occur spontaneously or following trauma to the head and neck region, particularly in young people not thought to be at risk of stroke. Distal embolization from the area of vascular injury is the main pathological process involved.
  • Haemodynamic reduction in cerebral flow may occur as a result of systemic hypotension or severe carotid stenosis. In these cases cerebral infarction typically occurs in a vascular watershed area.
  • The cerebralvasoconstriction that may occur in association with subarachnoid haemorrhage (SAH), migraine and pre-eclampsia, and with drugs such as sympathomimetics and cocaine, may precipitate stroke.
  • Less common vascular disorders such as arteritis, venous and moyamoya disease may be causes of stroke.
  • Venous sinus thrombosis may occur spontaneously or in relation to an underlying risk factor such as an acquired or congenial prothrombotic disorder, dehydration or meningitis. The consequences depend on the extent and localization of the thrombosis. Stroke secondary to venous thrombosis is due to venous stasis, increased hydrostatic pressures and associated haemorrhage.

Haemorrhagic Stroke

Haemorrhagic stroke is the result of vessel rupture into the surrounding intracerebral tissue or subarachnoid space. Subarachnoid haemorrhage is the subject of a separate entry. The neurological defect associated with an intracerebral haemorrhage is the consequence of direct brain injury, secondary occlusion of nearby vessels, reduced cerebral perfusion caused by associated raised intracranial pressure, and cerebral herniation. The causes of intracerebral haemorrhage (ICH) include:

  • Anurysmal vessel dilatation. Vascular dilatation occurs at a site of weakness in the arterial wall, resulting in an aneurysm that expands until it ruptures into the subarachnoid space, and in some cases the brain tissue as well.
  • Arteriovenous malformation (AVM). A collection of weakened vessels exists as a result of abnormal development of the arteriovenous connections. AVMs may rupture to cause haemorrhagic stroke, or more rarely cause cerebral ischaemia from a ‘steel’ phenomenon.
  • Hypertensive vascular disease. Lipohyalinosis, mentioned above as a cause of microatheromatous infarcts, is also responsible for rupture of small penetrating vessels causing haemorrhage in characteristic locations, typically the putamen, thalamus, upper brain stem and cerebellum.
  • Amyloid angiopathy. Postmortem pathological examination has found these changes, particularly in elderly patients with lobar haemorrhages.
  • Haemorrhage into an underlying lesion, e.g., tumor or infarction.
  • Drug toxicity from sympathomimetics and cocaine.
  • Anticoagulation and bleeding diathese.


This particularly applies to ischaemic strokes. Non-modifiable risk factors for stroke include:

  • Increasing age: the stroke rate more than doubles or each 10 years above age 55.
  • Gender: slightly more common in males than females.
  • Family history.
  1. Primary Prevention

Hypertension is the most important modifiable risk factor. The benefit of antihypertensive treatment in stroke prevention has been well shown. The other major risk factors for atherosclerosis and its complications — diabetes, smoking and hypercholesterolaemia — often contribute to increased stroke risk. These should be managed according to standard guidelines. The most important cardiac risk factor for TIA and stroke is atrial fibrillation, both chronic and paroxysmal.

Warfarin is recommended to prevent cardioembolism, except in unsuitable patients. Those with contraindications to warfarin should initially receive aspirin. Other major cardiac risk factors include endocarditis, mitral stenosis, prosthetic heart valves, recent myocardial infarction and left ventricular aneurysm. Less common risk factors include atrial myxoma, a patent foramen ovale and cardiomyopathies.

A carotid bruit or carotid stenosis found in an otherwise asymptomatic patient is associated with an increased stroke risk. However, the role of carotid endarterectomy in these patients is controversial. In a highly selected patient group, the asymptomatic carotid atherosclerosis study (ACAS) showed a small but significant benefit in reduction of stroke or death at 5 years following surgery for angiographically proven stenosis >60% compared to medical therapy. The benefit was much lower than that achieved in symptomatic carotid stenosis shown in the North American Symptomatic Carotid Endarterectomy Study (NASCET 2), and can only be achieved with low perioperative mortality and stroke rates.

  1. Secondary Prevention

This relates principally to the prevention of a disabling stroke following a TIA or minor stroke, and will be covered under Investigation and Management of TIAs.

Ischaemic Stroke Syndromes

The symptoms and signs of stroke or TIA correspond to the area of the brain affected by ischaemia or haemorrhage.

In ischaemic brain injury the history and pattern of physical signs may correspond to a characteristic clinical syndrome according to the underlying cause and the vessel occluded. This has a bearing on the direction of further investigation and treatment decisions. Differentiating between anterior and posterior circulation ischaemia/infarction is important in this respect, but is not always possible on clinical grounds alone.

Determining the cause of the event is the next step. Once again, clues may be present on clinical evaluation. For accurate delineation of the site of the lesion, exclusion of haemorrhage and assessment of the underlying cause, it is usually necessary to undertake imaging studies.

  1. Anterior Circulation Ischaemia

The anterior circulation supplies blood to 80% of the brain and consists of the ICA and its branches, principally the ophthalmic, middle cerebral and anterior cerebral arteries. Hence this system supplies the optic nerve, retina, frontoparietal and most of the temporal lobes. Ischaemic injury involving the anterior cerebral circulation commonly has its origins in atherothrombotic disease of the ICA. Antherosclerosis of this artery usually affects the proximal 2 cm, just distal to the division of the common carotid artery. Advanced lesions may be the source of embolism to other parts of the anterior circulation, or cause severe stenosis with resultant hypoperfusion distally if there is inadequate collateral supply via the Circle of Willis. This is usually manifest by signs and symptoms in the middle cerebral artery (MCA) territory (Table X2). Less commonly, lesions of the intracranial ICA and MCA may cause similar clinical features.

Embolism to the ophthalmic artery or its branches causes monocular visual symptoms of blurring, loss of vision and field defects. When transient, this referred to as amaurosis fugax, or transient monocular blindness.

The anterior cerebral artery territory is the least commonly affected by ischaemia because of the collateral supply via the anterior communicating artery. If occlusion occurs distally or the collateral supply is inadequate, then ischaemia may occur. This manifests as sensory/motor changes in the leg — more so than the arm. More subtle changes of personality may occur with frontal lobe lesions, as may disturbances of micturition and conjugate gaze.

Major alteration of consciousness, with Glasgow Coma Scores <8, imply bilateral hemispheric or brainstem dysfunction. The brain stem may be primarily involved by a brainstem stroke or secondarily affected by an ischaemic or haemorrhagic lesion elsewhere in the brain, owing to a mass effect and/or increased intracranial pressure.

  1. Posterior Circulation Ischaemia

Ischaemic injury in the posterior circulation involves the vertebrobasilar arteries and their major branches which supply the cerebellum, brain stem, thalamus, medical temporal and occipital lobes. Posterior cerebral artery occlusion is manifested by visual changes of homonymous hemianopia (typically with macular sparing if the MCA supplies this part of the occipital cortex). Cortical blindness, of which the patient may be unaware, occurs with bilateral posterior cerebral artery infarction.

Brainstem and cerebellar involvement manifests as a combination of motor and sensory abnormalities, which may be uni– or bilateral; cerebellar features of vertigo nystagmus and ataxia; and cranial nerve signs of ophtalmoplegia, diplogia, facial weakness and dysarthria.

Specific brainstem syndromes include:

  • Lateral medullary syndrome: Clinical features include sudden onset of vertigo, nystagmus, ataxia, ipsilateral loss of facial pain and temperature sensation with contralateral loss of pain and temperature sensation of the limbs, ipsilateral Horner’s syndrome and dysarthria and dysphagia.
  • ’Locked-in’ syndrome: This is caused by bilateral infarction of a ventral pons, with or without medullary involvement. The patient is conscious due to an intact brainstem articular formation, but cannot speak and is paralyzed. Patients can move their eyes due to sparing of the third and fourth cranial nerves in the midbrain.
  1. Lacunar Infarcts

Lacunar infarcts are associated primarily with hypertension and diabetes. They occur in the small penetrating arteries supplying the internal capsule, thalamus and upper brain stem. Isolated motor or sensory deficits are most commonly seen.

Pre-Hospital Care

The pre-hospital care of the possible stroke patient involves the usual attention t the ABCs of resuscitation and early blood sugar measurement; however, it is unusual for interventions to be required.

Of potentially greater significance is the development of stroke systems (along the lines of trauma systems) in which the sudden onset of neurological signs and symptoms, identified in the pre-hospital evaluation as being consistent with acute stroke, is then used to direct patients to stroke centres with the facilities and expertise to manage them, particularly with regard to the delivery of thrombolytic agents. Closer hospitals without these capabilities may be bypassed. Studies of stroke centers have shown an increase in the use of thrombolytic agents and admission to stroke units. The effect on outcomes continues to be evaluated.

A pre-hospital evaluation tool that has been developed and validated is the Cincinatti Prehospital Stroke Scale or FAST: F –facial movements, A –arm movements, S –speech, and T –test. Pre-hospital personnel who identify patients with acute onset of neurological deficits identified using this simple scale can then notify the ED in order to mobilize appropriate staff and forewarn Radiology, so as to expedite assessment and imaging, particularly if thrombolysis is being considered.

Clinical Evaluation in the ED

  1. History

This includes the circumstances, time of onset, associated symptoms such as headache, and any resolution/progression of signs and symptoms. It may be necessary to take a history from a relative or friend, particularly in the presence of dysphasia or reduced conscious state.

The history of a stroke is usually of acute onset of a neurological deficit over minutes, but occasionally there may be a more gradual or stuttering nature to a presentation over a period of hours. A past history of similar events suggestive of a TIA should be carefully sought. The presence of a severe headache with the onset of symptoms may indicate ICH. However, headache may also occur with ischaemic strokes.

A declining level of consciousness may indicate increasing intracranial pressure due to an ICH or a large anterior circulation infarct — so-called malignant MCA infarction. It may also be caused by pressure on the brain stem by an infratentorial lesion such as a cerebellar haemorrhage.

The possibility of trauma or drug abuse should be remembered along with the past medical and medication history, particularly anticoagulant/antiplatelet therapy. Risk factors for vascular disease, cardiac embolism, venous embolism and increased bleeding should be sought.

In young patients with an acute neurological deficit, dissection of the carotid or vertebral artery should be considered. This is often associated with neck pain and headaches/facial pain with or without a history of neck trauma, which may be minor, as in a twisting or hyperextension/flexion injury sustained in a motor vehicle accident, playing sports or neck manipulation.

Cardioembolism tends to produce ischaemic injury in different parts of the brain, resulting in non-stereotypical recurrent TIAs, whereas atherothrombotic disease of the cerebral vessels tends to cause recurrent TIAs of a similar nature, particularly in stenosing lesions of the internal carotid or vertebrobasilar arteries.

  1. Examination
2.1    Central Nervous System

This includes assessing the level of consciousness, pupil size and reactivity, extent of neurological deficit, presence of neck stiffness and funduscopy for signs of papiloedema and retinal hemorrhage. Quantifying the neurological deficit using a stoke scale such as the 42-point National Institute of Health Stroke Scale (NIHSS) Opens in new window is useful in the initial assessment, and also for monitoring progress in a more objective way than clinical description alone. Strokes with a NIHSS score >22 are classified as severe.

In the case of TIA all clinical signs may have resolved. The average TIAA lasts less than 15 minutes.

2.2     Cardiovascular

This includes carotid auscultation and is directed towards findings associated with a cardioembolic source. A carotid bruit in a symptomatic patient is likely to predict a moderate to severe carotid stenosis. Conversely, the absence of a carotid artery disease as a cause of a TIA or stroke.

Major risk factors for cardioembolism that can be identified in the ED include atrial fibrillation, mitral stenosis, prosthetic heart valves, infective endocarditis, recent myocardial infarction, left ventricular aneurysm and cardiomyopathies. Obviously an ECG is an important part of this assessment.

Differential Diagnosis

Table X3 | Differential diagnosis of stroke
Intracranial space-occupying lesion
Subdural haematoma
Brain tumor
Brain abscess
Postictal neurological deficit – Todd’s paresis
Head injury
Metabolic or drug-induced encephalopathy
Hypoglycaemia, hyponatraemia etc.
Wernicke–Korsakoff syndrome
Drug toxicity
Hypertensive encephalopathy
Multiple sclerosis
Peripheral nerve lesions

The acute onset of stroke and TIA is characteristic; however, misdiagnoses can occur, even by experienced clinicians. The most common are seizures (particularly when there is associated Todd’s paresis),, systemic infection, brain tumor and toxic metabolic disorders. Others include subdural haematoma, hypertensive encephalopathy, encephalitis, multiple sclerosis, migraine and conversion disorder. This has implications when considering more aggressive stroke interventions, such as thrombolysis.

Complications of Stroke

CNS complications include:

  • Cerebral oedema and raised intracranial pressure (ICP). This is an uncommon problem in the first 24 hours following ischaemic stroke, but it may occur with large anterior circulation infarcts. It is more commonly seen with ICH, where acutely raised ICP may lead to herniation and brainstem compression in the first few hours.
  • Haemorrhagic transformation of ischaemic strokes may occur either spontaneously or associated with treatment.
  • Seizures can also occur and should be treated in the standard way. Seizure prophylaxis is not generally recommended.
  • Non-CNS complications include aspiration pneumonia, hypoventilation, DVT and pulmonary embolism, urinary tract infections and pressure ulcers. In the ED it is particularly important to be aware of the risk of aspiration.


Investigations of TIA and stroke often overlap, but the priorities and implications for management may differ significantly.


Standard investigation that may identify contributing factors to stroke/TIA or guide therapy include: a complete blood picture, blood glucose, coagulation profile, electrolytes, liver function tests and CRP (in selected cases). Arterial blood gases performed if the adequacy of ventilation is in doubt. An ECG should be performed to identify arrhythmias and signs of pre-existing cardiac disease.

Holter monitoring can be considered to identify paroxysmal arrhythmias, but has a low yield. A prothrombotic screen may be indicated, particularly in younger patients. Further investigations depend on the nature of the neurological deficit and other risk factors for stroke that are identified on evaluation, but usually involve a combination of brain, vascular and cardiac imaging.

TIAs and non-disabling strokes should be evaluated similarly in order to promptly diagnose and manage a potentially treatable process that might lead to a subsequent major stroke. The risk of a stroke following a TIA is now appreciated to be much higher than previously, and may be as high as 30% in the first week.

The ABCD stroke risks score from TIA has been developed and validated to evaluate the risk of a stroke in the first 7 days following a TIA. This has the potential to guide the urgency of investigations, such as carotid ultrasound, required to determine the underlying causes of the TIA.

In patients with an ABCD score <4 there is minimal short-term risk of stroke. With scores of 4, 5 and 6 the risk is 2.2%, 16.5% and 35%, respectively. Other patient groups are at increased risk of stroke independent of the ABCD scoring system. These include patients with diabetes, multiple TIAs within a short period, and patients with a probable or proven cardioembolic source. Diabetes has been incorporated in the recently published ABCD2 scoring system (see Further Reading).

Brain Imaging

A head CT or MRI scan is indicated in most patients with TIA to exclude lesions that occasionally mimic TIA, such as subdural haematomas and brain tumors. CT, and more particularly MRI, may show areas of infarction which match the symptoms of an ischaemic event that, on clinical grounds, has completely resolved. CT is less sensitive than MRI in detecting posterior territory ischaemic lesions, particularly in the brain stem. In TIAs due to atrial fibrillation or another known cardiac source, brain imaging to exclude ICH is necessary prior to commencing anticoagulation. The exception is in cases of emboli from endocraditis in which anticoagulation is contraindicated owing to the risk of secondary ICH.

Imaging Vessels
  • Ultrasound: If the aetiology of a TIA is likely to be carotid disease, such that there is a history of amaurosis fugax or hemispheric TIAs, with or without a carotid bruit, then a carotid ultrasound is the initial investigation of choice to investigate the presence and degree of a carotid stenosis.
  • Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA): This provides non-invasive imaging of the brain and major cerebral vasculature. MRA can show lesions suggestive of a vascular aetiology for TIAs, such as a stenosis due to atheromatous disease and dissection. MRI/MRA is not routine in TIA work-up, but may be indicated in more prolonged TIAs, in patients in whom an uncommon cause is suspected, or in younger patients.
  • Angiography: Formal angiography may be indicated in selected cases to confirm high-grade carotid stenosis and to confirm/exclude complete carotid occlusions shown on ultrasound. Angiography and MRI/MRA may be performed to investigate for intracranial cerebrovascular disease.
Cardiac Imaging

If the clinical evaluation indicates that a cardioembolic source is the most likely cause of a TIA, such as a patient with atrial fibrillation or a recent myocardial infarction, then echocardiography is a priority.

However, if there is no evidence of cardiac disease on clinical evaluation and the ECG is normal, then the yield of echocardiography is relatively low. A transthoracic echocardiogram (TTE) is the first line of investigation in cardiac imaging. A transoesophageal echocardiogram (TOE) is more sensitive than TTE in detecting potential cardiac sources of emboli, such as mitral valve vegetations, atrial/mural thrombi and atrial myxoma. It should be considered in patients with inconclusive or normal TTE with ongoing clinical concern for a cardioembolic source or patent foramen ovale. This particularly applies to younger patients with unexplained TIA/non-disabling stroke.

Imaging in Stroke

  • CT: In the setting of completed stroke the usual first-line investigation is a non-contrast CT scan. The main value of CT is its sensitivity in the detection of ICH and its ready availability. However, CT scans are often normal in the first hours following ischaemic stroke. In only about half of cases will there be changes detected at 24 hours after the onset of symptoms. The earliest sign of ischaemic stroke is loss of the cortical grey/white matter distinction in the affected arterial distribution. Early signs of cerebral oedema, such as effacement of the cortical sulci or compression of the ventricular system, are indicative of large infarcts. Occasionally a hyperdense clot sign will be seen in the region of the MCA.
  • A CT scan should be performed as soon as possible following stroke onset, and certainly within 24 hours. Urgent CT scanning is indicated in patients with a reduced level of consciousness, deteriorating clinical state, symptoms suggestive of ICH, associated seizures, prior to thrombolytic therapy, in younger patients, in patients who are on warfarin, and in cases of diagnostic doubt. A CT scan should also be performed to exclude haemorrhage prior to the commencement of antiplatelet therapies. It should, however, be noted that ICH may be subtle and difficult to diagnose, even for radiologists.
  • CT angiography is replacing formal angiography in the evaluation of primary ICH to identify the underlying cause, such as an aneurysm or AVM. It may also show the site of major vessel occlusion in ischaemic stroke. CT perfusion imaging is being evaluated as a technique for the detection of areas of hypoperfused brain at risk of infarction.
  • MRI: There are many magnetic resonance modalities available for imaging the brain in acute stroke. Even standard MRI is superior to CT in showing early signs of infarction, with 90% showing changes at 24 hours on T2-weighted images. Multimodal MRI typically involves additional modes such as gradient recalled echo (GRE) for the detection of acute and chronic haemorrhage, and diffusion-weighted imaging (DWI) for the detection of early ischaemia or infarction.
  • MRI: MR diffusion-weighted images show areas of reduced water diffusion in the parts of the brain that are ischemic and likely to be irreversibly injured. This occurs rapidly after vessel occlusion (less than an hour after stroke onset) and manifests as an area of abnormal high signal in the area of core ischaemia. Hence it is much more sensitive in detecting early ischaemia/infarction than standard T2-weighted MR scans (PWI) reveal areas of reduced or delayed cerebral blood flow. This area of the brain is likely to become infarcted if flow is not restored. The DWI and PWI lesions can then be compared. A PWI lesion significantly larger than a DWI lesion is a marker of potentially salvageable brain: the ischaemic penumbra. It is postulated that acute ischaemia stroke patients with this pattern are mostly likely to benefit from vessel opening strategies such as thrombolysis. Large areas of diffusion abnormality may also be marker for increased risk of ICH with thrombolysis. An MRA can be performed at the same time to identify a major vessel occlusion.

Recent studies have suggested that MRI is as accurate as CT in diagnosing acute ICH. This is significant, as it means that, where facilities are immediately available, CT may be bypassed in acute stroke and MRI can be used both to exclude ICH and to scan for ischaemia/infarction with DWI.

As already mentioned, other modalities such as PWI and MRA/MRV may also give important diagnostic information and influence treatment decisions. However, MRI may not be feasible in a significant number of stroke patients, due either to standard contraindications to MRI or other factors such as haemodynamic instability, impaired consciousness or vomiting and agitation. In one study the proportion of patients intolerant of MRI was 1:10.

MRI is indicated in strokes involving the brain stem and posterior fossa where CT has poor accuracy. MRA/MRV is particularly useful in the evaluation of unusual causes of stroke such as arterial dissection, venous sinus thrombosis and arteritis. Basilar artery thrombosis causes a brainstem stroke with an associated high mortality. If the diagnosis is suspected, urgent neurology consultation should be obtained. If MRA or CTA confirms the diagnosis, aggressive therapies such as thrombolysis may improve outcome.

Other investigations may be indicated, particularly in young people, in whom the cause of strokes/TIA may be obscure. These include tests to detect prothrombotic states and uncommon vascular disorders. A list of tests is potentially long and includes a thrombolphilia screen, vasculitic and luetic screens, echocardiography and angiography.


The treatment of cerebrovascular events must be individualized as determined by the nature and site of the neurological lesion and its underlying cause. The benefits and risks of any treatment strategy can then be considered and informed decisions made by the patient or their surrogate. This is particularly the case with the use of more aggressive therapies such as anticoagulation, thrombolysis and surgery.


The ED management of a TIA and stroke requires reassessment of the ABCSs and repeated blood glucose testing. Airway intervention may be necessary in the setting of a severely depressed level of consciousness, neurological deterioration, or signs of raised intracranial pressure and cerebral herniation. This is particularly the case with ICH, with its associated high mortality and morbidity rates.

Hypotension is very uncommon in stroke patients, except in the terminal phase of brainstem failure. Hypertension is much more likely to be associated with stroke because of the associated pain, vomiting and raised intracranial pressure and/or pre-existing hypertension, but rarely requires treatment. It may be a physiological response to maintain cerebral hypoxia and raised intracranial pressure. The use of antihypertensives in this situation may aggravate the neurological deficit. There is a paucity of scientific data to support the pharmacological lowering of blood pressure in the ischaemic stroke patient. Stroke guidelines recommend cautious and controlled lowering of a persistently raised blood pressure >220/140 mmHg or a mean arterial pressure greater than 130, using rapidly titratable intravenous drugs such as sodium nitroprusside, emolol or glycerine trinitrate at low initial doses, and with continuous haemodynamic monitoring in a critical care setting. The aim is for a 10–15% reduction.

Oral or sublingual nifedipine is contraindicated as it may cause a rapid uncontrolled fall in blood pressure that may aggravate cerebral ischaemia. Analgesia is appropriate if pain is thought to be contributory, and urinary retention should be excluded.

An elevated temperature can occur in stroke and should be controlled. It should also raise the suspicion of other possible causes for the neurological findings or an associated infective focus.


As already stated, the main aim of therapy in TIA and minor strokes is to prevent a major subsequent cerebrovascular event.

  • Antiplatelet therapy: Following CT scanning that excludes ICH, aspirin can be commenced at a dose of 300 mg and maintained at 75 – 150 mg/day in patients with TIAs or minor ischaemic strokes, and has been shown to be effective in preventing further ischaemic events. The ESPRIT trial showed a modest additional benefit from a combination of dipyridamole with aspirin, over aspirin alone. There was no increased rate of withdrawal of patients from the combination arm because of side effects of dipyridamole, principally headache. Clopidogrel may be substituted for aspirin if the patient is intolerant of aspirin or aspirin is contraindicated. There is some evidence that clopidogrel is more effective than aspirin in the prevention of vascular events, but at greater expense. The combination of aspirin and clopidogrel at this stage is not recommended as it does not appear to give an greater therapeutic benefits and there is increased bleeding risk. Anticoagulation with heparin and warfarin has not been shown to be superior to aspirin, except in cases of TIA/minor stroke due to cardioembolism (excluding endocarditis).
  • Anticoagulant therapy: Patients with a cardioembolic source of TIA should be considered for full anticoagulation following neurological consultation and normal brain imaging, with the exception of those with endocarditis, in whom the risk of haemorrhagic complications is increased.
  • Surgery: Trials have demonstrated a beneficial outcome of urgent surgery for symptomatic carotid stenosis in patients with anterior circulation TIAs and minor stroke with a demonstrated carotid stenosis of between 70% and 99%. The benefit of surgery may extend to lesser grades of stenosis down to 50% in selected patients. The patient’s baseline neurological state, comorbidities and operative mortality and morbidity rate also need to be assessed when considering surgery.
  • Other medical therapies: Risk factors for stroke and TIAs should be identified and treated. Statins should be considered regardless of cholesterol levels. The benefit of lowering LDL cholesterol levels using atorvastatin in preventing further cerebro- and cardiovascular events following an initial episode of cerebral ischaemia was demonstrated in the recent SPARCL study.

Ischaemic Stroke

A more active approach to the acute management of ischaemic stroke is seen as having the potential to improve neurological outcomes. The ED is the place where these important treatment decisions will largely be made.

Most patients with a stroke will require hospital admission for further evaluation and treatment, as well as for observation and possible rehabilitation. Studies of stroke units show that patients benefit from being under the care of physicians with expertise in stroke and a multidisciplinary team that can manage all aspects of their care.

  • Aspirin: In two large trials, aspirin, when administered within 48 hours of the onset of stroke, was found to improve the outcomes of early death or recurrent stroke compared to placebo. A CT scan should be performed to exclude ICH prior to commencing aspirin. The combination of low-dose aspirin and dipyridamole may confer some additional benefit.
  • Thrombolysis: Thrombolytic agents are seen as having an important place in the management of acute ischaemic stroke, although their use is still conversial. In Australia, the United Kingdom and the United States tPA has been approved for use in acute stroke patients when administered within 3 hours of onset. It is recommended that the inclusion and exclusion criteria that were used in the NINDS study should be strictly adhered to when deciding to administer tPA. For inclusion, treatment must be commenced within 3 hours of a known stroke onset and patients must have a CT scan excluding ICH. In the NINDS study, thrombolysis resulted in improved neurological outcomes in patients receiving tPA compared to placebo, with a 13% absolute increase in the number of patients having good neurological outcomes (numbers needed to treat = 8). In the thrombolysis group, there was a significant increase in intracerebral haemorrhage rate (6.4% versus O.6% in the placebo group), of which half were fatal, although there was no overall excess mortality.
  • Thrombolysis ... continues. Factors that may be associated with increased haemorrhage risk include increased age (especially >80 years), increased severity of stroke and early CT changes of a large ischaemic stroke. Studies of acute stroke patients given tPA outside controlled trials have yielded conflicting results. They suggest that when tPA is used by specialists in well-equipped stroke centers in accordance with strict guidelines, the complication rate for acute stroke patients can be similar to that achieved in the NINDs trial. However, protocol violations are associated with an increased risk of poor outcomes. Trials of thrombolysis are ongoing, with the aim of identifying patients most likely to benefit from reperfusion therapy, reducing the risk of ICH, and extending the time window for treatment, particularly through the use of advanced imaging modalities such as diffusion/perfusion MRI.
  • Anticoagulation: Anticoagulation should only be considered in stroke patients with a proven cardioembolic source. The risk of commencing anticoagulation soon after a vascular stroke is of inducing haemorrhagic transformation, which may result in clinical deterioration. A CT scan to exclude ICH and a neurological consultation should be obtained prior to considering anticoagulation in any patient with a stroke of likely cardioembolic origin.
  • Neuroprotection: A range of neuroprotective agents have been trialled in the setting of acute stroke in the hope that modulation of the ischaemic cascade of metabolic changes that follows vascular occlusion may result in improved neurological outcomes. At this stage, however, none of these therapies is recommended for the treatment of acute stroke.
  • Surgery: As for TIAs, patients with non-disabling stroke should be considered for investigation with carotid ultrasound to detect a significant stenosis that may be appropriate for urgent carotid endarterectomy. The use of endovascular stents in carotid surgery is also being developed and studied.

Large anterior circulation infarcts have a significant risk of developing cerebral oedema and raised ICP with associated clinical deterioration, particularly manifest by a declining conscious state with or without progression of other signs. Along with standard measures for managing raised ICP, there may be a place for decompressive craniotomy in selected cases. Intensive care and neurosurgical consultation should be considered.

related literatures:
    Adapted from: Textbook of Adult Emergency Medicine E-Book. Authored By Peter Cameron, George Jelinek, Anne-Maree Kelly, Lindsay Murray, Anthony F. T. Brown. References as cited include:
  1. Executive Committee of the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. Journal of the American Medical Association 1995; 273: 1421 – 1428.
  2. North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET). Beneficial effects of carotid endarterectomy in symptomatic patients with high grade carotid stenosis. New England Journal of Medicine 1991; 325: 445 – 453.
  3. Koutahri RU, Panciolli A, Liu T, et al. Cincinatti Pre Hospital Stroke Scale: reproducibility and validity. Annals of Emergency Medicine 1999; 33: 373 – 378.
  4. Goldstein LB, Samsa GP. Reliability of the National Institute of Health Stroke Scale: extension to non-neurologists in the context of a clinical trial. Stroke 1997; 28: 307 – 310.
  5. Rothwell PM, Giles MF, Flassmann E, et al. A simple score (ABCD) to identify individuals at high risk of stroke after transient ischaemic attack. Lancet 2005; 366: 29–36.
  6. Kidwell, CS, Chalela JA, Saver JL, et al. Comparison of MRI and CT for detection of acute intracerebral haemorrhage. Jounal of the American Medical Association 2004; 292: 1823–1834.
  7. The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT). Lancet 2006; 367: 1665–1673.
  8. CAPRIE Steering Committee. A randomized, blinded, control trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996: 348: 1329–1339.
  9. The Stroke Prevention by Aggressive Reduction in Cholesterol levels (SPARCL) Investigators. High dose atorvastatin after stroke or transient ischaemic attack. New England Journal of Medicine 2006: 355: 549–559.
  10. Duffy BK, Philips PA, Davis SM, et al. Evidence based care and outcomes of acute stroke managed in hospital specialty units. Medical Journal Australia 2003; 178: 318–323.
  11. International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among. 19435 patients with acute ischaemic stroke. Lancet 1997; 349: 1569–1581.
  12. CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomized placebo controlled trial of early aspirin use in. 20000 patients with acute ischaemic stroke. Lancet 1997; 349: 1641–1649.
  13. Hoffman J. Tissue plasimogen activator (tPA) for acute ischaemic stroke: why has so much been made of so little? Medical Journal Australia 2003; 179: 333–334.
  14. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (NINDS). Tissue plasminogen activator for acute ischaemic stroke. New England Journal of Medicine 1995; 333: 1581–1587.
  15. Albers GW. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. Journal of the American Medical Association 2000; 83: 1145–1150.
  16. Katzan IL, Furlan AJ, Lloyd LE, et al. Use of tissue type plasminogen activator for acute ischaemic stroke: the Cleveland Area Experience. Journal of the American Medical Association 2000; 283: 1511–1518.
  17. Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Trombolysis in Stroke (SITS-MOST): an observational study. Lancet 2007; 369: 275–282.
  18. Broderick, JP, Connolly S, Feldman E, et al. AHA/ASA Guidelines for the management of spontaneous intracerebral hemorrhage in adults. ICH. Stroke 2007; 38: 2001.
  19. Mayer S. Brun MC, Begtiup K, et al. Recombinant Factor 7a for acute ICH. New England Journal of Medicine 2005; 352: 777–785.
  20. Vahedi K, Hofmijer J, Juettler E, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomized controlled trials. Lancet Neurology 2007; 6: 215–222.
  21. Further Reading
    1. Rothwell PM. Atherothrombosis and ischaemic stroke. British Medical Journal 2007; 334: 379–381.
    2. Alberts MJ, Latchaw RE, Selman WR, et al. Brain Attack Coalition. Recommendations for comprehensive stroke centres: a consensus statement of the Brain Attack Coalition. Stroke 2005; 36: 1597–1616.
    3. Libman RB, Wirkowski E, Alvir J. Conditions that mimic stroke in the emergency department. Archives of Neurology 1995; 52: 1119–1122.
    4. Schriger DL, Kalafut M, Starkman S, et al. Cranial computed tomography interpretation in acute stroke. Physician accuracy in determining eligibility for thrombolytic therapy. Journal of the American Medical Association 1998; 279: 1293–1297.
    5. Adams HP Jr, Zoppo G, Alberts MJ, et al. AHA/ASA Guidelines for the early management of adults with ischaemic stroke. Stroke 2007; 38: 1655.
    6. Diener H, Bogousslavsky J, Brass LM, et al. on behalf ot the MATCH Investigators. Acetylsalicilic acid on a background of clopidogrel in high risk patients randomized after recent stroke or transient ischaemic attack: The Match trial results. Lance 2004; 364: 331–337.
    7. Sacco RL, Adams R, Albers G, et al. AHA/ASA Guidelines for the prevention of stroke with ischaemic stroke or transient ischaemic attack. Stroke 2006; 37: 577.
    8. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and Refinement of a score to predict very early stroke risk after transient ischaemic attack. Lancet 2007; 369:283–292.