Stroke and transient ischaemic attacks

Essentials

1
Ischaemic strokes and transient ischaemic attacks (TIAs) are most commonly due to atherosclerotic thromboembolism of the cerebral vasculature or emboli from the heart. Other causes should be considered in younger patients, those presenting with atypical features or when evaluation is negative for the more common aetiologies.
2
Haemorrhagic and ischaemic strokes cannot be reliably differentiated on clinical grounds alone; therefore further imaging, most commonly computed tomography (CT) scanning, is required prior to the commencement of antiplatelet, thrombolytic or interventional therapies.
3
The risk of a completed stroke following a TIA can be high—up to 15% in the first week. Clinical scoring systems, such as the ABCD ² score, along with the results of brain and carotid vessel imaging, provide assessment tools for estimating stroke risk following TIA. Patients with TIA identified as at low risk for progression to stroke (e.g. ABCD ² <4, minimal large vessel disease on imaging) can be safely managed through integrated rapid-access TIA assessment clinics in an outpatient setting, with admission reserved for those at higher risk.
4
Differentiating strokes from other acute neurological presentations may be difficult in the emergency department. This issue has implications for the use of high-risk therapies such as thrombolysis.
5
The early phase of stroke management concentrates on airway and breathing, rapid neurological assessment of consciousness level, pupillary size, lateralizing signs and blood sugar measurements. Hyperglycaemia may worsen neurological outcome in stroke; therefore glucose should not be given in likely stroke patients unless a low blood sugar level is objectively demonstrated.
6
Outcomes in stroke patients are improved when they are admitted to a dedicated stroke unit. This involves a multidisciplinary approach to all aspects of stroke management.
7
Treating doctors should be fully aware of the risks/benefits and indications/contraindications of thrombolytic therapy in treating acute strokes. Currently, thrombolytic therapy should be considered for use in selected acute ischaemic strokes when administered within 4.5 hours of symptom onset, but controversies remain.
8
More complex imaging modalities, such as CT perfusion and diffusion/perfusion magnetic resonance imaging , continue to be evaluated in acute stroke workup in an attempt to better define the patient group that will benefit from aggressive vessel-opening strategies.
9
In the setting of acute large cerebral vessel occlusion, intra-arterial therapies such as clot retrieval devices continue to be evaluated and improved. The place of these interventions in acute stroke therapy is the subject of ongoing research. Recent trials suggest that clot retrieval may be safe in selected patients up to 24 hours after the onset of stroke symptoms.

Introduction

Cerebrovascular disease is the third most frequent 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) are defined as transient episodes of neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without acute infarction. 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.

Pathophysiology

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 the 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 (ICP) 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.

Ischaemic strokes

These are the results of several pathological processes ( Box 8.2.1 ):

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 thromboembolic 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, which 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.
Cerebral vasoconstriction may occur in association with subarachnoid haemorrhage (SAH), migraine and pre-eclampsia and with drugs such as sympathomimetics and cocaine, which may precipitate stroke.
Less common vascular disorders—such as arteritis, venous sinus thrombosis, sickle cell disease 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 congenital 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.

Box 8.2.1

Causes of stroke

Ischaemic stroke

Arterial thromboembolism
- Carotid and vertebral artery atheroma
- Intracranial vessel atheroma
- Small vessel disease—lacunar infarction
- Haematological disorders—hypercoagulable states
Cardioembolism
- Aortic and mitral valve disease
- Atrial fibrillation
- Mural thrombus
- Atrial myxoma
- Paradoxical emboli
- Hypoperfusion
Severe vascular stenosis or a combination of these factors
- Hypotension
- Vasoconstriction—drug-induced, post-SAH, pre-eclampsia
Other vascular disorders
- Arterial dissection
- Gas embolism syndromes
- Moyamoya disease
- Arteritis

Intracerebral haemorrhage

Hypertensive vascular disease
Lipohyalinosis and microaneurysms
Aneurysms
- Saccular
- Mycotic
Arteriovenous malformations
Amyloid angiopathy
Bleeding diathesis
- Anti-coagulation
- Thrombolytics
- Thrombocytopenia/disseminated intravascular coagulation
- Haemophilia
Secondary haemorrhage into a lesion—tumour or infarction

SAH, Subarachnoid haemorrhage.

Haemorrhagic stroke

Haemorrhagic stroke is the result of vessel rupture into the surrounding intracerebral tissue or subarachnoid space. SAH is the subject of a separate chapter in this book (see Chapter 8.3 ).

The neurological defect associated with an intracerebral haemorrhage (ICH) is the consequence of direct brain injury, secondary occlusion of nearby vessels, reduced cerebral perfusion caused by associated raised ICP and cerebral herniation. The causes of ICH include the following:

Aneurysmal 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, cerebral ischaemia from a ‘steal’ phenomenon.
Hypertensive vascular disease. Lipohyalinosis, mentioned earlier 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. Post-mortem pathological examination has found these changes, particularly in elderly patients with lobar haemorrhages.
Haemorrhage into an underlying lesion (e.g. tumour or infarction).
Drug toxicity from sympathomimetics and cocaine.
Anticoagulation and bleeding diatheses.

Risk factors for transient ischaemic attack/stroke and prevention

This particularly applies to cerebral ischaemic events, both TIAs and strokes. Non-modifiable risk factors for ischaemic stroke include the following:

Increasing age: the stroke rate more than doubles for each 10 years above age 55 years.
Gender: stroke is slightly more common in males than in females.
Family history.

In terms of 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 (AF), both chronic and paroxysmal. Anticoagulation is recommended to prevent cardioembolism where the risk:benefit ratio of anticoagulation (target international normalized ratio [INR] 2.0 to 3.0) favours this. Prediction tools, such as the CHADS ₂ (Congestive heart failure, Hypertension, Age >74, Diabetes and previous stroke / TIA) and CHA ₂ DS ₂ -VASc (Congestive heart failure, age, hypertension, sex, stroke / TIA history, vascular disease, diabetes) scores, have been developed to standardize the approach to primary stroke prevention in patients with non-valvular AF. The choice of appropriate anticoagulation should be tailored to each patient in consultation with his or her usual treating doctor and follow counselling and assessment of the risk:benefit ratio. The non vitamin K antagonist oral anticoagulants - or NOACs (apixaban, rivaroxaban or dabigatran) have been shown to be non-inferior to warfarin for the prevention of stroke in patients with non-valvular AF. Patients with valvular disease and AF should be commenced on warfarin unless there are contraindications to this therapy. Patients with contraindications to warfarin or very low stroke risk should initially receive aspirin.

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. Although early trials suggested some minor benefit, more recent studies have refuted this, and it is increasingly clear that intensive medical therapy in patients with asymptomatic carotid stenosis reduces stroke risk well below the reduction achieved with either endarterectomy or carotid stenting.

Other major cardiac conditions associated with increased TIA/stroke risk include endocarditis, mitral stenosis, prosthetic heart valves, recent myocardial infarction and left ventricular aneurysm. Less common ones include atrial myxoma, a patent foramen ovale and cardiomyopathies.

Secondary prevention involves detection and modification, if possible, of conditions that may have caused a TIA or stroke in order to prevent further events that could result in worse clinical outcomes. As well as the risk factors already mentioned, many other uncommon conditions, such as arterial dissection and prothrombotic states, may cause TIA and stroke. These are discussed later in the chapter.

Ischaemic stroke syndromes

The symptoms and signs of stroke or TIA correspond to the area of the brain affected by ischaemia or haemorrhage ( Table 8.2.1 ).

Table 8.2.1

Location of transient ischaemic attack

	Arterial territory
Symptom	Carotid	Either	Vertebrobasilar
Dysphasia	+
Monocular visual loss	+
Unilateral weakness ^a		+
Unilateral sensory disturbance ^a		+
Dysarthria ^b		+
Homonymous hemianopia		+
Dysphagia ^b		+
Diplopia ^b			+
Vertigo ^b			+
Bilateral simultaneous visual loss			+
Bilateral simultaneous weakness			+
Bilateral simultaneous sensory disturbance			+
Crossed sensory/motor loss			+

(Reproduced with permission from Hankey GJ. Management of first time transient ischaemic attack. Emerg Med . 2001;13:70–81.)

a Usually regarded as carotid distribution.

b Not necessarily a transient ischaemic attack if an isolated symptom.

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 such as a carotid bruit or AF may be present on clinical evaluation. For accurate delineation of the site of the brain lesion, exclusion of haemorrhage and assessment of the underlying cause, it is usually necessary to undertake imaging studies.

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. This system supplies the optic nerve, retina, frontoparietal lobes and most of the temporal lobes. Ischaemic injury involving the anterior cerebral circulation commonly has its origins in atherothrombotic disease of the ICA. Atherosclerosis 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 ( Box 8.2.2 ). Less commonly, lesions of the intracranial ICA and MCA may cause similar clinical features.

Box 8.2.2

Signs of middle cerebral artery occlusion

Homonymous hemianopia
Contralateral hemiplegia affecting face and arm more than leg
Contralateral hemisensory loss
Dysphasias with dominant hemispheric involvement (usually left)
Spatial neglect and dressing apraxia with non-dominant hemispheric involvement

Box 8.2.3

Differential diagnosis of stroke

Intracranial space-occupying lesion
Subdural haematoma
Brain tumour
Brain abscess
Postictal neurological deficit—Todd paresis
Head injury
Encephalitis
Metabolic or drug-induced encephalopathy
Hypoglycaemia, hyponatraemia, etc.
Wernicke-Korsakoff syndrome
Drug toxicity
Hypertensive encephalopathy
Multiple sclerosis
Migraine
Peripheral nerve lesions
Functional

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

The territory of the anterior cerebral artery 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 sensorimotor changes in the leg more than in the arm. More subtle changes of personality may occur with frontal lobe lesions, as may disturbances of micturition and conjugate gaze.

Major alterations of consciousness, with Glasgow Coma Scale scores below 8, imply bilateral hemispheric or brain stem dysfunction. The brain stem may be primarily involved by a brain stem stroke or secondarily affected by an ischaemic or haemorrhagic lesion elsewhere in the brain owing to a mass effect and/or increased ICP.

Posterior circulation ischaemia

Ischaemic injury in the posterior circulation involves the vertebra-basilar arteries and their major branches, which supply the cerebellum, brain stem, thalamus, medial 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.

Depending on the area and extent of involvement, brain stem and cerebellar stroke manifest as a combination of motor and sensory abnormalities that may be uni- or bilateral; cerebellar features of vertigo, nystagmus and ataxia; and cranial nerve signs, such as diplopia/ophthalmoplegia, facial weakness and dysarthria. Consciousness may also be affected.

Examples of cerebellar and brain stem stroke patterns include the following (this list is by no means exhaustive):

Ipsilateral cranial nerve with crossed corticospinal motor signs.
Lateral medullary syndrome: clinical features include sudden onset of vertigo, nystagmus, ataxia, ipsilateral loss of facial pain and temperature sensation (V) with contralateral loss of pain and temperature sensation of the limbs (anterior spinothalamic), ipsilateral Horner syndrome and dysarthria and dysphagia (IX and X).
Internuclear ophthalmoplegia manifesting as diplopia and a horizontal gaze palsy due to involvement of the medial longitudinal fasciculus (MLF).
‘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 brain stem reticular formation but cannot speak and is paralysed. Patients can move their eyes owing to sparing of the third and fourth cranial nerves in the midbrain.
Acute vertigo. Cerebellar and small strokes involving the cerebellum’s connections with the brain stem may present as acute ataxia and vertigo without other neurological signs. Signs that point to a central cause of vertigo include severe ataxia, inco-ordination and features outlined in the HINTS exam: maintained fixation on Head Impulse test, multidirectional Nystagmus and positive Test of Skew.
Acute deterioration of conscious state may be the presentation of acute basilar artery occlusion and should be in the differential diagnosis of coma for investigation.

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.

Clinical features

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 that of the acute onset of a neurological deficit over minutes; occasionally, however, there may be a more gradual or stuttering presentation over a period of hours. A past history of similar events suggestive of a TIA should be carefully sought. The presence of severe headache with the onset of symptoms may indicate ICH or SAH. However, headache may also occur with ischaemic strokes. Acute neck pain in association with neurological symptoms should raise the concern of arterial dissection or SAH.

A declining level of consciousness may indicate increasing ICP 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, the possibility of paradoxical embolization should be considered as well as dissection of the carotid or vertebral artery. Arterial dissection is often associated with neck pain and headaches/facial pain with or without a history of neck trauma. Trauma, if present, may be minor, such as a twisting or hyperextension/flexion injury sustained in a motor vehicle accident, in playing sports or caused by neck manipulation.

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

Examination

Central nervous system

This includes assessing the level of consciousness, pupillary size and reactivity, extent of neurological deficit, presence of neck stiffness and fundoscopy for signs of papilloedema and retinal haemorrhage. Quantifying the neurological deficit using a stroke scale, such as the 42-point National Institute of Health Stroke Scale (NIHSS), 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 greater than 22 are classified as severe.

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

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