	Extracranial	Intracranial
Tension/traction	Muscular headache	Intracranial tumour
	‘Tension headache’	Cerebral abscess
		Intracranial haematoma
Vascular	Migraine	Severe hypertension
Inflammatory	Temporal arteritis	Meningitis
	Sinusitis	Subarachnoid haemorrhage
	Otitis media
	Mastoiditis
	Tooth abscess
	Neuralgia

Assessment

In the assessment of a patient with headache, history is of prime importance. Specific information should be sought about the timing of the headache (in terms of both overall duration and speed of onset), the site and quality of the pain, relieving factors, the presence of associated features such as nausea and vomiting, photophobia and alteration in mental state, medical and occupational history and drug use.

Intensity of the pain is important from the viewpoint of management but is not a reliable indicator of the nature of underlying pathology. This said, sudden, severe headache and chronic, unremitting or progressive headache are more likely to have a serious cause.

Physical examination should include temperature, pulse rate and blood pressure measurements, assessment of conscious state and neck stiffness and neurological examination, including funduscopy (where indicated). Abnormal physical signs are uncommon, but the presence of neurological findings makes a serious cause probable. In addition, a search should be made for sinus, ear, mouth and neck pathology and muscular or superficial temporal artery tenderness.

Headache patterns

Some headaches have ‘classic’ clinical features: these are listed in Table 8.1.2. It must be remembered that, as with all diseases, there is a spectrum of presenting features and the absence of the classic features does not rule out a particular diagnosis. Every patient must be assessed on their merits and, if symptoms persist without reasonable explanation, further investigation should be undertaken.

Table 8.1.2 Classic clinical complexes and cause of headache

Preceded by an aura
Throbbing unilateral headache, nausea		Migraine
Family history
Sudden onset
Severe occipital headache; ‘like a blow’		Subarachnoid haemorrhage
Worst headache ever
Throbbing/constant frontal headache
Worse with cough, leaning forward		Sinusitis
Recent URTI
Pain on percussion of sinuses
Paroxysmal, fleeting pain
Distribution of a nerve		Neuralgia
Trigger manoeuvres cause pain		Neuralgia
Hyperalgesia of nerve distribution
Unilateral with superimposed stabbing
Claudication on chewing		Temporal arteritis
Associated malaise, myalgia		Temporal arteritis
Tender artery with reduced pulsation
Persistent, deep-seated headache
Increasing duration and intensity		Tumour: primary or secondary
Worse in morning		Tumour: primary or secondary
Aching in character
Acute, generalized headache
Fever, nausea and vomiting		Meningitis
Altered level of consciousness		Meningitis
Neck stiffness +/– rash
Unilateral, aching, related to eye
Nausea and vomiting		Glaucoma
Raised intraocular pressure
Aching, facial region
Worse at night		Dental cause
Tooth sensitive to heat, pressure

Investigation

For the vast majority of patients with headache no investigation is required. The investigation of suspected subarachnoid haemorrhage and meningitis is discussed elsewhere in this book. If tumour is suspected, the investigations of choice are magnetic resonance imaging (MRI) or a contrast-enhanced computed tomography (CT) scan. An elevated ESR may be supporting evidence for a diagnosis of temporal arteritis. With respect to sinusitis, facial X-rays are of very limited value.

Tension headache

The pathological basis of tension headaches remains unclear, but increased tension of the neck or cranial muscles is a prominent feature. A family history of headaches is common, and there is an association with an injury in childhood or adolescence. The most common precipitants are stress and alteration in sleep patterns.

Aspirin, non-steroidal anti-inflammatory agents (NSAIDs) and paracetamol have all been shown to be effective in the treatment of tension headaches, with success rates between 50% and 70%. Ibruprofen 400 mg or ketoprofen 25–50 mg appear to be the most effective, followed by aspirin 600–1000 mg and paracetamol 1000 mg.

Migraine

Migraine can be a disabling condition for the sufferer. Most migraine headaches are successfully managed by the patient and their general practitioner, but a small number fail to respond or become ‘fixed’, and sufferers may present for treatment at EDs. As most patients (up to 80% in some studies) have tried oral medications prior to presenting, parenterally administered agents are usually indicated for ED treatment.

Migraine is a clinical diagnosis, and in the ED setting a diagnosis of exclusion. Other causes of severe headache, such as subarachnoid haemorrhage and meningitis, must be ruled out before this diagnosis is made. In particular, the response of the headache to anti-migraine therapy should not be used to assume that the cause was migraine. There have been reports that the headaches associated with subarachnoid haemorrhage and meningitis have, on occasion, responded to these agents.

Pathophysiology

The pathophysiology of migraine is complex and not completely understood. It is probably the result of interaction between the brain and the cranial circulation in susceptible individuals.

The phenomenon of ‘cortical spreading depression’ is probably the event underlying the occurrence of an aura in migraine. This is a short-lasting depolarization wave that moves across the cerebral cortex. A brief phase of excitation is followed by prolonged depression of nerve cells. At the same time there is failure of brain ion homoeostasis, an efflux of excitatory amino acids from nerve cells, and increased energy metabolism. This phenomenon appears to be dependent on the activation of an N-methyl-D-aspartate receptor, which is a subtype of the glutamate receptor.

The headache pain of migraine seems to result from the activation of the trigeminovascular system. The trigeminal nerve transmits headache pain from both the dura and the pia mater. The triggers for the development of migraine headache are probably chemical and are thought to originate in the brain, the blood vessel walls and the blood itself. These triggers stimulate trigeminovascular axons, causing pain and the release of vasoactive neuropeptides, including calcium G-related peptide (CGRP) from perivascular axons. These neuropeptides act on mast cells, endothelial cells and platelets, resulting in increased extracellular levels of arachidonate metabolites, amines, peptides and ions. These mediators and the resultant tissue injury lead to a prolongation of pain and hyperalgesia.

Serotonin has also been specifically implicated in migraine. By activation of afferents, it causes a retrograde release of substance P. This in turn increases capillary permeability and oedema.

Classification and clinical features

Migraine is defined as an idiopathic recurring headache disorder with attacks that last 4–72 hours. Typical characteristics are unilateral location, pulsating quality, moderate or severe intensity, and aggravation by routine physical activity. There is also usually nausea, photophobia and phonophobia.

In some patients migraine is preceded by an ‘aura’ of neurological symptoms localizable to the cerebral cortex or brain stem, such as visual disturbance, paraesthesia, diplopia or limb weakness. These develop gradually over 5–20 minutes and last less than 60 minutes. Headache, nausea and/or photophobia usually follow after an interval of less than an hour.

Several variant forms of migraine have been defined, including ophthalmoplegic, abdominal, hemiplegic and retinal migraine, but all are uncommon. In ophthalmoplegic migraine the headache is associated with paralysis of one or more of the nerves supplying the ocular muscles. Horner’s syndrome may also occur. Abdominal migraine manifests as recurrent episodes of abdominal pain for which no other cause is found. Retinal migraine, which is fortunately very rare, involves recurrent attacks of retinal ischaemia which may lead to bilateral optic atrophy. Hemiplegic migraine is a stroke mimic.

Treatment

The complexity of the mechanisms involved in the genesis of migraine suggests that there are a number of ways to interrupt the processes to provide effective relief from symptoms.

A wide variety of pharmacological agents and combinations of agents have been tried for the treatment of migraine, with varying results. Interpreting the evidence is challenging, as the majority of the studies have small sample sizes, compare different agents or combinations of agents, are conducted in settings other than EDs, and the outcome measure(s) tested varies widely. Because the ED migraine population appears to be different from the general outpatient population, the data presented here are based on studies in EDs.

The effectiveness of commonly used agents is summarized in Table 8.1.3. Dosing and administration are summarized in Table 8.1.4. At present the most effective agents seem to be the phenothiazines (chlorpromazine, prochlorperazine, droperidol and possibly haloperidol) and the triptans, each of which has achieved > 70% efficacy in a number of studies. Note that triptans are contraindicated in patients with a history of ischaemic heart disease, uncontrolled hypertension or with the concomitant use of ergot preparations.

Table 8.1.3 Pooled effectiveness data from ED studies of the treatment of migraine. (Clinical studies, defined ‘success’ endpoint, minimum of 50 patients studied in aggregate, NNT calculated assuming placebo effectiveness rate of 25%)

Table 8.1.4 Drug dosing and administration

Agent	Drug dosing/administration
Chlorpromazine i.m.	12.5 mg intravenously, repeated every 20 minutes as needed to a maximum dose of 37.5 mg, accompanied by 1 L normal saline over 1 hour to avoid hypotension OR 25 mg in 1 L normal saline over 1 hour, repeated if necessary
Droperidol (i.m. or i.v.)	2.5 mg
Prochlorperazine (i.m. or i.v.)	10 mg/12.5 mg (depending on packaging)
Sumatriptan (s.c., i.n.)	6 mg SC, 20 mg i.n.
Metoclopramide (i.v.)	10–20 mg
Ketorolac (i.m. or i.v.)	30 mg i.v.; 60 mg i.m.
Tramadol (i.m.)	100 mg

Pethidine is not indicated for the treatment of migraine. Its reported effectiveness is only 56%, it has a high rate of rebound headache and it carries a risk of dependence. In two small RCTs haloperidol administered as 5 mg in 500 mL normal saline was reported to give significant pain relief in more than 80% of patients. Lignocaine (lidocaine) has been shown to be no more effective than placebo. The data on dihydroergotamine are difficult to interpret because it is often used in combination with other agents, e.g. metoclopramide; however, it has also been shown to be less effective than chlorpromazine and sumatriptan in acute treatment, and to have a high rate of unpleasant side effects. There are insufficient data to assess the effectiveness of CGRP receptor antagonists. Sodium valproate has also shown moderate effectiveness in small studies, but there are insufficient data to draw a valid conclusion. The efficacy of intravenous magnesium sulphate (1 or 2 mg) remains unclear. It was shown in a small placebo-controlled trial to be effective, but in another study the combination of magnesium with metoclopramide was less effective than metoclopramide and placebo.

There is some preliminary evidence that oral or i.v. dexamethasone, in addition to standard migraine therapy for selected patients, may reduce the proportion of patients who experience early recurrence (so-called rebound headache). Unfortunately, different studies have identified different groups who might benefit. There are insufficient data to recommend this as standard therapy.

Trigeminal neuralgia

Trigeminal neuralgia is a debilitating condition in which patients describe ‘lightning’- or a ‘hot poker’-like pain that is severe and follows the distribution of the trigeminal nerve. Individual episodes of pain last only seconds, but may recur repeatedly within a short period and can be triggered by minor stimuli such as light touch, eating or drinking, shaving or passing gusts of wind. It is most common in middle or older age.

Pathophysiology

Evidence suggests that the pathological basis of trigeminal neuralgia is demyelination of sensory fibres of the trigeminal nerve in the proximal (CNS) portion of the nerve root or rarely in the brain stem, most commonly due to compression of the nerve root by an overlying artery or vein.

Treatment

The mainstay of therapy for trigeminal neuralgia is carbamazepine. The usual starting dose is 200–400 mg/day in divided doses, increased by 200 mg/day until relief up to a maximum of 1200 mg/day. The average dose required is 800 mg/day. There is preliminary evidence that baclofen alone and the addition of lamotrigene to carbamazepine or phenytoin may be effective. Case series suggest that in acute crises of trigeminal neuralgia subcutaneous sumatriptan or intravenous infusions of lidocaine, phenytoin or fosphenytoin may be helpful. Early reports also suggest that for second-division trigeminal neuralgia, lignocaine administered intranasally by metered-dose inhaler provides acute but temporary relief.

A significant proportion of patients fail to obtain adequate relief from medical therapy. In these cases interventions such as microvascular decompression or partial destruction of the trigeminal nerve (for example by glycerol injections, radiofrequency thermal ablation or stereotactic gamma knife radiosurgery) may be indicated.

Controversies

• Choice of drug therapy for migraine.

• Role and timing of investigations in atypical migraine. CT or MRI may be indicated acutely to rule out other intracranial pathology.

• The role of corticosteroids in prevention of recurrent/ rebound migraine.

• Role and timing of investigations, in particular neuroimaging, for persistent or atypical headache.

• Second-line treatment for trigeminal neuralgia.

Introduction

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.

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 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.

Ischaemic strokes

These are the results of several pathological processes (Table 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 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 cerebral vasoconstriction 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 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.

Table 8.2.1 Causes of stroke

Intracerebral haemorrhage

Hypertensive vascular disease –

Lipohyalinosis and microaneurysms

Aneurysms

Saccular

Mycotic

Arteriovenous malformations

Thrombocytopenia/disseminated

intravascular coagulation

Haemophilia

Secondary haemorrhage into a lesion – tumour or infarction

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 chapter in this book (see Chapter 8.3). 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:

• 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 cause cerebral ischaemia from a ‘steal’ 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. tumour or infarction.

• Drug toxicity from sympathomimetics and cocaine.

• Anticoagulation and bleeding diatheses.

Prevention

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

• Increasing age: the stroke rate more than doubles for each 10 years above age 55.

• Gender: slightly more common in males than females.

• Family history.

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)¹ 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),² and can only be achieved with low perioperative mortality and stroke rates.

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 (Table 8.2.2).

Table 8.2.2 Location of TIA

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.

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. 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 (Table 8.2.3). Less commonly, lesions of the intracranial ICA and MCA may cause similar clinical features.

Table 8.2.3 Signs of middle cerebral artery (MCA) 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.

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 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 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 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.

Posterior circulation ischaemia

Ischaemic injury in the posterior circulation involves the vertebrobasilar 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.

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 ophthalmoplegia, diplopia, 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 paralysed. Patients can move their eyes due to sparing of the third and fourth cranial nerves in the midbrain.

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 to 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 centres 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.³ 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

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.

Examination

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 papilloedema and retinal haemorrhage. Quantifying the neurological deficit using a stroke scale such as the 42-point National Institute of Health Stroke Scale (NIHSS)⁴ 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 TIA lasts less than 15 minutes.

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 bruit does not exclude significant 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 8.2.4)

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 tumour 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.

Table 8.2.4 Differential diagnosis of stroke

Intracranial space-occupying lesion

Subdural haematoma

Brain tumour

Brain abscess

Postictal neurological deficit – Todd’s 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

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

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

General

Standard investigations 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 thought, and may be as high as 30% in the first week. The ABCD stroke risk score from TIA has been developed and validated to evaluate the risk of a stroke in the first 7 days following a TIA.⁵ This has the potential to guide the urgency of investigations, such as carotid ultrasound, required to determine the underlying causes of the TIA. The scoring system is outlined in Table 8.2.5. 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).

Table 8.2.5 The ABCD TIA Risk Score

ABCD	Risk factor	Score
Age	Below 60	0
	Above 60	1
Blood pressure	BP > systolic 140 mmHg, and/or diastolic 90 mmHg	1
Clinical	Unilateral weakness of face, arm, hand or leg	2
	Speech disturbance without weakness	1
Duration	Symptoms lasted >60 min	2
	Symptoms lasted 10–60 min	1
	Symptoms lasted < 10 min	0

(From 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)

Imaging in stroke

Brain imaging

• 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. MR diffusion-weighted images show areas of reduced water diffusion in the parts of the brain that are ischaemic 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 MRI modalities or CT. Perfusion-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 ischaemic stroke patients with this pattern are most likely to benefit from vessel opening strategies such as thrombolysis. Large areas of diffusion abnormality may also be a 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.⁶ This is significant, as it means that, where facilities are immediately available, CT may be bypassed in acute stroke and MRI can be used to both to exclude ICH and to scan for ischaemia/infarction with DWI. As already mentioned, other modalities such 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 thrombophilia screen, vasculitic and luetic screens, echocardiography and angiography.

Treatment

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.

General

The ED management of a TIA and stroke requires reassessment of the ABCDs 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 perfusion pressure in the face of 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, esmolol 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.

TIAs

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 ⁷ showed a modest additional benefit from a combination of dipyridamole with aspirin, over aspirin alone. There was no increased risk of bleeding complications, but there was a significantly 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.⁸ The combination of aspirin and clopidogrel at this stage is not recommended as it does not appear to give any 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%.² 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.⁹

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.¹⁰

• 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.^11,¹² 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 controversial.¹³ 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 study¹⁴ 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 0.6% in the placebo group), of which half were fatal, although there was no overall excess mortality. 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.¹⁵^–¹⁷ They suggest that when tPA is used by specialists in well-equipped stroke centres 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 cardio-embolic 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.

Buy Membership for Emergency Medicine Category to continue reading. Learn more here