Edited by Anne-Maree Kelly
OUTLINE
8.1 Headache 386
8.2 Stroke and transient ischaemic attacks 390
8.3 Subarachnoid haemorrhage 400
8.4 Altered conscious state 405
8.5 Seizures 411
8.6 Syncope and vertigo 416
8.7 Weakness 420
8.1 Headache
Anne-Maree Kelly
Essentials
1 The pathophysiological basis of headache is traction or inflammation of extracranial structures, the basal dura or the large intracranial arteries and veins or dilatation/distension of cranial vascular structures.
2 Severity of headache is not a reliable indicator of the underlying pathology.
3 History is of paramount importance in the assessment of headache.
4 A normal physical examination does not rule out serious pathology.
5 Sudden, severe headache or chronic, unremitting headache is more likely to have a serious cause and should be investigated accordingly.
6 NSAID and paracetamol are effective treatment for tension headache.
7 As most patients have tried oral medications prior to attending the emergency department, parenterally administered agents are usually indicated for treatment of migraine.
8 Based on current evidence, the most effective agents for treating migraine are phenothiazines and triptans. Pethidine is not indicated because it is less effective than other agents, has a high rebound headache rate and carries the potential for the development of dependence.
9 Carbamazepine is the agent of choice for treatment of trigeminal neuralgia.
Introduction
Headache is a common ailment that is often due to a combination of physical and psychological factors. The vast majority are benign and self-limiting and are managed by patients in the community. Only a very small proportion of patients experiencing headache attend emergency departments (ED) for treatment. The challenges are to distinguish potentially life-threatening causes from the more benign and to manage effectively the pain of headache.
Aetiology, pathophysiology and pathology
The structures in the head capable of producing headache are limited. They include:
extracranial structures, including skin and mucosae, blood vessels, nerves, muscles and fascial planes
the main arteries at the base of the skull (as arteries branch they progressively lose the ability to produce painful stimuli)
the great venous sinuses and their branches and
the basal dura and dural arteries, but to a lesser extent than the other structures.
The bulk of the intracranial contents, including the parenchyma of the brain, the subarachnoid and pia mater and most of the dura mater, are incapable of producing painful stimuli.
The pathological processes that may cause headache are:
Tension. This usually refers to contraction of muscles of the head and/or neck and is thought to be the major factor in the so-called ‘tension headache’.
Traction. Traction is caused by stretching of intracranial structures due to a mass effect, such as with a space-occupying lesion. Pain caused by this mechanism is characteristically constant, but may vary in severity.
Vascular processes. These include dilatation or distension of vascular structures and often results in pain that is throbbing in nature.
Inflammation. This may involve the dura at the base of the skull or the nerves or soft tissues of the head and neck. This mechanism is responsible for the initial pain of subarachnoid haemorrhage and meningitis and for sinusitis.
The pathophysiological causes of headache are summarized in Table 8.1.1.
Table 8.1.1
A pathophysiological classification of headache
Clinical features
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 a 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
URTI: upper respiratory tract infection.
Clinical investigations
For the 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 erythrocyte sedimentation rate (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 (acetaminophen) 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. Of particular note, the response of a headache to antimigraine 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 a chronic neurovascular disorder characterized by dysfunction of the central and peripheral nervous system and intracranial vasculature.
The headache pain of migraine seems to result from the activation of the trigeminovascular system. 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. 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 brainstem, 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. For mild to moderate migraine headache in patients who have not taken other medication, aspirin 900 mg combined with metoclopramide 10 mg is effective. Most ED patients, however, have either tried their usual medication or have significant nausea or vomiting making oral therapy inappropriate.
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 appear to be the phenothiazines (chlorpromazine and prochlorperazine) 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 in adults, 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 (IV) |
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 |
|
Prochlorperazine (IM or IV) |
10 mg/12.5 mg (depending on packaging) |
|
Sumatriptan (SC, IN) |
6 mg SC, 20 mg IN |
|
Metoclopramide (IV) |
10–20 mg |
|
Ketorolac (IM or IV) |
30 mg IV, 60 mg IM |
|
Tramadol (IM) |
100 mg |
Pethidine (meperidine) 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. 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. Sodium valproate and haloperidol have also shown moderate effectiveness in small studies, but there are insufficient data to draw a valid conclusion or recommend them as treatment options. Lignocaine (lidocaine) has been shown to be no more effective than placebo. 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.
Rebound or recurrent headache is common in ED patients treated for migraine (approximately 30%). There is evidence that oral or IV dexamethasone, in addition to standard migraine therapy for selected patients, reduces the proportion of patients who experience early recurrence (so-called rebound headache). A meta-analysis of published papers reports a 26% reduction in the relative risk of headache recurrence within 72 hours. Doses used were 10 mg IV or 8 mg orally.
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.
Aetiology and 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 brainstem, most commonly due to compression of the nerve root by an overlying artery or vein.
Trigeminal neuralgia is classified as classic trigeminal neuralgia (no cause identified) and symptomatic trigeminal neuralgia (secondary to another condition). Characteristics associated with symptomatic trigeminal neuralgia are trigeminal sensory deficits and bilateral involvement.
Clinical investigations
In approximately 15% of cases, there is a structural cause for trigeminal neuralgia. For this reason, there is some support for routine neuroimaging (CT, MRI) in these patients. Electrophysiological assessment of trigeminal reflexes can also be helpful in distinguishing classic from symptomatic trigeminal neuralgia. The choice between the two approaches will depend on availability, expertise, cost and patient and treating clinician preference.
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. Where available, oxcarbazepine 600–1800 mg/day is an effective alternative. For patients who fail first-line therapy, there is some evidence to support the addition of lamotrigine or a change to baclofen. Referral for consideration of surgery is appropriate in patients who are refractory to medical therapy.
Temporal (giant cell) arteritis
Giant cell arteritis is the most common form of vasculitis in patients aged over 50 years. It affects large and middle-sided blood vessels with a predisposition for the cranial arteries arising from the carotid arteries. Loss of vision is the most common severe complication. Involvement of extracranial arteries including the aorta is more frequent than previously assumed. Inflammation markers in blood are usually elevated, but specific laboratory tests for the diagnosis of giant cell arteritis are not available. Imaging using ultrasonography, magnetic resonance imaging and positron emission tomography can be useful to confirm, localize and assess the extent of vascular involvement. Temporal artery biopsy is the gold standard for diagnosis. Glucocorticoids are still the standard therapy (50–100 mg/day). Patients with acute visual changes secondary to giant cell arteritis should receive parenteral corticosteroid therapy and be admitted until their condition stabilizes.
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.
Investigation of trigeminal neuralgia.
Second-line treatment for trigeminal neuralgia.
Further reading
1. American Academy for Neurology. AAN summary of evidence-based guideline for clinicians: trigeminal neuralgia.<https://www.aan.com/practice/guideline/uploads/303.pdf>[Accessed Jan. 2013].
2. Colman I, Friedman BW, Brown MD, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomized controlled trials for preventing recurrence. Br Med J. 2008;336:1359–1361.
3. Derry CJ, Derry S, Moore RA. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012;2:CD009665.
4. Friedman BW, Kapoor A, Friedman MS, et al. The relative efficacy of meperidine for the treatment of acute migraine: a meta-analysis of randomized controlled trials. Ann Emerg Med. 2008;52:705–713.
5. Kelly AM, Holdgate A. Emergency care evidence in practice series, emergency care community of practice: migraine in the emergency department Melbourne: National Institute of Clinical Studies; 2006; <http://www.nhmrc.gov.au/_files_nhmrc/file/nics/material_resources/Management%20of%20acute%20migraine%20colour.pdf>[Accessed Jan. 2013].
6. Kelly AM. Specific pain syndromes: headache. In: Mace S, Ducharme J, Murphy M, eds. Pain Management and procedural sedation in the emergency department. New York: McGraw-Hill; 2006.
7. Kelly AM, Walcynski T, Gunn B. The relative efficacy of phenothiazines for the treatment of acute migraine: a meta-analysis. Headache. 2009;49:1324–1332.
8. Sumamo Schellenberg E, Dryden DM, et al. Acute migraine treatment in emergency settings Comparative effectiveness review No 84 (Prepared by the University of Alberta Evidence-based Practice Center under Contract No 290-2007-10021-I.) AHRQ Publication No 12(13)-EHC142-EF Rockville, MD: Agency for Healthcare Research and Quality; 2012; <www.effectivehealthcare.gov/reports/final.cfm>[Accessed Jan. 2013].
9. Yoon YJ, Kim JH, Kim SY, et al. A comparison of efficacy and safety of non-steroidal anti-inflammatory drugs versus acetaminophen in the treatment of episodic tension-type headache: a meta-analysis of randomized placebo-controlled trial studies. Korean J Fam Med. 2012;33:262–271.
8.2 Stroke and transient ischaemic attacks
Philip Aplin and Mark Morphett
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 CT scanning, is required prior to the commencement of antiplatelet, thrombolytic or interventional therapies.
3 The risk of a completed stroke following a TIA is high – up to 15% in the first week. Clinical scoring systems, such as the ABCD2 score, have been proposed as an assessment tool for a stroke risk following TIA. Patients with TIA identified as low risk for progression to stroke (e.g. ABCD2<4) are increasingly managed through integrated rapid 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 conscious level, pupil size and lateralizing signs and blood sugar measurements. Hyperglycaemia may worsen neurological outcome in stroke and so 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, tPA 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 MRI, continue to be evaluated in acute stroke work-up in an attempt to define better 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.
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) 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 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
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
Anticoagulation
Thrombolytics
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 (ICH) 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 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 brainstem 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 TIA/stroke and prevention
This particularly applies to cerebral ischaemic events, both TIAs and strokes. Non-modifiable risk factors for ischaemic stroke include:
increasing age: the stroke rate more than doubles for each 10 years above age 55.
gender: stroke is slightly more common in males than 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. Warfarin is recommended to prevent cardioembolism where the risk:benefit ratio of anticoagulation (target INR 2.0–3.0) favours this. Prediction tools, such as the CHADS2 and CHA2DS2-VASc scores, have been developed to standardize the approach to primary stroke prevention in patients with non-valvular AF. Recently, an oral direct thrombin inhibitor (dabigatran) has been shown to be non-inferior to warfarin for stroke prevention in a large industry sponsored trial (the RE-LY trial). On the basis of this trial, dabigatran has been approved for use as an alternative to warfarin with rapid uptake of this medication in the community. Those 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. While 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 that 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 may 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 will be 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 8.2.2).
Table 8.2.2
Location of TIA
*Usually regarded as carotid distribution.
**Not necessarily a transient ischaemic attack if an isolated symptom. Reproduced with permission from Hankey GJ. Management of first time transient ischaemic attack. Emerg Med 2001;13:70–81.
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 atrial fibrillation, 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.
Patterns of clinical features
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 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 brainstem 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, brainstem, 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, brainstem and cerebellar stroke manifest 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, such as diplopia/ophthalmoplegia, facial weakness and dysarthria. Consciousness may also be affected.
Examples of brainstem stroke patterns include (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’s syndrome and dysarthria and dysphagia (IX and X)
internuclear ophthalmoplegia manifesting as diplopia and a horizontal gaze palsy due to involvement of the median 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 brainstem reticular 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.
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 brainstem. 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 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 or SAH. 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 brainstem 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. Trauma if present may be minor, such as 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), 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 emergency department (ED) include AF, mitral stenosis, prosthetic heart valves, infective endocarditis, recent myocardial infarction, left ventricular aneurysm and cardiomyopathies.
Differential diagnosis (Table 8.2.4)
The acute onset of stroke and TIA is characteristic, however, misdiagnoses (the so-called ‘stroke mimics’) can occur. The most common stroke mimics are seizures (particularly when there is associated Todd’s paresis), hypoglycaemia, 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
CNS complications of stroke 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 occur and should be treated in the standard way. Seizure prophylaxis is not generally recommended.
Non-CNS complications include aspiration pneumonia, hypoventilation, deep venous thrombosis and pulmonary embolism, urinary tract infections and pressure ulcers. In the ED, it is particularly important to be aware of the risk of aspiration.
Clinical investigations
The investigations of TIA and stroke often overlap, but the priorities and implications for management may differ significantly.
General investigations
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, fasting lipids and, in selected cases, C-reactive protein (CRP). Arterial blood gases should be 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 in unselected patients (i.e. those without any history suggestive of symptomatic arrhythmias or background of structural heart disease). 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.
Imaging in TIAs
Prompt diagnosis and management of patients presenting with TIAs and non-disabling strokes has been shown to reduce the risk of subsequent stroke by up to 80%. Risk stratification for patients presenting with TIAs can guide the urgency of investigations required to determine the underlying cause of the TIA – this is discussed more fully below.
Brain imaging
A head computed tomgraphy (CT) or magnetic resonance imaging (MRI) scan is indicated in all patients with TIA to exclude lesions that occasionally mimic TIA, such as subdural haematomas and brain tumours. 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 brainstem. In TIAs due to AF or another known cardiac source, brain imaging to exclude ICH is necessary prior to commencing anticoagulation. The exception is in cases of emboli from endocarditis in which anticoagulation is contraindicated owing to the increased risk of secondary ICH.
Imaging vessels
Ultrasound: if the aetiology of a TIA is likely to be carotid disease, with or without a carotid bruit, then a carotid ultrasound remains the most commonly utilized initial investigation to investigate the presence and degree of a carotid stenosis.
CT angiography (CTA): CTA is increasingly being used to image vessels in cases of TIA – commonly in conjunction with contrast studies examining cerebral perfusion. Advantages include ease of access and avoidance of further delay waiting for second modality imaging. Disadvantages include exposure to contrast dye and ionizing radiation.
Magnetic resonance imaging 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. The use of formal angiography has declined in recent years, with greater use of both CT angiography and MRA studies as confirmatory tests where atheroma is found on carotid ultrasound.
Cardiac imaging
If the clinical evaluation indicates that a cardioembolic source is a likely cause of a TIA, 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 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. TOE should be considered in patients with inconclusive or normal TTE with ongoing clinical concern of a cardioembolic source or patent foramen ovale. This particularly applies to younger patients with unexplained TIAs/non-disabling stroke.
Imaging in stroke
Brain imaging
Computed tomography: 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 24 hours after the onset of symptoms.
The early signs of ischaemic stroke include loss of the cortical grey/white matter distinction and hypoattenuation in the affected arterial distribution (e.g. the insular ribbon sign and obscuration of the lenticulostriate territory in MCA infarcts). Occasionally, a hyperdense clot sign will be seen in the region of the MCA. As well as the presence of haemorrhage, the degree of acute ischaemic change, typically change affecting greater than a third of the MCA territory, has been used to exclude patients from thombolytic trials due to possible lack of therapeutic benefit and increased haemorrhage risk. The degree of acute ischaemic change on plain CT can be more reliably quantified by using the ASPECTS score.
A CT scan should be performed as soon as possible following stroke onset. 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 perfusion/CT angiography: CT perfusion studies are increasingly being used in the setting of acute stroke. Following IV contrast injection, an area of brain is imaged and analysed using computer software with respect to the cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT). Using predetermined cut-offs of these values, the areas of likely irreversibly infarcted brain (infarct core) and at risk ischaemic brain (ischaemic penumbra) can be demonstrated (E-Fig. 8.2.1). A CT angiogram which includes the carotid vessels is also performed to determine if there is a site of large vessel occlusion. This technology is seen as offering an alternative to diffusion/perfusion MRI and MRA as it is more readily available, generally quicker and less subject to artefact. However, the technique is still in evolution and involves iodinated contrast and radiation exposure.
E-FIG. 8.2.1 CT perfusion study of an L MCA stroke. (A) mean transit time; (B) cerebral blood volume; (C) cerebral blood flow.
CT angiography (CTA): CTA is the imaging modality of choice in evaluation of primary ICH to identify the underlying cause, such as an aneurysm or AVM. CTA should be performed in cases of stroke due to suspected arterial dissection and basilar artery thrombosis.
Formal angiography is required occasionally in acute stroke. It will be required if intra-arterial therapy, such as embolectomy, is being considered. This only occurs in specialized centres.
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) and fluid-attenuated inversion recovery (FLAIR) sequences for the detection of acute and chronic haemorrhage and diffusion-weighted imaging (DWI) for the detection of early ischaemia or infarction. MR DWI 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 MRI scans (PWI) reveal areas of reduced or delayed cerebral blood flow following MRI contrast injection. 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. DWI/PWI imaging is generally considered to be easier to interpret and more reliable than CT perfusion studies. However, MRI may not be as available or feasible. A significant number of patients are unsuitable for MRI and the multimodal imaging takes longer than CT which increases the risk of motion artefact and potential delay to treatment. Radiation and iodinated contrast exposure are absent in MRI.
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 plus or minus PWI and MRA.
The place of advanced imaging modalities, such as CT perfusion and DWI/PWI MRI, in acute stroke work-up is evolving. For over a decade now it has been hoped that the information provided by these studies will help better select patients who will benefit from aggressive stroke therapies, such as thrombolysis, and extend the current narrow time window for such treatment on the basis of the existence of a significant ischaemic penumbra. They are now a common feature of acute stroke imaging work-up protocols if thrombolysis is being considered. However, at this point, high level evidence of improved clinical outcomes in acute stroke patients based on this approach is lacking. To date, the only published phase III trial (DIAS 2) of thrombolysis 3–9 hours post-onset using penumbral section criteria as shown on advanced imaging CT perfusion or DWI\PWI MRI was negative for the primary outcome of improved neurological outcome. The field of stoke imaging is changing rapidly and ongoing research investigating advanced imaging modalities as a basis for patient selection and mode of treatment is intense.
MRI is indicated in strokes involving the brainstem 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 specialist consultation should be obtained. If MRA or CTA confirms the diagnosis, aggressive therapies, such as thrombolysis, may improve outcome.
Other investigations
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. The 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. It is 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.
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. 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 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.
Pre-hospital evaluation and early hospital triage tools that have been developed for rapid identification of stroke include the Cincinnati Prehospital Stroke Scale or FAST (F – facial movements, A – arm movements, S – speech, and Τ – test) and the Rosier score. Pre-hospital personnel who identify patients with acute onset of neurological deficits consistent with stroke, using these simple scales, can be potentially directed to stroke centres and in-hospital acute stroke responses can be activated so as to expedite assessment and imaging, particularly if thrombolysis is being considered.
General measures
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.
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 and usually settles spontaneously. 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. The recently published SCAST trial of candesartan commenced within 30 hours of symptom onset and continued for 7 days in patients with ischaemic (85%) or haemorrhagic (15%) stroke and systolic blood pressure≥140 mmHg showed no benefit in functional outcomes and suggested possible harm. This study excluded patients receiving thrombolysis. Hypertension in the setting of thrombolytic therapy is managed according to local protocols.
Analgesia is appropriate if pain is thought to be contributory and urinary retention should be excluded prior to commencing antihypertensive therapy.
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. Hyperglycaemia should be treated appropriately, however, intensive euglycaemic therapy is not indicated.
TIA
Risk stratification
As already stated, the main aim in therapy in TIAs and minor strokes is to prevent a major subsequent cerebrovascular event. While traditionally patients presenting with TIAs have been hospitalized for work-up, more recently, there has been a move away from this to a more tailored approach where patients are risk stratified into higher risk (inpatient work-up) and lower risk patients who may be suitable for early outpatient follow up, for example in coordinated rapid access ‘TIA clinics’.
One popular tool for risk stratification in this population is the ABCD2 score. The ABCD2 stroke risk score for TIA has been developed and validated to evaluate the very early risk of a stroke following a TIA. The scoring system is shown in Table 8.2.5. In patients with an ABCD2 score less than 4, there is minimal short-term risk of stroke. With scores of 4–5 and 6–7, the 2-day risk is 4.1%, and 8.1%, respectively. The use of the ABCD2 score is not universally accepted, however, as ongoing validation studies have had mixed results. Other risk stratification strategies, such as the recently published M3T model, use a combination of CT, ECG and carotid ultrasound results to stratify follow-up urgency. Other patient groups are at increased risk of stroke independent of the classical risk stratification systems. These include patients with multiple TIAs within a short period and patients with a probable or proven cardioembolic source.
Table 8.2.5
The ABCD2 TIA risk score
From 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;369:283-92 with permission.
Antiplatelet therapy
Following CT scanning that excludes ICH, aspirin should be commenced at a dose of 300 mg and maintained at 75–150 mg per day in patients with TIAs or minor ischaemic strokes. It 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 risk of bleeding complications but there was a significantly increased rate of withdrawal of patients from the combination arm due to side effects from 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 prevention of vascular events but at greater expense. The combination of aspirin and clopidogrel 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%. The benefit of surgery may extend to lesser grades of stenosis down to 50% in selected patients. The patient’s baseline neurological state, co-morbidities and operative mortality and morbidity rate also need to be assessed when considering surgery. The recent CREST trial compared carotid artery stenting (CAS) with endarterectomy (CEA). It revealed slightly superior stroke prevention for CEA in symptomatic patients. In patients with significant co-morbidities, CAS remains an option.
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 a recent 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 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 or MRI scan should be performed to exclude ICH prior to commencing aspirin. Aspirin should be withheld for at least 24 hours in patients treated with thrombolytics.
Thrombolysis
As the most important factor in ischaemic stroke outcome is vessel re-opening, thrombolytic agents are seen as having an important place in the management of acute ischaemic stroke. The evidence on which thrombolysis was originally approved was the NINDs study of 1996. In that 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 (NNT)=8). In the thrombolysis group, there was a significant increase in symptomatic 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. More recently, three other phase III trials of thrombolysis have been published. The DIAS-2 study was described previously in this chapter. ECASS 3 studied IV tPA versus placebo in ischaemic stroke patients 3–4.5 hours from symptom onset. It had a similar design to NINDS but with additional exclusions of patients aged>80, those with severe stroke (NIHSS>25) or acute ischaemic change on plain CT greater than a third of the MCA territory or a history of previous stroke and diabetes. It found a modest but significant improvement in full or very good neurological recovery (Modified Rankin Score [MRS] 0–1), NNT 14. The outcome for full to good neurological recovery (MRS 0–2) was not significantly improved. The risk of a major symptomatic ICH complicating treatment was 5%. The IST-3 trial studied the open label use of IV tPA versus placebo in ischaemic stroke patients from 0 to 6 hours post-onset in whom the treating physician was uncertain if tPA was clearly indicated or not. Over 3000 patients were enrolled over 10 years. The primary outcome of good neurological function at 6 months (Oxford Handicap Score 0–2) was not significantly improved by tPA. There was an excess of early deaths within 7 days in the tPA group but, by 6 months, this was similar in both groups. Symptomatic ICH rate was 7%. The conclusions that can be inferred from these results have been a matter of considerable debate.
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 centres in accordance with strict guidelines, the complication rate for acute stroke patients can be similar to that achieved in trials. The evidence would also strongly suggest that better outcomes are associated with earlier treatment using current treatment guidelines. The percentage of acute ischaemic stroke patients fulfilling the eligibility criteria and receiving thrombolytic treatment is still relatively low. Importantly, protocol violations are associated with an increased risk of poor outcomes, particularly due to haemorrhage. Stroke guidelines in Australia currently recommend the use of tPA if it can be administered in suitable patients up to 4.5 hours post-onset, although every effort should be made to commence treatment as soon as possible.
Patients receiving tPA must be managed in an high dependency type setting. Any deterioration in clinical state, headache or vomiting should instigate cessation of tPA and urgent CT scan. ICH associated with tPA is managed with attention to ABCDs, reversal of thrombolysis according to local protocols and neurosurgical and ICU involvement as required.
Trials of IV thrombolysis are ongoing with the aims of identifying the best agent, identifying patients most likely to benefit from reperfusion therapy, reducing the risk of symptomatic ICH and extending the time window for treatment. As already discussed, this is particularly through the use of advanced imaging modalities, such as CT perfusion and diffusion/perfusion MRI.
Interventional techniques
Occlusions of the internal carotid and proximal middle cerebral arteries have relatively low rates of recanalization with intravenous tPA. Hence a number of interventional therapies are being investigated either as primary therapy or as a rescue technique post-IV tPA and reperfusion failure. These interventional techniques involve the use of clot retrieval devices and/or intra-arterial thrombolysis and are only available in highly specialized centres. The time window of benefit from interventional therapy may be longer than with IV thrombolysis and may be considered in cases of acute ischaemic stroke due to large vessel occlusion where thrombolysis is contraindicated.
Basilar artery thrombosis has a very poor outcome with conservative management. Case series suggest improved outcomes with interventional techniques, which may be indicated up to 12 hours post-symptom onset.
Anticoagulation
Therapeutic anticoagulation with heparin or clexane is associated with increased risk of haemorrhagic transformation in acute ischaemic stroke. Stroke due to endocarditis has a particularly high risk of this complication. Anticoagulation following acute ischaemic stroke should not be commenced in the ED. In cases of stroke due to cardioembolism, the timing and manner of anticoagulation should be determined by stroke physicians.
Neuroprotection
A range of neuroprotective agents has 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 a vascular imaging modality to detect a significant carotid artery stenosis that may be appropriate for urgent surgery. 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. These are termed malignant MCA infarcts. Along with standard measures for managing raised ICP, there may be a place for early decompressive craniotomy in selected cases. Intensive care and neurosurgical consultation may be required.
Intracerebral haemorrhage
Primary ICH is most commonly caused by long-standing hypertension-induced small vessel disease. Hypertensive haemorrhage tends to occur in characteristic locations, such as the basal ganglia, thalamus and cerebellum. Berry aneurysms most commonly arise around the circle of Willis, hence ICH due to aneurysmal rupture is often located around this area. Secondary ICH may occur into an underlying lesion, such as a tumour or infarct, and clinical deterioration may result – so-called symptomatic ICH – but this is not always the case.
The clinical presentation of primary ICH is typical of sudden onset of a neurological deficit with associated headache, collapse/transient loss of consciousness, hypertension and vomiting. However, clinical features alone are unable to differentiate ICH from infarction, hence the requirement for brain imaging to confirm the diagnosis. Both CT and MRI (using gradient echo sequences) are equivalent in the detection of ICH.
Treatment
Primary ICH is a medical emergency with a high mortality (between 35 and 50%), with half of these deaths occurring in the first 2 days. There is also a very high risk of dependency. Haematomas can expand rapidly and there is a significant risk of early neurological deterioration and increasing intracranial pressure. General measures as for TIAs and ischaemic stroke should be initiated, in particular attention to airway and ventilatory support. Treatment of raised ICP in a setting of ICH involves a range of modalities similar to those used in head trauma. These include elevation of the head of the bed, analgesia, sedation, an osmotic diuretic, such as mannitol, and hypertonic saline, hyperventilation, drainage of CSF via ventricular catheter and neuromuscular paralysis.
Current consensus guidelines in ICH recommend cautious and controlled lowering of a persistently raised systolic blood pressure>180–200 mmHg or mean arterial pressure (MAP)>130–150 following specialist consultation. Recommended agents include rapidly titratable intravenous drugs, such as sodium nitroprusside, labetolol 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 in blood pressure. The results of the SCAST trial, as mentioned previously, may alter this recommendation; however, the outcome of more aggressive blood pressure reduction in ICH is still being evaluated. The INTERACT trial of intensive BP reduction within 6 hours of symptom onset showed a reduction in haematoma growth. The effect on clinical outcomes is being studied in the INTERACT 2 trial. Treatment should be individualized and take place in consultation with stroke/neurosurgery/intensive care specialists. Sudden falls in blood pressure and hypotension should be avoided as they may aggravate cerebral ischaemia in the setting of raised ICP, which is often associated with ICH.
Use of recombinant Factor VIIa is not recommended. Steroids are also not indicated in ICH. Anticonvulsant prophylaxis is common practice.
Management of ICH associated with anticoagulation or thrombolysis is a matter of urgency and should be done in consultation with a haematologist and a neurosurgeon. Depending on the clinical situation, agents such as protamine sulphate, vitamin K, prothrombin complex concentrate, fresh frozen plasma (FFP) and tranexamic acid may be indicated. Factor VIIa normalizes the INR rapidly, but with a greater potential for thromboembolism. Platelets should be considered if the patient is on antiplatelet therapy.
Surgical management
Surgical management of ICH depends on the location, cause, neurological deficit and overall clinical state. Early neurosurgical consultation should be obtained. High-level evidence for improved outcomes following drainage of supratentorial haematomas by craniotomy is lacking, but the procedure may be indicated in selected patients, particularly in those with lobar clots within 1 cm of the surface. In patients with deep haemorrhages, craniotomy is generally not recommended.
External ventricular drainage devices (EVDs) may be indicated if hydrocephalus develops.
The presence of a cerebellar haematoma is a particular indication for surgery, with a potential for a good neurological recovery. A variety of other techniques, such as minimally invasive haematoma evacuation, are under investigation.
Controversies
Thrombolysis is a therapy which may improve neurological outcome in patients with ischaemic stroke when given within 4.5 hours of onset. Problematic issues include the small number of patients who currently present within the time window for treatment; delays in ED assessment and obtaining an expertly reported CT, particularly after hours; identification in the ED of subgroups with higher risk of haemorrhagic complications or lesser treatment benefit; the significant rate of stroke misdiagnosis, with the subsequent potential for unnecessary exposure to a high-risk therapy and the large number of contraindications to thrombolysis. Additionally, protocol violations can increase the risk of a poor outcome.
Advances in neuroimaging, particularly diffusion/perfusion MRI and perfusion CT/CTA, show promise for improved selection of patients likely to benefit from thrombolytic therapy. The optimal imaging strategy remains unclear.
The place of interventional therapies in acute ischaemic stroke is the subject of intense research. They have the potential to improve outcome by prolonging the treatment window, increased recanalization rates in large vessel occlusions and reducing haemorrhagic complications. A number of clot retrieval devices are being evaluated as is intra-arterial thrombolysis.
The place of dabigatran in AF/stroke prevention. Although uptake in the community has been rapid, more time is needed to see whether industry sponsored trials of efficacy translate into real world benefits.
The follow-up investigation and management of patients presenting to emergency departments with TIA is moving increasingly to an outpatient model of care. The optimum method of risk stratification and patient selection for this approach has yet to be conclusively determined.
Treatment of hypertension associated with stroke. Antihypertensive therapy is rarely necessary and recent studies indicate this should not be routinely instituted in the acute phase. Therapy should be considered in patients with persistent very high pressures and intracranial haemorrhage in consultation with treating specialist teams. Ongoing studies are evaluating the value of intensive reduction of high blood pressures in the setting of ICH. Hypertension may require treatment in the setting of thrombolytic therapy in accordance with local protocols.
Neuroprotective therapies continue to be evaluated but, at this stage, cannot be recommended outside a clinical trial.
Further reading
1. Barber PA, Demchuk AM, Zhang J, Buchan AM for the ASPECTS Study Group. The validity and reliability of a novel quantitative CT score in predicting outcome in hyperacute stroke prior to thrombolytic therapy. Lancet. 2000;355:1670–1674.
2. Brott TG, Hobson RW, Howard G, et al. for the CREST investigators Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363:11–23.
3. CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomised placebo controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke. Lancet. 1997;349:1641–1649.
4. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–1151.
5. Hacke W, Furlan AJ, Al-Rawi Y, et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion–diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2009;8:141–150.
6. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke (ECASS 3). N Engl J Med. 2008;359:1317–1329.
7. 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.
8. Kidwell CS, Chalela JA, Saver JL, et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. J Am Med Assoc. 2004;292:1823–1834.
9. National Stroke Foundation. Clinical guidelines for stroke management. Melbourne, 2010.
10. North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET). Beneficial effects of carotid endarterectomy in symptomatic patients with high grade carotid stenosis. N Engl J Med. 1991;325:445–453.
11. Nor AM, Davis J, Sen B, et al. The recognition of stroke in the emergency room (ROSIER) scale: development and validation of a stroke recognition instrument. Lancet Neurol. 2005;4:727–734.
12. Rothwell PM, Giles MF, Chandratheva A, et al on behalf of the EXPRESS study investigators. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007;370:1432–1442.
13. Sandset EC, Bath PM, Boysen G, et al. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet. 2011;377:741–750.
14. Sanders LM, Srikanth VK, Jolley DJ, et al. Monash transient ischemic attack triaging treatment Safety of a transient ischemic attack mechanism-based outpatient model of care. Stroke. 2012;43:2936–2941.
15. Spence JD, Pelz D, Veith FJ. Asymptomatic carotid stenosis. Identifying patients at high enough risk to warrant endarterectomy or stenting Stroke. 2011;42:1–3.
16. The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT). Lancet. 2006;367:1665–1673.
17. The IST 3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012;379:2352–2363.
18. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (NINDS). Tissue plasminogen activator for acute ischaemic stroke. N Engl J Med. 1995;333:1581–1587.
8.3 Subarachnoid haemorrhage
Pamela Rosengarten
Essentials
1 The diagnosis of subarachnoid haemorrhage (SAH) requires a high index of suspicion.
2 Up to 50% of patients with SAH experience a warning leak – the sentinel haemorrhage – in the hours to days prior to the major bleed.
3 Risk of re-bleeding is maximal in first 2–12 hours and is associated with a poor prognosis and high mortality.
4 Severe sudden headache is the primary clinical feature.
5 Brain CT scan without contrast is the initial investigation of choice.
6 A negative CT scan for SAH should be followed by lumbar puncture and examination of the cerebrospinal fluid.
7 Patients with SAH require urgent neurosurgical referral and management.
8 Early definitive isolation and occlusion of the aneurysm reduces early complications and improves outcome.
9 Endovascular treatment is the treatment of choice in most cases.
Introduction
Patients with headache account for approximately 1% of all emergency department (ED) visits and, of these, 1–4% have a final diagnosis of subarachnoid haemorrhage (SAH). Early accurate diagnosis of aneurysmal SAH is imperative, as early occlusion of the aneurysm has been shown to reduce early complications of re-bleeding and vasospasm and improve outcome.
Epidemiology and pathology
SAH is the presence of extravasated blood within the subarachnoid space. The incidence in Australia is approximately 10 cases per 100 000 patient-years, but is significantly higher (around 20 per 100 000) in Japan and Finland, for reasons that are unclear. Although incidence increases with age, about half of those affected are aged under 55, the condition being most common in the 45–64 age group.
The most common cause of SAH is head trauma which is dealt with elsewhere in this book. Non-traumatic or spontaneous SAH results from rupture of a cerebral aneurysm in approximately 85% of cases, non-aneurysmal perimesencephalic haemorrhage in 10% and the remaining 5% from other rare causes including rupture of mycotic aneurysms, intracranial arterial dissection, arteriovenous malformations, vasculitis, central venous thrombosis, bleeding diatheses, tumours and drugs, such as cocaine, amphetamines and anticoagulants.
Aneurysms
Intracranial aneurysms are not congenital. Rather, they develop during the course of life. An estimate of the frequency for an adult without risk factors is 2.3%, with the proportion increasing with age. Most aneurysms will never rupture, but the risk increases with size. Paradoxically, as the vast majority of aneurysms are small, most aneurysms that rupture are small. An aneurysm of the posterior circulation is more likely to rupture than one of comparable size in the anterior circulation.
Risk factors can be divided into those that are modifiable and those that are not. Modifiable risk factors include cigarette smoking, hypertension, sympathomimetic drug use (e.g. cocaine) and excessive alcohol intake. Non-modifiable factors include history of previous aneurysmal SAH, a family history of first-degree relatives with SAH, inherited connective tissue disorders (particularly polycystic kidney disease and neurofibromatosis), sickle cell disease and α1-antitrypsin deficiency.
Non-aneurysmal perimesencephalic haemorrhage
This type of SAH is defined by the characteristic distribution of blood in the cisterns around the midbrain in combination with normal angiographic studies. It usually carries a relatively benign prognosis. A small proportion of patients with this distribution of blood may have a ruptured aneurysm of a vertebral or basilar artery.
Clinical features
History
The history is critical to the diagnosis of SAH:
Headache is the principal presenting symptom, being present in up to 95% of patients with SAH and being the solitary symptom in up to 40% of patients. It is typically severe, of sudden onset, almost instantaneously reaching peak intensity and often being the worst headache ever experienced. Approximately 25% of patients presenting with sudden severe headache will have SAH.
Up to 50% of patients experience a warning leak (sentinel haemorrhage) in the hours to weeks before the major bleed. This headache may be mild, generalized or localized, of variable duration, resolve spontaneously within minutes to hours or last several days and usually responds to analgesic therapy. It does, however, tend to develop abruptly and differ in quality from other headaches that the patient may have previously experienced. Hence a patient’s worst or first headache is suggestive of SAH.
Upper neck pain or stiffness is common.
One-third of patients will develop SAH during strenuous exercise, e.g. bending or lifting, whereas in the remaining two-thirds it will occur during sleep or routine daily activities.
Nausea and vomiting are present in 75% of patients.
Brief or continuing loss of consciousness occurs in the majority of patients. Severe headache is usually experienced when the patient regains consciousness, although a brief episode of excruciating headache may occur prior to losing consciousness.
Seizures occur in up to 20% of patients and, when associated with a typical headache, are a strong indicator of SAH, even if the patient is neurologically normal when assessed.
Prodromal symptoms, particularly third cranial nerve with pupillary dilatation and sixth cranial nerve palsies are uncommon, but may suggest the presence and location of a progressively enlarging unruptured aneurysm.
No clinical feature can reliably identify SAH.
Examination
There is a wide spectrum of clinical presentations, the level of consciousness and clinical signs being dependent on the site and extent of the haemorrhage:
On ED presentation, two-thirds of patients have impaired level of consciousness – 50% with coma. Consciousness may improve or deteriorate. An acute confusional state can occur which may be mistaken for a psychological problem.
Signs of meningism, photophobia and neck stiffness, are present in 75% of patients, but may take several hours to develop and may be absent in the deeply unconscious. Absence of neck stiffness does not exclude SAH. Fever may also be present.
Focal neurological signs are present in up to 25% of patients and are secondary to associated intracranial haemorrhage, cerebral vasospasm, local compression of a cranial nerve by the aneurysm (e.g. oculomotor nerve palsy by posterior communicating aneurysm or bilateral lower limb weakness due to anterior communicating aneurysm) or raised intracranial pressure (sixth-nerve palsy).
Ophthalmological examination may reveal unilateral or bilateral subhyaloid haemorrhages or papilloedema.
Systemic features associated with SAH include severe hypertension, hypoxia and acute ECG changes that may mimic acute myocardial infarction.
A small proportion of patients present in cardiac arrest. Resuscitation attempts are vital, as half of survivors regain independent function.
Patients are categorized into clinical grades from I to V, according to their conscious state and neurological deficit. Two grading schemes, that of Hunt and Hess and that of the World Federation of Neurosurgeons, which is preferred, are depicted in Table 8.3.1. The higher the score, the worse the prognosis.
Table 8.3.1
Clinical grading schemes for patients with SAH
WFNS: World Federation of Neurosurgeons; GCS: Glasgow coma score. Reproduced with permission from Sawin PD, Loftus CM. Diagnosis of spontaneous subarachnoid hemorrhage. Am Fam Phys 1997;55:145–56.
Differential diagnosis
Important differential diagnoses include benign thunderclap headache (40%), migraine, cluster headache, headache associated with sexual exertion, vascular headaches of stroke, intracranial haemorrhage, venous thrombosis and arterial dissection, meningitis, encephalitis, acute hydrocephalus, intracranial tumour and intracranial hypotension.
Clinical investigations
Imaging
Computed tomography (CT)
Non-contrast brain CT scan is the initial investigation of choice. In the first 24 hours after haemorrhage it can demonstrate the presence of subarachnoid blood in more than 95% of cases (Fig. 8.3.1). The sensitivity, however, decreases with time owing to the rapid clearance of blood, with only 80% of scans positive at 3 days and 50% positive at 1 week. CT will also demonstrate the site and extent of the haemorrhage, indicate the possible location of the aneurysm and demonstrate the presence of hydrocephalus and other pathological changes.
FIG. 8.3.1 Non-contrast head CT scan demonstrating widespread subarachnoid and intraventricular blood.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) with FLAIR (fluid attenuated inversion recovery) proton density, diffusion weighted imaging and gradient echo sequences is reliable in demonstrating early SAH and is superior to CT in detecting extravasated blood in the days (up to 40 days) following haemorrhage. Availability and logistical considerations, including longer procedure time, make MRI impractical for use in the initial diagnostic work-up of SAH, but it may be considered in patients who present late.
CT angiography
CT angiography (CTA) is the preferred angiographic technique once SAH has been identified. Compared to catheter angiography, it has a sensitivity of 98% for cerebral aneurysms, is readily available and has a lower complication rate. It should be performed as soon as the diagnosis is made. Where diagnosis has been made by CT, CTA should preferably be performed while the patient is still in the scanner. CTA is usually of sufficient quality to allow planning of endovascular or neurosurgical interventions. It is important to note that small aneurysms<3 mm may not reliably be detected on CTA and so further investigations may be warranted in CTA-negative SAH.
A CT/CTA approach has been suggested as an alternate diagnostic strategy to CT/LP (lumbar puncture) in the diagnosis of SAH. However, this approach focuses on identifying an aneurysm, rather than the presence of intracranial haemorrhage. The consequence of this strategy may be that the aneurysm detected is an incidental finding, as aneurysms are known to occur in about 2.5% of the normal population. This would then result in unnecessary investigation and treatment of an asymptomatic aneurysm and so is currently not supported.
Cerebral angiography
Cerebral angiography is the gold standard for confirming the presence of an aneurysm, its location and the presence of vasospasm and was previously the preferred angiographic test. It is not, however, without risk. Neurological complications occur in ≈1.8% of cases, with re-rupture of an aneurysm reported in 2–3%. It is also less available than CTA. These factors have seen it become less favoured and used in selected cases only.
Magnetic resonance angiography
MR angiography is currently useful as a screening tool for the diagnosis of intracranial aneurysms in patients at increased risk.
Further imaging when no cause for SAH is found
In patients where SAH is present and no cause is found, then the distribution of extravasated blood on the CT scan should be reviewed. If this conforms to the perimesencephalic distribution of non-aneurysmal haemorrhage, then no further investigations may be warranted. If, however, an aneurysmal pattern of haemorrhage is present, then a second CTA is recommended as occasionally an aneurysm may have gone undetected on the original test.
Lumbar puncture
Lumbar puncture is necessary when there is clinical suspicion of SAH, the CT scan is negative, equivocal or technically inadequate and no mass lesion or signs of raised intracranial pressure are found. In about 3–5% of patients with SAH, the CT scan will be normal. Although it has been suggested that a negative CT scan performed in the first 6 hours following headache onset is sufficient to exclude a diagnosis of SAH, evidence is inadequate to support this practice and so cannot be recommended to replace a CT/LP strategy.
The diagnosis of SAH, then, is dependent on the finding of red blood cells not due to traumatic tap or red blood cell breakdown products within the CSF. Lumbar puncture should be delayed for at least 6 and preferably 12 hours after symptom onset to allow bilirubin to be formed from cell breakdown in SAH. Detection of bilirubin and xanthochromia is the only reliable method of distinguishing SAH from a traumatic tap. Proceeding to angiographic studies in every patient with bloodstained CSF would be expected to identify an incidental finding of a small unruptured aneurysm in about 2%.
It is important to measure the opening pressure when performing a lumbar puncture, as CSF pressure may be elevated in SAH or in other conditions, such as intracranial venous thrombosis or pseudotumour cerebri, or low in spontaneous intracranial hypotension.
Xanthochromia, the yellow discoloration of CSF caused by the haemoglobin breakdown products oxyhaemoglobin and bilirubin due to lysis of red blood cells, is generally agreed to be the primary criterion for diagnosis of SAH and differentiates between SAH and traumatic tap. It is usually present within 6 hours of SAH and has been demonstrated in all patients with SAH between 12 hours and 2 weeks following the haemorrhage. Xanthochromia is not reliably detected by visual examination of centrifuged CSF. Spectrophotometric analysis of CSF for bilirubin is considered the most sensitive means of detecting xanthochromia.
Controversy exists as to the optimal timing of lumbar puncture. Early lumbar puncture within 12 hours may have negative or equivocal CSF findings, whereas delayed lumbar puncture may result in an increased risk of early re-bleeding as well as having practical implications for the ED. In general, at least 6–12 hours should have elapsed between the onset of headache and lumbar puncture. Although detection of xanthochromia is indicative of SAH, it does not entirely rule out traumatic lumbar puncture and can occur in extremely bloody taps (>12 000 RBC/mL) or where the lumbar puncture has been repeated after an initial traumatic tap.
Other studies of the CSF, such as three tube cell counts, D-dimer assay and detection of erythrophages, have been found to be inconsistent in differentiating SAH from traumatic tap.
General investigations
General investigations to be performed include full blood examination, erythrocyte sedimentation rate, urea, electrolytes including magnesium, blood glucose, coagulation screen, chest X-ray and 12-lead ECG. ECG changes are frequently present and include ST and T-wave changes which may mimic ischaemia, QRS and QT prolongation and arrhythmias. Cardiac biomarkers, including troponin, may also be elevated.
Complications
Early complications
Re-bleeding: up to 15% within hours of the initial haemorrhage and, overall, 40% of patients re-bleed within the first 4 weeks if there is no intervention. Re-bleeding is associated with 60% mortality and half of the survivors remain disabled.
Subdural haematoma or large intracerebral haematoma can be life threatening and require immediate drainage. Similarly, a large intracerebral haematoma may be contributing to the poor clinical condition and warrant drainage simultaneously with treatment of the aneurysm.
Global cerebral ischaemia: irreversible brain damage resulting from haemorrhage at the time of aneurysm rupture. This is probably secondary to a marked rise in intracranial pressure resulting in inadequate cerebral perfusion.
Cerebral vasospasm: clinically significant vasospasm occurs in approximately 20% of patients with SAH and is a major cause of death and morbidity. It tends to occur between days 3 and 15 after SAH, with a peak incidence at days 6–8. Vasospasm causes ischaemia or infarction and should be suspected in any patient who suffers a deterioration in their neurological status or develops neurological deficits. The best predictor of vasospasm is the amount of blood seen on the initial CT scan.
Hydrocephalus occurs in approximately 20% of patients with SAH. It can occur within 24 hours of haemorrhage and should be suspected in any patient who suffers a deterioration in mentation or conscious state, particularly if associated with slowed pupillary responses.
Seizures.
Fluid and electrolyte disturbances: patients with SAH may develop hyponatraemia and hypovolaemia secondary to excessive natriuresis (cerebral salt wasting) or, alternatively, may develop a syndrome of inappropriate ADH (SIADH).
Hyperglycaemia and hyperthermia, both of which are associated with a poor outcome.
Medical complications include pulmonary oedema, cardiogenic or neurogenic (23%), cardiac arrhythmias (35%), sepsis, venous thromboembolism and respiratory failure.
Late complications
Late re-bleeding, from a new aneurysm or regrowth of the treated aneurysm, is estimated at ≈1.3% in 4 years for coiling and ≈2–3% in 10 years for surgical clipping.
Anosmia: up to 30%.
Epilepsy: 5–7%.
Cognitive deficits and psychosocial dysfunction are common even in those who make a good recovery; 60% of patients report personality change.
Treatment
The management of SAH requires general supportive measures, particularly airway protection and blood pressure control, as well as specific management of the ruptured aneurysm and the complications of aneurysmal haemorrhage.
General measures
Stabilization of the unconscious patient, with particular attention to the airway. Endotracheal intubation with oxygenation and ventilation will be required in patients with higher-grade (4–5) SAH.
Close observation of Glasgow coma scale (GCS) and vital signs.
In all patients, maintain oxygenation and circulation ensuring adequate (euvolaemic) blood volume.
Analgesia, using reversible narcotic analgesic agents, sedation and antiemetics as required. Ensure bed rest with minimal stimulation. Avoid aspirin and non-steroidal analgesic agents (NSAIDs).
Blood pressure control: blood pressure levels are often of the order of 150/90 immediately following SAH and, in most patients, can be adequately controlled by sedation and analgesia. Normotensive levels extending to mild to moderately hypertensive levels, especially in patients with pre-existing hypertension, are acceptable. Antihypertensive therapy should be reserved for patients with severe (mean arterial pressure>130 mmHg) hypertension or where there is evidence of progressive end-organ dysfunction and short-acting antihypertensive agents (e.g. esmolol or nitroprusside) and intensive haemodynamic monitoring should be employed.
Fever should be regulated to maintain normothermia which is associated with improved functional outcome.
Seizures should be treated as they occur. The routine use of long-term prophylactic phenytoin is controversial and has been linked with unfavourable functional and cognitive outcomes.
Correct electrolyte imbalances. Hyponatraemia of excessive natriuresis must be differentiated from that of SIADH. Hypovolaemia is to be avoided.
Effective glucose control, importantly avoiding hyper- and hypoglycaemia.
Venous thromboembolism prophylaxis, initially with compressive devices and later with subcutaneous heparin following treatment of the aneurysm.
Treatment of hydrocephalus by ventricular drainage may be required.
Specific treatment
Prevention of re-bleeding
Obliteration of the ruptured aneurysm by endovascular coiling or surgical clipping should be performed as early as possible to prevent re-bleeding, remove clot, reduce the incidence of early complications and improve outcomes.
Endovascular occlusion, achieved by placing detachable coils in aneurysms under radiological guidance (coiling), has largely replaced surgical occlusion as the method of choice for prevention of re-bleeding in suitable cases. The method of treatment, however, depends on anatomical considerations, as aneurysms are not equally amenable to this option. In aneurysms that are suitable to treatment by either modality, 4-year outcome has been demonstrated to be better with coiling, although there are higher aneurysm recurrence and re-bleeding rates.
Surgical clipping is now a second-line option for most patients. It is usually done early – within 3 days, and preferably within 24 hours.
Antifibrinolytic agents, including ε-aminocaproic acid, which inhibit clot lysis, reduce the incidence of re-bleeding after initial aneurysmal rupture. Short-term therapy (<72 hours) may be indicated in patients without medical contraindications who have an unavoidable delay in obliteration of the aneurysm and a significant risk of re-bleeding. Although not affecting clinical outcome, their use has been associated with an increase in deep venous thrombosis but not pulmonary embolism.
Prevention of delayed cerebral ischaemia
Cerebral ischaemia is often gradual in onset and involves the territory of more than one cerebral artery. Peak frequency is at 5–14 days after SAH. Nimodipine, a calcium channel antagonist, improves clinical outcome in SAH, with a relative risk reduction of 18% and an absolute risk reduction of 5.1%. The current standard regimen is nimodipine 60 mg orally every 4 hours for 3 weeks. It should be commenced within 48 hours of haemorrhage.
Other treatments including magnesium sulphate, the statins and antiplatelet agents have not been demonstrated to improve clinical outcomes.
There are no definitive treatments for delayed cerebral ischaemia, although improving cerebral perfusion by maintenance of euvolaemia and induced hypertension is recommended where blood pressure and cardiac status permit. In vasospasm unresponsive to medical management, emergency cerebral angiography with intra-arterial vasodilator infusion or transluminal balloon angioplasty may be considered where focal vessel narrowing is demonstrated.
Prognosis
SAH has a 40–60% mortality rate from the initial haemorrhage, with up to one-third of survivors having a significant neurological deficit. The most important prognostic factor is the clinical condition at the time of presentation, with coma and major neurological deficits generally being associated with a poor prognosis. Survival rates have been reported at 70% for grade I, 60% for grade II, 50% for grade III, 40% for grade IV and 10% for grade V SAH.
It is worth noting, however, that survival without brain damage is possible even after respiratory arrest. Even patients who make a good recovery may suffer cognitive and psychosocial dysfunction.
Aneurysm screening in patients who have survived aneurysmal SAH is advocated, as these patients are at increased risk of new or recurrent aneurysmal bleeds.
Incidental unruptured aneurysms
If an unruptured aneurysm is found incidentally, it raises the dilemma of the risk–benefit rationale between intervention and conservative management. Factors taken into account include age, aneurysm size and location, gender, country, co-morbidity and family history. Such patients should be referred to a neurosurgical service for advice and counselling.
Conclusion
Clinical suspicion of the diagnosis of SAH gained from a history of sudden, severe or atypical headache demands a full investigation, including brain CT scan and, if necessary, lumbar puncture. Once SAH has been diagnosed, urgent neurosurgical referral and management are required.
Controversies
The timing of lumbar puncture (LP) following a negative CT scan for SAH.
Non-contrast CT without LP within first 6 hours of headache and CT/CTA as diagnostic strategies for SAH.
Vascular imaging for patients with a negative CT scan and negative CSF is indicated in those with ambiguous test results, those at high risk for SAH and patients presenting after more than 2 weeks.
Prophylactic anticonvulsant therapy for patients with SAH.
Follow up for patients after coiling.
Further reading
1. Arora S, et al. Evaluating the sensitivity of visual xanthochromia in patients with subarachnoid hemorrhage. J Emerg Med. 2010;39:13–16.
2. Connolly Jr ES, Rabinstein AA, Carhuapoma JR, et al on behalf of the American Heart Association Stroke Council. Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Nursing, Council on Cardiovascular Surgery and Anesthesia, and Council on Clinical Cardiology Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43:1711–1737.
3. Dorhout Mees SM, Rinkel GJE, Vermeulen M, van Gijn J. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 4:CD000277.
4. Edlow JA. What are the unintended consequences of changing the diagnostic paradigm for subarachnoid hemorrhage after brain computed computed tomography angiography in place of lumbar puncture? Acad Emerg Med. 2010;17:991–995.
5. Lai L, Morgan MK. Incidence of subarachnoid hameorrhage: an Australian national hospital morbidity database analysis. J Neurosci. 2012;19:733–739.
6. Lysack JT, et al. Asymptomatic unruptured intracranial aneurysms: approach to screening and treatment. Can Fam Phys. 2008;54:1535–1538.
7. Mark DG, MD, Hung Y, Offerman SR, et al. for the Kaiser Permanente CREST Network Investigators. Nontraumatic subarachnoid hemorrhage in the setting of negative cranial computed tomography results: external validation of a clinical and imaging prediction rule. Ann Emerg Med ePub; 2012 [Accessed Nov. 2012].
8. McCormack RF, Hutson AA. Can computed tomography angiography of the brain replace lumbar puncture in the evaluation of acute onset headache after negative non contrast cranial computed tomography scan? Acad Emerg Med. 2010;17:444–451.
9. Naval NS, Stevens RD, Mirski MA. Controversies in the management of subarachnoid haemorrhage. Crit Care Med. 2006;34:511–524.
10. Suarez JI, Tarr RW, Selman WR. Current concepts: aneurysmal subarachnoid haemorrhage. N Engl Med J. 2006;354:387–398.
11. van Gijn J, Kerr RS, Rinkel GJE. Subarachoid haemorrhage. Lancet. 2007;369:306–318.
8.4 Altered conscious state
Ruth Hew
Essentials
1 For clinical purposes, the ability of the individual to respond appropriately to environmental stimuli provides a quantifiable definition of consciousness. The Glasgow coma score is used to quantify conscious state and monitor progress.
2 The causes of altered conscious state can be divided pathophysiologically into structural and metabolic insults.
3 A thorough history and examination is the key to guiding investigation choice and identifying the cause of the primary insult. Management is directed towards resuscitation, specific correction of the primary pathology and minimization of secondary injury.
4 Bedside blood glucose measurement is essential and may be life saving.
Introduction
Consciousness is variously termed lucidness, orientation, awakeness and mentation in the context of patients in the emergency department (ED). None of these terms is a comprehensive definition of consciousness. Neither does the Glasgow coma scale (GCS) (Table 8.4.1), commonly used but developed for head-injured patients in a time when computed tomography (CT) scanning was not yet available, truly measure what we as clinicians mean by conscious state. Ultimately, consciousness is an amalgam of alertness, orientation and clarity of cognition or mentation. Of note, isolated absence or derangement of cognition and mentation (e.g. caused by dementia or psychiatric illness or both) does not result in the clinical entity of altered conscious state. Both these clinical presentations are considered elsewhere. In the same way, the lack of orientation in and of itself does not constitute a clinical alteration in conscious state.
Table 8.4.1
The Glasgow coma scale
The GCS is scored between 3 and 15, 3 being the worst and 15 the best. It is composed of three parameters: best eye response, best verbal response, best motor response, as given below
Best eye response (score out of 4)
1 – No eye opening
2 – Eye opening to pain
3 – Eye opening to verbal command
4 – Eyes open spontaneously
Best verbal response (score out of 5)
1 – No verbal response
2 – Incomprehensible sounds
3 – Inappropriate words
4 – Confused
5 – Orientated
Best motor response (score out of 6)
1 – No motor response
2 – Extension to pain
3 – Flexion to pain
4 – Withdrawal from pain
5 – Localizing pain
6 – Obeys commands
In the clinical context, an alteration in conscious state requires a drop in alertness and ‘awakeness’. This drop in alertness may result in a corresponding loss of orientation and/or a clouding of cognition, thereby altering a patient’s response to environmental stimuli or provocation. The reverse, an increase in alertness, could also be considered an alteration in conscious state but, in practice, is most often due to pharmacological agents or a mood elevating psychiatric illness and is beyond the scope of this discussion.
Pathophysiology
The level of consciousness describes the rousability of the individual, whereas the content of consciousness may be assessed in terms of the appropriateness of the individual’s response. Broadly speaking, the first is a brainstem function and the second is an attribute of the forebrain.
The physical portions of the brain involved in consciousness consist of the ascending arousal system that begins with monoaminergic cell groups in the brainstem and culminates in extensive diffuse cortical projections throughout the cerebrum. En route there is input and modulation from both thalamic and hypothalamic nuclei, as well as basal forebrain cell groups.
The integration of the brainstem and the forebrain is illustrated by individuals who have an isolated pontine injury. They remain awake, but the intact forebrain is unable to interact with the external world, hence the aptly named ‘locked-in syndrome’. At the other end of the spectrum are individuals in a persistent vegetative state who, in spite of extensive forebrain impairment, appear awake but totally lack the content of consciousness. These clinical extremes emphasize the important role of the brainstem in modulating motor and sensory systems through its descending pathways and regulating the wakefulness of the forebrain through its ascending pathways.
Differential diagnosis
Given the pathophysiology, the causes of an altered conscious state are myriad and include any cause of insult or injury either directly or indirectly to the brain (Table 8.4.2). Direct injury resulting in structural insults could be traumatic or non-traumatic, e.g. subdural haemorrhage, stroke. Indirect injury could encompass any change in the metabolic and chemical milieu of the brain resulting in a depression of neuronal function, e.g. sepsis, hyper- or hypoglycaemia, drug ingestion.
Table 8.4.2
Causes of Alteration in Conscious State
STRUCTURAL INSULTS
Supratentorial
Haematoma
epidural
subdural
Cerebral tumour
Cerebral aneurysm
Haemorrhagic CVA
Infratentorial
Cerebellar AVM
Pontine haemorrhage
Brainstem tumour
METABOLIC INSULTS
Loss of substrate
Hypoxia
Hypoglycaemia
Global ischaemia
Shock
hypovolaemia
cardiogenic
Focal ischaemia
TIA/CVA
vasculitis
DERANGEMENT OF NORMAL PHYSIOLOGY
Hypo- or hypernatraemia
Hyperglycaemia/hyperosmolarity
Hypercalcaemia
Hypermagnesaemia
Addisonian crisis
Seizures
status epilepticus
post-ictal
post-concussive
Hypo- or hyperthyroidism
Co-factor deficiency
Metastatic malignancy
Psychiatric illness
Dementia
TOXINS
Drugs
alcohol
illicit
prescription
Endotoxins
subarachnoid blood
liver failure
renal failure
Sepsis
systemic
Focal
meningitis
encephalitis
Environmental
hypothermia/heat exhaustion
altitude illness/decompression
envenomations
Structural insults, commonly focal intracranial lesions that exert direct or indirect pressure on the brainstem and the more caudal portions of the ascending arousal system, tend to produce lateralizing neurological signs that can assist in pinpointing the level of the lesion. As there is little space in and around the brainstem, any extrinsic or intrinsic compression will rapidly progress through coma to death, unless the pressure on the brainstem is relieved surgically or pharmacologically.
Metabolic insults, commonly due to systemic pathology that affects primarily the forebrain (although direct depression of the brainstem may also occur), seldom result in lateralizing signs. The appropriate treatment is the correction of the underlying metabolic impairment. Naturally, as in all clinical practice, there are no absolute distinctions. Uncorrected, any of the metabolic causes can eventually cause cerebral oedema and herniation, leading thence to brainstem compression with lateralizing signs, coma and death.
Clinical assessment
In approaching a patient with an altered conscious state, the initial imperatives are to ensure the safety of the airway, the breathing and the circulation and to determine the cause for the alteration with a view to correcting the rapidly reversible causes and offering supportive care while working through the remainder. To this end, assessment and management must proceed concurrently. As in other time critical situations, the primary and secondary survey approach often proves useful, seeking to identify and correct the primary insult while preventing or minimizing secondary injury, such as hypoxia, acidosis and raised intracranial pressure.
Primary survey and resuscitation
An assessment of the airway, breathing and circulation of the patient is urgent to ensure that life-saving measures, such as airway and ventilation support, can be instituted. Initially, supplemental oxygen and non-invasive monitoring should be applied and attention paid to the absolute value and trends in GCS and vital signs. Normotension should be the goal of blood pressure monitoring and this may require inotropic or antihypertensive support.
Early endotracheal intubation may be required if the GCS is less than 8 or ventilatory effort is inadequate. Mechanical ventilation to maintain a pCO2 of 30–35 mmHg may assist in correcting underlying acidosis and reducing intracranial pressure; however, over-correction may itself be detrimental. Accurate end-tidal CO2 monitoring correlated to arterial pCO2 is required. In the setting of trauma, spinal precautions should be maintained until any possibility of trauma is excluded or until clearance of the spine can be obtained.
As hypoglycaemia is an easily identified and corrected cause of altered conscious state, an early bedside glucose determination is vital.
In certain patient populations, pinpoint pupils and a depressed respiratory response may suggest a diagnosis of opiate toxicity and the administration of naloxone as a diagnostic and therapeutic tool. Often this has already been attempted by the pre-hospital services where the practice of intranasal naloxone administration has significantly reduced the risk of needlestick injuries. Although the adverse reactions to naloxone in initial doses is small, the greater risk is in the unmasking of the proconvulsant or proarrhythmic effects of other drugs ingested or injected in combination with opioids. Thus, naloxone should not be given unless clinically indicated. There is also the potential of introducing diagnostic bias as a percentage of non-opioid users also appear to respond clinically to naloxone. The routine use of the ‘coma cocktail’ of 50% dextrose, naloxone and thiamine intravenously is no longer advocated.
Secondary survey
Following initial assessment and resuscitation, it is important to complete the assessment by obtaining a full history, conducting a full examination and performing any adjunctive investigations. This will assist in identifying the cause of the condition and planning further management.
History
This is often difficult with an obtunded or confused patient and may need to rely heavily on ancillary sources, such as first responders, carers, primary physicians, medical records and patient alert identification.
It is crucial to establish the events leading up to the presentation with specific questioning about prodromal events (e.g. ingestions, IV drug usage, trauma, underlying illness, medications, allergies) and associated seizures and abnormal movements. For example, the presence or absence of a headache and its onset and duration might aid in the clinical diagnosis of a subarachnoid haemorrhage and a history of head injury with loss of consciousness would increase the likelihood of an extra-axial intracranial collection. Patients who are taking anticoagulants also have an increased risk of intracranial haemorrhage with minimal trauma. Patients with a history of hepatic failure may require specific treatment for hepatic encephalopathy.
In the elderly, dementia, itself a progressive illness, may be exacerbated by delirium caused by an acute illness and often, only a careful, corroborated history from care providers and the passage of time will allow the two to be distinguished. Often, the most helpful portion of the history lies in ascertaining the patient’s usual pattern of behaviour and the degree and time course of any changes that have occurred. In these patients, it is important to remember that dementia as a cause of altered conscious state is a diagnosis of exclusion.
Examination
A general physical examination, bearing in mind the various differential diagnoses, is very important. In the absence of adequate history, a thorough physical examination may offer the only pointers to initial treatment. Vital signs may suggest sepsis or other causes of shock. A keen sense of smell might detect fetor hepaticus or the sweet breath of ketosis. A bitter almond scent is pathognomonic of cyanide poisoning. Of note, alteration of consciousness can be attributed to alcoholic intoxication only by the process of exclusion. Thus the characteristic odour of alcoholic liquor is indicative but cannot be presumed to be diagnostic. A bedside blood glucose determination is mandatory as deficits are easily correctable.
Neurological examination must be as comprehensive as possible. There are several obstacles to this. Initial resuscitation measures, such as endotracheal intubation, will reduce the ability of the patient to cooperate with the examination and language difficulties will be accentuated as the neurological examination is strongly language orientated. Thus patients who do not share a common language with clinicians and those with dysphasia may be disadvantaged. Also, sensory modalities are difficult to assess in patients with impaired mentation, although these deficits are often paralleled by deficits in the motor system.
The aim of the neurological examination is, primarily, to differentiate structural and non-structural causes; secondly, to identify groups of signs that may indicate specific diagnoses, such as meningitis; and, finally, to pinpoint the location of any structural lesion. Therefore, emphasis needs to be placed on signs of trauma, tone, reflexes, pupillary responses and eye signs, as well as serial calculation of GCS. Circumstances permitting, some or all of the neurological examination should be documented before the patient receives neuromuscular paralysing agents.
Signs of trauma need to be documented and spinal precautions taken as indicated. Palpation of the soft tissues and bones of the skull may detect deformity or bruising and a haemotympanum may herald a fracture of the base of the skull.
Hypotonia is common in acute neurological deficits. Specific examination of anal sphincter tone will uncover spinal cord compromise and is crucial in trauma patients who have a depressed level of consciousness. An upgoing Babinski response is indicative of pyramidal pathology and asymmetry of the peripheral limb reflexes may help to ‘side’ a lesion. Conversely, heightened tone in the neck muscles (neck stiffness) may indicate meningitis or subarachnoid haemorrhage.
Pupillary responses and eye signs may also be useful to differentiate metabolic and structural insults and, more importantly, to detect incipient uncal herniation. Intact oculocephalic reflexes and preservation of the ‘doll’s eyes’ response indicates an intact medial longitudinal fasciculus and, by default, an intact brainstem, suggesting a metabolic cause for coma. There are four pairs of nuclei governing ocular movements and they are spread between the superior and inferior midbrain and the pons. The pattern of ocular movement dysfunction can be used to pinpoint the site of a brainstem lesion (Table 8.4.3). Likewise, specific testing of the oculovestibular reflex and the cranial nerve examination can be used to locate precisely a brainstem lesion but is of limited use in the emergency setting except as a predictor of herniation (Tables 8.4.3 and 8.4.4).
Table 8.4.3
Ocular responses to cold caloric testing of the oculovestibular reflex
Table 8.4.4
Patterns of dysfunction in various parameters determined by the site of the structural or metabolic insult
More generally, skin examination may reveal needle tracks suggestive of drug use, envenomation bite marks or a meningococcal rash. Mucosal changes, such as cyanosis or the cherry-red glow of carbon monoxide poisoning, can be diagnostic. Cardiac monitoring and cardiovascular examination should identify rhythm disturbances, the murmurs of endocarditis and valvular disease or evidence of shock from myocardial ischaemia or infarction. Respiratory patterns may aid in identifying the site of the lesion (see Table 8.4.4). Abdominal examination may detect organomegaly, ascites, bruits or pulsatile masses.
Collections of physical signs, particularly into toxidromes, such as those due to anticholinergic or serotoninergic drugs, should be sought as these are not uncommon causes of alterations in conscious state with or without psychiatric symptoms. Further information on toxidromes can be found in the relevant chapters in this text.
Clinical investigations
Given the breadth of differential diagnoses, these must be guided by the preceding history and examination and their timing dictated by the resuscitation imperatives. The following is an extensive list of possible investigations but there is no suggestion that they should all be performed in every patient with an altered conscious state without due consideration of the patient’s context and condition. A comprehensive history and thorough examination are key to the appropriate choice of investigations.
Haematology
A full blood examination may reveal anaemia, immunocompromise, thrombocytopaenia, inflammation or infection, but is rarely diagnostically specific. In the setting of trauma, a bedside haemoglobin determination can direct immediate blood-product replacement. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are non-specific acute-phase reactants and single determinants are not initially useful, although they may later be followed to monitor resolution of the illness or response to therapy. Coagulation profiles are particularly useful in haematological and liver disease or if patients are taking anticoagulants, such as warfarin, and should lower the threshold for radiological imaging of the brain.
Biochemistry
Serum electrolyte levels aid in the differentiation of the various hypo- and hyper-elemental causes of coma. Electrolyte imbalances may also be secondary to the causative insult and may not need specific correction. In hypotensive patients, a high to normal sodium and low potassium suggests primary or secondary Addisonian crisis.
Cardiac markers, liver, renal and thyroid function tests may confirm focal organ dysfunction. The last may not always be readily available, but hypothyroidism should be considered in the hypothermic patient and hyperthyroidism in the presence of tremor and tachyarrhythmias.
Serum glucose provides confirmation of bedside testing. Serum lactate determinations may reveal a metabolic acidosis and reflect the degree of tissue hypoxia which, again, may be primary or secondary. Creatinine kinase and myoglobinuria are useful to determine the presence and extent of rhabdomyolysis and to predict the likelihood of requiring dialysis. Serum and urine osmolarity may be useful in toxic ingestions, such as ethylene glycol, and in other hyperosmolar states.
Blood gas analysis may give important information regarding acid–base balance, a useful marker of severity of disease and, along with the anion gap and the serum electrolytes, can help distinguish between the various types and causes of acidosis and alkalosis. Knowledge of the partial pressures of oxygen and carbon dioxide is vital to resuscitative efforts.
Microbiology
Sepsis is a major metabolic cause of conscious state alteration and may present with no localizing symptoms or signs, especially in the elderly. In this case, blood cultures – preferably multiple sets obtained before antibiotic therapy – may be the only means of isolating the causative organism. Naturally, system-specific specimens, such as sputum, urine and cerebrospinal fluid, should be collected when clinically indicated. A bedside dipstick of the urine sample can provide valuable information to begin initial treatment. Although as a rule specimens should be obtained prior to therapy, in suspected meningitis or encephalitis, the administration of antibiotics or antiviral agents should not be delayed while a lumbar puncture/CT scan is performed.
Specific laboratory testing
Based on information from the history and examination, specific drug assays and urine screens may be indicated. These may include over-the-counter or prescribed medications, such as paracetamol, lithium or theophylline, or drugs of addiction, such as amphetamine or opiates. Routine urine drug screens are of very limited overall value and no help to emergency management.
Venom detection kits can be used in specific clinical situations and evidence of systemic envenomation can be screened for with other tests, such as coagulation profiles and creatinine kinase.
Imaging
Intracranial imaging is best achieved with a plain CT of the head which, if normal and concern regarding intracranial pathology persists, may be followed by a contrast-enhanced scan or magnetic resonance imaging (MRI). The latter has a higher sensitivity for encephalitis and cerebral vasculitis, although it may not always be easily accessible from the ED. Also, the technical constraints of MRI require a stable patient. Emergency CT angiography has a role in the delineation of cerebral aneurysms and interventional angiography can provide therapeutic options, particularly in a patient who is progressing towards herniation. A normal CT scan does not completely exclude treatable intracranial infection or subarachnoid haemorrhage. Therefore, depending upon the patient’s conscious state and the level of clinical suspicion, a lumbar puncture may further assist with diagnosis. However, it must be emphasized that, in suspected intracranial infection, an obtunded patient should be treated empirically with appropriate antiviral agents and antibiotics and the lumbar puncture deferred till the risk of herniation is minimized.
A chest X-ray may reveal primary infection or malignancy. In a patient with an altered conscious state and any suspicion of head trauma, a full cervical spine series is mandatory. Inadequate plain films should be supplemented by CT imaging of the cervical spine, as allowed by resuscitation imperatives while spinal immobilization is maintained. Imaging of the rest of the spine and the pelvis should be guided by clinical assessment.
Other tests
The 12-lead ECG can highlight rate and rhythm disturbances. Specific changes, such as the U wave of hypokalaemia, the J wave of hypothermia and focal infarction and ischaemic patterns, serve to confirm and offer pointers to the cause of the conscious state alteration. It is worth noting that intracranial bleeding, such as subarachnoid haemorrhage, can be associated with an ischaemic-looking ECG. Care is required in cases of depressed level of consciousness with ECG changes, as the use of thrombolysis or anticoagulation based on the ECG in the presence of intracranial bleeding may well be fatal.
Treatment
Management, by necessity, is governed by assessment findings, projected differential diagnoses and the patient’s response to initial management. The algorithm in Figure 8.4.1 is aimed at correcting immediate life-threatening pathology and then identifying and treating reversible structural and metabolic causes. Treatment of specific causes is addressed elsewhere in this text.
FIG. 8.4.1 Altered conscious state: management algorithm.
General measures
The priorities of ED management are the avoidance of hypoxia, hypotension, hyperthermia and hyperglycaemia, the maintenance of normovolaemia and cerebral perfusion and the minimization of any increase in intracranial pressure. It is important to normalize vital parameters and strict monitoring of the same with invasive measures as required.
For monitoring of blood pressure and pCO2, an arterial line is required in these patients. Strict attention to fluid replacement and the need to monitor end-organ perfusion also dictates the need for a urinary catheter. This can also be used to monitor core temperature. The target temperature should be 35°C to avoid hyperthermia.
With regards to drugs required for the management of the airway and ventilation, propofol is a powerful, fast-acting, short-duration sedative that provides potentially neuroprotective effects through decreases in peripheral vascular tension. However, review of multiple small trials and datasets do not suggest any overall long-term mortality benefits of propofol over the opiate class in the management of sedation and ventilation of the traumatic brain-injured patient. It is important to provide analgesia and sedation as the absence of these will result in physiological stimulation and increase intracranial pressure. Optimization of ventilation is useful to reduce hypoxia and, while neuromuscular paralytic agents may assist in the endeavour, it is important to document as much of the neurological examination as possible prior to paralysing the patient.
Intracranial pressure management
The use of osmotic diuretics may also assist in reducing intracranial pressure but the choice of agent has become more controversial with the introduction of hypertonic saline. There are no class I studies comparing the efficacy of either mannitol (0.5 g/kg) or hypertonic saline (5 mL/kg of 3% saline) with placebo for intracranial pressure reduction, but class II and class III evidence suggests that both may be effective with mannitol potentially being the less effective. Such agents should be used only in consultation with the receiving neurosurgical team due to their potential for additional haemodynamic compromise and secondary neurological embarrassment.
Disposition
Patients with continuing altered consciousness should be admitted to a hospital with the range of services and clinical disciplines to manage the primary diagnosis. This may require stabilization prior to transfer and transport, sometimes over long distances. The exigencies of transfer may also dictate some of the initial management choices. The level of care required will depend on the state of the patient on presentation and their subsequent response to treatment. Patient wishes, premorbid status and prognosis may also temper treatment choices and pathways.
Prognosis
Discussion of prognosis is difficult, as it depends on the cause and patient-specific factors. Effective cerebral resuscitation with optimal oxygenation and minimization of intracerebral hypercarbia and acidosis will promote the best recovery potential while addressing the underlying disease process. Prognosis is naturally dependent on the degree of irreversible cellular damage and the ability to correct the primary insult while minimizing secondary brain injury.
Controversies
The optimal degree of induced hypercapnoea in the management of the patient with an altered conscious state.
The role and choice of osmotic diuretics in the management of acute elevations in intracranial pressure.
The interplay between patient and family wishes, premorbid status, prognosis and medical futility in the decision-making process determining management pathways and dispostion.
Further reading
1. Adamides AA, Winter CD, Lewis PM, et al. Current controversies in the management of patient with severe traumatic brain injury. Aust NZ J Surg. 2006;76:163–174.
2. Banks CJ, Furyk JS. Hypertonic saline use in the emergency department. Emerg Med Australas. 2008;20:294–305.
3. Casaletto JJ. Is salt, vitamin or endocrinopathy causing this encephalopathy? A review of endocrine and metabolic causes of altered level of consciousness. Emerg Med Clin N Am. 2010;28:633–662.
4. Hoffman JR, Schringer DL, Luo JS. The empiric use of naloxone in patients with altered mental status: a reappraisal. Ann Emerg Med. 1991;20:246–252.
5. Jantzen JAH. Prevention and treatment of intracranial hypertension. Best Pract Res Clin Anaesthesiol. 2007;21:517–538.
6. Kaplan JL, Marsi JA, Calabro JJ, et al. Double-blind randomised study of nalmefene and naloxone in emergency department patients with narcotic overdose. Ann Emerg Med. 1999;34:42–50.
7. Kelly AM, Kerr D, Dietze P, et al. A randomised trial of intranasal versus intramuscular naloxone in prehospital treatment for suspected opioid overdose. Med J Assoc. 2005;182:24–27.
8. Meyer MJ, Megyes J, Meythaler J, et al. Acute management of acquired brain injury part II: An evidence-based review of pharmacological interventions. Brain Injury. 2010;24:706–721.
9. Schreckinger M, Marion DW. Contemporary management of traumatic intracranial hypertension: Is there a role for therapeutic hypothermia? Neurocrit Care. 2009;11:427–436.
10. Sporer KA, Firstone J, Issacs SM. Out-of-hospital treatment of opioid overdose in an urban setting. Acad Emerg Med. 1996;3:660–667.
11. Teasdale G, Jennett B. Assessment of coma and impaired consciousness: a practical scale. Lancet. 1974;2:81–84.
12. White H, Cook D, Venkatesh B. The use of hypertonic saline for treating intracranial hypertension after traumatic brain injury. Anesth Analg. 2006;102:1836–1846.
8.5 Seizures
Garry J Wilkes
Essentials
1 Up to 10% of the population will have at least one seizure in their lifetime, but only 1–3% will develop epilepsy.
2 The management of an acute episode is directed at rapid control of seizures, identification of precipitating factors and prevention/correction of complications.
3 Investigation of first seizures should be directed by history and clinical findings. Routine laboratory and radiological investigations are not warranted for uncomplicated first seizures with full recovery.
4 Persistent confusion should not be assumed to be due to a post-ictal state until other causes have been excluded.
5 Benzodiazepines and phenytoin are the principal anticonvulsant agents for acute seizures.
6 Status epilepticus and eclampsia are severe life threats. Management plans for these conditions should be developed in advance.
7 Pseudoseizures are important to distinguish from neurogenic seizures in order to prevent inadvertent harm to patients and allow appropriate psychotherapeutic treatment.
8 Management of drug-related seizures (including those related to alcohol) includes measures to reduce drug absorption and enhance elimination. Specific therapy is available for only a few agents. Phenytoin is usually ineffective in the management of alcohol and drug-related seizures.
9 Severe head injuries are associated with an increased incidence of post-traumatic epilepsy, half of which will be manifest in the first year. Phenytoin is effective as prophylaxis for the first week only.
10 Patients with epilepsy should be encouraged to have ongoing care.
Introduction
The terms ‘seizure’,’convulsion’ and ‘fit’ are often used both interchangeably and incorrectly. A seizure is an episode of abnormal neurological function caused by an abnormal electrical discharge of brain neurons. The seizure is also referred to as an ictus or ictal period. A convulsion is an episode of excessive and abnormal motor activity. Seizures can occur without convulsions and convulsions can be caused by other conditions. The term ‘fit’ is best avoided in medical terminology, but is a useful term for non-medical personnel.
Epidemiology
Seizures are common. It has been estimated that up to 10% of the population will have at least one seizure in their lifetime and 1–3% of the population will develop epilepsy. A single seizure may be a reaction to an underlying disorder, part of an established epileptic disorder or an isolated event with no associated pathology. The challenge is rapidly to identify and treat life-threatening conditions as well as to identify benign conditions that require no further investigation or treatment.
Diagnosis of epilepsy requires at least two unprovoked seizures more than 24 hours apart. An episode of status epilepticus is considered a single seizure. Simple febrile and neonatal seizures are usually excluded from this definition.
Classification
Epileptic seizures can be classified into partial and generalized. Partial epileptic seizures are further classified into simple partial (preserved consciousness) and complex partial seizures. Either may secondarily become generalized.
Generalized seizures can be divided into convulsive and non-convulsive types. Convulsive seizures are generalized tonic–clonic (grand mal) seizures. Non-convulsive generalized seizures include absence seizures (previously termed petit mal), myoclonic, tonic and atonic seizures. Epilepsy and epileptic syndromes are also classified as focal or generalized. Each disorder can be further classified, according to its relationship to aetiological or predisposing factors, into symptomatic or cryptogenic. The term ‘idiopathic’ is now discouraged. Seizures can also be classified as provoked (acute symptomatic) or unprovoked (cryptogenic or remote symptomatic).
Different seizure types are associated with differing aetiological and prognostic factors. The details of the classification systems are not as important in emergency medicine as the concept of recognizing the different seizure types and being aware of the accepted terminology when discussing and referring cases.
Management principles
Given the high frequency of this condition in emergency departments (EDs), it is important to have an evidenced-based management strategy formulated in advance. The main management concepts are:
Altered mental state should be thoroughly assessed and not assumed to be due to a post-ictal state.
Patients with known epilepsy who have recovered completely from a typical seizure require little further investigation. If they remain obtunded or have atypical features, they must be fully evaluated, e.g. biochemical analysis, computed tomography (CT) scan, etc.
Patients with epilepsy should be encouraged to seek continuing care.
Patients at risk of recurrent seizures should be advised about situations of increased personal risk, such as driving, operating power machinery or swimming alone.
Differential diagnosis
Conditions such as syncope may be accompanied by myoclonic activity and are important to distinguish from true seizures. Migraine, transient ischaemic attacks, hyperventilation episodes and vertigo are all important conditions to consider in the differential diagnosis. Pseudoseizures will be discussed below.
First seizures
A generalized convulsion is a dramatic event. Patients and those accompanying them will often be frightened, anxious and concerned, not only for the acute event but for what it may signify. A diagnosis of epilepsy may profoundly influence occupation, social activities, ability to drive a car and long-term health. It is therefore vital the diagnosis is correct and explained fully to the patient and relatives.
Clinical features
The first and most important task is to determine whether a seizure has occurred. As the majority have ceased, the diagnosis is made primarily on history. Patients will not remember seizures other than simple partial seizures and the reports of witnesses may be unreliable or inconsistent. With the exception of partial seizures, generalized seizures are not accompanied by an aura. Most seizures last less than 2 minutes, are associated with impaired consciousness, loss of memory for the event, purposeless movements and a period of post-ictal confusion. Although witnesses may grossly overestimate the duration, prolonged seizures, those occurring in association with a strong emotional event and those with full recall of events should be regarded with suspicion. Similarly, motor activity that is coordinated and not bilateral (such as side-to-side head movements, pelvic thrusting, directed violence and movement that changes in response to external cues) are less likely to be true seizures.
ED assessment is aimed at identifying associated conditions and treatable causes of seizures. The aetiology of seizures can be classified into five groups on this basis:
Acute symptomatic: occurring in association with a known central nervous system insult. Causes of this large, important group are listed in Table 8.5.1.
Remote symptomatic: occurring without provocation in a patient with a previous history (>1 week prior) of central nervous system insult known to be associated with an increased risk of seizures, e.g. encephalopathy, meningitis, head trauma or stroke.
Progressive encephalopathy: occurring in association with a progressive neurological disease, e.g. neurodegenerative diseases, neurocutaneous syndromes and malignancies not in remission.
Febrile: patients whose sole provocation is fever. This is almost exclusively confined to children and, as such, is beyond the scope of this book.
Cryptogenic (previously ‘idiopathic’): patients without a precipitating central nervous system insult. This is probably the most common group, however, this classification is by exclusion of the other causes.
Table 8.5.1
Acute symptomatic causes of seizures
Hypoxia
Hypoglycaemia
Head trauma
Meningitis and encephalitis, including HIV disease
Metabolic, including hyponatraemia, hypocalcaemia, hyperthyroidism, uraemia and eclampsia
Drug overdose, including alcohol, tricyclics, theophylline, cocaine, amphetamine and isoniazid
Drug withdrawal, including alcohol, benzodiazepines, narcotics, cocaine and anticonvulsants
Cerebral tumour or stroke
A careful history is needed to decide whether this is part of an ongoing process or an isolated event. Patients may not recall previous events, may not recognize their significance or may even avoid reporting previous episodes for fear of being labelled ‘epileptic’, with the associated consequences. Particular attention should be paid to any history of unexplained injuries, especially when they occur during blackouts or during sleep. A history of childhood seizures, isolated myoclonic jerks and a positive family history increases the likelihood of epilepsy.
A full physical and neurological examination is mandatory. Evidence of alcohol and drug ingestion and head trauma is particularly important. A comprehensive medication history will include agents known to reduce seizure threshold in susceptible individuals, e.g. tramadol and selective serotonin reuptake inhibitors. A careful mental state examination in seemingly alert patients may reveal evidence of a resolving post-ictal state or underlying encephalopathy. Patients not fully alert should never be assumed simply to be in a post-ictal state until other causes are excluded. Evidence of underlying causes includes fever, nuchal rigidity (meningitis), cardiac murmurs (endocarditis), needle tracks, evidence of chronic liver disease, dysmorphic features and marks such as café-au-lait spots (neurofibromatosis). Complications, such as tongue biting, broken teeth and peripheral injuries, are not uncommon in generalized seizures. Stress fractures can occur, particularly in the elderly. Posterior dislocation of the shoulder is uncommon but significant and easily overlooked.
Clinical investigations
Although it is common practice to order a variety of tests following an uncomplicated seizure, these are rarely of benefit in the fully recovered patient. Elevated neutrophil counts in blood and CSF may be seen as a result of a generalized seizure in the absence of an infectious disorder. Electrolyte abnormalities may cause seizures but are unlikely to be the cause if the patient has recovered. Serum prolactin level 20–60 minutes post-seizure may be helpful if the diagnosis is in doubt. An abnormal neurological examination, features of meningitis, encephalitis or subarachnoid haemorrhage are indications for cranial CT scan and lumbar puncture.
Imaging
There are no clear guidelines to the routine need for or urgency of neuroimaging following a single uncomplicated seizure. Patients with focal neurological signs, those who do not recover to a normal examination and those with a history of head trauma or intracranial pathology should all undergo cranial CT as soon as possible. The dilemma arises in patients with complete recovery and no focal signs. The incidence of abnormalities on CT in this group of patients is less than 1%. The decision as to whether to and when to scan patients in this group will be determined largely by local factors. Magnetic resonance imaging (MRI) is more sensitive than CT for infarcts, tumours, inflammatory lesions and vascular lesions but availability may be limited.
Electroencephalography
Electroencephalography (EEG) at the time of a seizure will make a definitive diagnosis. It is not usually performed in the acute setting except when non-convulsive activity is suspected. Typically, an EEG is obtained electively on an outpatient basis, when it may still indicate an underlying focus of activity and may be able to detect specific conditions.
Treatment
Once a diagnosis of first seizure is made and intercurrent conditions are excluded or treated, the patient may be discharged home. It must be stressed to the patient that a diagnosis of epilepsy has not been made but is being considered. When the suspicion is reasonable, the patient should be given the same precautionary advice as epileptic patients with regard to driving and other activities that may place them or others at risk.
The planning of investigation and follow up for patients suspected of having a first seizure is best done in conjunction with a neurology service to ensure appropriate investigations are completed in a timely fashion. Generally, an inter-ictal EEG and contrast CT and/or MRI are completed prior to review.
Status epilepticus
Epidemiology and pathophysiology
Status epilepticus may be defined as ‘two or more seizures without full recovery of consciousness between seizures, or recurrent epileptic seizures for more than 30 minutes’.
Status epilepticus accounts for 1–8% of all hospital admissions for epilepsy, 3.5% of admissions to neurological intensive care and 0.13% of all visits to a university hospital ED. It is more common at the extremes of age, with over 50% of all cases occurring in children and a disproportionately high incidence in those over 60 years of age. Status epilepticus is also more frequent in the mentally handicapped and in those with structural cerebral pathology, especially of the frontal lobes. Four to 16% of adults and 10–25% of children with known epilepsy will have at least one episode of status epilepticus. Notwithstanding, status epilepticus occurs most commonly in patients with no previous history of epilepsy.
Many compensatory physiological changes accompany seizures. As duration increases these mechanisms begin to fail, with an increased risk of permanent damage. Brain damage resulting from prolonged status epilepticus is believed to be caused by excitatory amino acid neurotransmitters, such as glutamate and aspartate, leading to influx of calcium into neuronal cytoplasm and an osmotolytic cell destruction. Continuing seizure activity itself contributes to neuronal damage, which is further exacerbated by hypoxia, hypoglycaemia, lactic acidosis and hyperpyrexia. The longer an episode of status epilepticus continues, the more refractory to treatment it becomes and the more likely it is to result in permanent neuronal damage. Mortality increases from 2.7% with seizure duration under 1 hour to 32% with duration beyond this. Generalized convulsive status epilepticus is therefore a medical emergency.
Treatment
Treatment of status epilepticus is along the same lines as the resuscitation of all seriously ill patients. Management is in a resuscitation area with attention to:
rapid stabilization of airway, breathing and circulation
termination of seizure activity (clinical and electrical)
identification and treatment of precipitating and perpetuating factors
identification and treatment of complications.
Each stage of resuscitation is made more difficult by the presence of active convulsions. Do not prise clenched teeth apart to insert an oral airway: a soft nasal airway will suffice. Oxygen should be given and the patient positioned in the left lateral position to minimize the risk of aspiration. Intravenous access is important for drug treatment and fluid resuscitation, but may be difficult in actively seizing patients. Although status epilepticus cannot be diagnosed until seizures have persisted for 30 minutes, patients still seizing on arrival at the ED should be treated with anticonvulsants immediately.
The principal pharmacological agents used are benzodiazepines and phenytoin. Opinions vary regarding the optimal benzodiazepine, with little clinical evidence to support any particular one. Lorazepam is preferred by most neurologists because of prolonged central nervous system action (protective effect for 30–120 minutes). Less fat-soluble than diazepam, it typically takes longer to stop seizures (5–10 minutes) and can cause hypotension. Midazolam is popular among emergency physicians for a variety of purposes. Being water soluble, it is non-irritant and can be administered IM with fairly rapid onset of action (between diazepam and lorazepam). It has a short duration of action (another reason for popularity in emergency medicine) and may require further IV doses or ongoing infusion. Diazepam has previously been popular due to its extreme lipid solubility and rapid brain entry. It typically stops seizures in 1–2 minutes. Preparations are, however, irritant, produce complications with IV extravasation and are unsuitable for IM use. Diazepam can be administered rectally if necessary and this technique can be taught to parents with high-risk children. All benzodiazepines share the disadvantages of respiratory depression, hypotension and short duration of clinical effect.
Phenytoin is usually used as a second-line agent in a dose of 15–20 mg/kg at a rate of no more than 50 mg/min. Rapid administration is associated with bradyarrhythmias and hypotension. The common practice of administering 1 g is inadequate for most adults. The effect of phenytoin does not commence until 40% of the dose has been administered; for this reason, it should be commenced at the same time that IV benzodiazepines are given if it is to be used. Most people on anticonvulsants who present in status epilepticus have negligible drug levels and the side effects from a full loading dose on top of a therapeutic level are minimal. The full loading dose should therefore be given even when the patient is known to be on therapy.
The most common causes of failure to control seizures are:
inadequate antiepileptic drug therapy
failure to initiate maintenance antiepileptic drug therapy
hypoxia, hypotension, cardiorespiratory failure, metabolic disturbance, e.g. hypoglycaemia
failure to identify an underlying cause
failure to recognize medical complications, e.g. hyperpyrexia, hypoglycaemia
misdiagnosis of pseudoseizures.
Causes of failure to regain consciousness following treatment of seizures include the medical consequences of status epilepticus (hypoxia, hypoglycaemia, cerebral oedema, hypotension, hyperpyrexia), sedation from antiepileptic medication, progression of the underlying disease process, non-convulsive status epilepticus and subtle generalized status epilepticus.
When benzodiazepines and phenytoin are ineffective, expert advice should be sought. Drugs that may be used in the control of status epilepticus are summarized in Table 8.5.2. Anaesthetic agents require expert airway control and, in some cases, inotropic support. Management in an intensive care unit is mandatory.
Table 8.5.2
Doses of drugs used in refractory status epilepticus
For all patients with status epilepticus, early consultation with intensive care and neurology services is essential in planning definitive management and disposition.
Non-convulsive seizures
Not all seizures are associated with convulsive activity. Convulsive seizures are generally easy to recognize, whereas non-convulsive seizures are more subtle and often require a high index of suspicion. These types of seizure are an important cause of alterations in behaviour and conscious level and may precede or follow convulsive episodes. Seizures can involve any of the sensory modalities, vertiginous episodes, automatism, autonomic dysfunction or psychic disturbances, including déjà vu and jamais vu experiences. Non-convulsive seizures can easily be confused with migraine, cerebrovascular events or psychiatric conditions. The definitive diagnosis can only be made by EEG during the event.
Non-convulsive seizures may be partial (focal) or generalized. Complex partial seizures and focal seizures account for approximately one-third of all seizures, whereas primary generalized non-convulsive seizures (absence seizures) account for 6%.
Non-convulsive status epilepticus accounts for at least 25% of all cases of status epilepticus and is diagnosed more frequently when actively considered. Absence seizures rarely result in complete unresponsiveness and patients may appear relatively normal to unfamiliar observers. Non-convulsive status epilepticus may precede or follow convulsive seizures and may easily create the perception of a cerebral vascular or psychiatric event. The longest reported episode of absence status is 60 days and that of complex partial status 28 days.
Acute treatment of non-convulsive seizures is the same as for convulsive seizures. An estimated 50% of patients with simple partial seizures have abnormal CT scans. Long-term seizure control uses different agents from those used for convulsive seizures, highlighting the importance of involving a neurological service when planning follow up.
Pseudoseizures
Pseudoseizures or psychogenic seizures are events simulating neurogenic seizures but without the accompanying abnormal neuronal activity. Differentiation from neurogenic seizures may be extremely difficult, even for experienced neurologists. Neurogenic and psychogenic seizures may coexist, making the diagnostic dilemma even more complex. Differentiation will often require video-EEG monitoring, but this facility is not available in the ED and other methods must be used. It is important to recognize pseudoseizures so as to prevent the possible iatrogenic consequences of unnecessary treatment while, at the same time, not withholding treatment from patients with neurogenic seizures.
Pseudoseizures are more common in women, less common after 35 years of age and rare in patients aged over 50. They may be associated with a conversion disorder, malingering, Munchausen syndrome or Munchausen syndrome by proxy.
Pseudoseizures typically last more than 5 minutes, compared to 1–2 minutes for neurogenic seizures. Multiple patterns of seizures tend to occur in individual patients and post-ictal periods are either very brief or absent. Recall of events during what appears to be a generalized convulsive seizure suggests a psychogenic seizure. Extremity movement out of phase from one side to the other and head turning from side to side typify pseudoseizures. Forward pelvic thrusting occurs in 44% of patients with pseudoseizures and is highly suggestive of the diagnosis.
Several manoeuvres are useful in identifying pseudoseizures. Eye opening and arm drop tests are accompanied by avoidance, eyes turning away from the moving examiner and termination of the event when the mouth and nostrils are occluded are characteristic. Simple verbal suggestion and reassurance are also frequently successful.
The most definitive means of identifying pseudoseizures is by ictal EEG or video-EEG monitoring. Unfortunately, this is of little value in the ED. A fall in SpO2 on pulse oximetry and a degree of acidaemia on blood gas analysis occur during neurogenic but not pseudoseizures. Serum prolactin levels rise and peak 15–20 minutes after generalized tonic–clonic seizures and then fall with a half-life of 22 minutes. The levels do not consistently rise with partial seizures and remain normal with pseudoseizures.
Patients with pseudoseizures usually demonstrate resistance to anticonvulsant medication and many will therefore present with therapeutic or supratherapeutic levels. Correct diagnosis will prevent unnecessary and potentially harmful treatment. Doubtful cases should be discussed with a neurology service and arrangements made for emergency EEG.
Once the diagnosis is confirmed, it must be presented in an open and non-threatening manner. Patients often have underlying personal and/or family problems that will need to be addressed. Psychotherapy is effective, but seizures often relapse at times of stress.
Alcohol-related seizures
Alcohol contributes to half of seizures presenting to EDs. Acute toxicity and withdrawal are both associated with an increased incidence of seizures. Alcohol intoxication and chronic alcohol abuse are also associated with increased incidences of intercurrent disease, such as trauma, coagulopathy, falls, assaults and other drug intoxication, all of which further increase the likelihood of seizures. The management of seizures presumed to be alcohol related must include a search for associated disease and other causes.
Benzodiazepines are the principal anticonvulsant agent for acute seizures. These agents are also valuable in the treatment of withdrawal. Phenytoin is ineffective in the control of acute alcohol-related seizures or as a preventative for them.
Drug-related seizures
Seizure activity in the setting of acute drug overdose is an ominous sign associated with greatly increased mortality and morbidity. The most commonly reported are in association with cyclic antidepressants, antihistamines, theophylline, isoniazid and illicit drugs, such as cocaine and amphetamines. The diagnosis and management of these are discussed in the section on toxicology.
Some medications are also associated with lowering seizure threshold in susceptible individuals. Tramadol, in particular, has been associated with new-onset seizures at normal therapeutic doses. A complete medication history is therefore essential.
Post-traumatic seizures
Post-traumatic epilepsy develops in 10–15% of serious head injury survivors. More than half will have their first seizure within 1 year. Risk factors are central parietal injury, dural penetration, hemiplegia, missile wounds and intracerebral haematomas. Early treatment with phenytoin for severe head injuries reduces the incidence of seizures in the first week only.
Seizures and pregnancy
Seizures can occur during pregnancy as part of an established epileptic process, as new seizures or induced by pregnancy. The most significant situations are eclampsia and generalized convulsive status epilepticus. At all times, the management is directed at both mother and baby, with the realization that the best treatment for the baby will relate to optimal maternal care.
In previously diagnosed epileptics, there is an increased risk of seizures during pregnancy of 17%. Anticonvulsant levels are influenced by reduced protein binding, increased drug binding and reduced absorption of varying degrees. The final effect on free drug levels is unpredictable and is most variable around the time of delivery.
Isolated simple seizures place both mother and fetus at increased danger of injury, but are otherwise generally well tolerated. Generalized seizures during labour cause transient fetal hypoxia and bradycardia of uncertain significance. Generalized convulsive status epilepticus is life threatening to both mother and fetus at any stage of pregnancy.
All of the anticonvulsants cross the placenta and are potentially teratogenic. The risk of malformation in children is increased from 3.4% in the general population to 3.7% in epileptic mothers. In general, the types of malformation associated are not drug specific, apart from the increased risk of neural tube defects associated with valproate and carbamazepine. Prenatal screening for such defects is advised in patients who become pregnant while taking these agents. The risk from uncontrolled seizures greatly outweighs the risk from prophylactic medication in patients with good seizure control.
The management of seizures in pregnant patients is along the same lines as for non-pregnant patients. After 20 weeks’ gestation, the patient should have a wedge placed under the right hip to prevent supine hypotension and eclampsia must be considered. Investigation will include an assessment of fetal well-being by heart rate, ultrasound and/or tocography, as indicated. Management and disposition should be decided in consultation with neurology and obstetric services.
Eclampsia is the occurrence of seizures in patients with pregnancy-induced toxaemia occurring after the twentieth week of pregnancy. Toxaemia consists of a triad of hypertension, oedema and proteinuria. One in 300 women with pre-eclampsia progresses to eclampsia. Seizures are typically brief, self-terminating, usually preceded by headache and visual disturbances. They tend to occur without warning. Treatment is directed at controlling the seizures and hypertension and expedient delivery of the baby. Magnesium sulphate is effective in seizure control and is associated with a better outcome for both mother and baby than standard anticonvulsant and antihypertensive therapy.
Management of status epilepticus in pregnancy includes consideration of eclampsia, positioning in the left lateral position and assessment and monitoring of fetal well-being. Urgent control of seizures is essential for both mother and baby. Phenobarbital may reduce the incidence of intraventricular haemorrhage in premature infants and should be considered in place of phenytoin in this circumstance. Early involvement of obstetric and neurology services is essential. Pre-eclampsia and eclampsia are addressed specifically in Chapter 19.7.
Future directions
Non-invasive portable modalities allowing definitive precise diagnosis of seizures in the ED will reduce the need for subsequent investigations in the majority of patients who do not have true epilepsy and permit early focused therapy. Advances in pharmacotherapy and neurosurgical techniques will also improve seizure control with minimal side effects, allowing patients to resume normal activities more effectively. Advances in neurobiology understanding of channels, receptors and genetic expression of proteins will allow correction of underlying defects, removing the need for anticonvulsive therapy.
Controversies
Investigation required for patients with first seizures.
Place of lumbar puncture in the investigation of first seizures.
Role of antipyretics in febrile seizures.
Further reading
1. American College of Emergency Physicians.. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2004;43:605–625.
2. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51:676–685.
3. Brown AF, Wilkes GJ. Emergency department management of status epilepticus. Emerg Med. 1994;6:49–61.
4. Cavasos JE. Epilepsy and seizures.<http://www.eMedicine.com/article/1184846-overview>[Accessed Nov. 2012].
5. Dugan EM, Howell JM. Posttraumatic seizures. Emerg Med Clin N Am. 1994;12:1081–1107.
6. Gates JR, Ramani V, Whalen S, et al. Ictal characteristics of pseudoseizures. Arch Neurol. 1985;42:1183–1187.
7. Hesdorffer DC, Logroscino G, Benn EK, et al. Estimating risk for developing epilepsy: a population-based study in Rochester, Minnestoa. Neurology. 2011;76:23–27.
8. Jagoda A. Nonconvulsive seizures. Emerg Med Clin N Am. 1994;12:963–971.
9. Labate A, Newton MR, et al. Tramadol and new-onset seizures. Med J Aust. 2005;182:42–43.
10. McDonagh TJ, Jelinek GA, Galvin GM. Intramuscular midazolam rapidly terminates seizures in children and adults. Emerg Med. 1992;4:77–81.
11. Riggio S. Psychogenic seizures. Emerg Med Clin N Am. 1994;12:1001–1012.
12. Treiman DM. Electroclinical features of status epilepticus. J Clin Neurophysiol. 1995;12:343–362.
8.6 Syncope and vertigo
Rosslyn Hing
Essentials
1 It is important to distinguish between syncope and true vertigo.
2 The most common cause of syncope is neurally-mediated syncope.
3 A detailed history and physical examination are more useful than extensive investigations.
4 It is essential to identify high-risk patients for the serious potential cardiac causes of syncope so that appropriate treatment can be given.
5 A key diagnostic step is to determine whether a central or peripheral cause of vertigo is more likely.
6 Dynamic manoeuvres may be both diagnostic and therapeutic.
Introduction
Syncope and vertigo are relatively common symptoms. They are often described by patients using the term ‘dizziness’; however, it is essential to differentiate between the two. Syncope and vertigo both represent a significant diagnostic challenge and it is important to risk stratify patients accurately to distinguish between potentially life-threatening and benign causes.
Syncope
Syncope as a presenting symptom represents about 1–1.5% of all emergency department attendances. It is a symptom, not a diagnosis. It is defined as a loss of consciousness induced by the temporarily insufficient flow of blood to the brain. Patients recover spontaneously, without therapeutic intervention or prolonged confusion.
There is no simple test to distinguish between the benign and the potentially life-threatening causes of syncope, but a careful history, examination and bedside investigations can help determine appropriate disposition.
The causes of syncope are summarized in Table 8.6.1. The most common cause in all age groups is neurally-mediated syncope, also known as neurocardiogenic or vasovagal syncope. Orthostatic hypotension and cardiac causes are the next most common.
Table 8.6.1
Aetiology of syncope
Clinical features
Patients with syncope are often completely asymptomatic by the time they arrive at hospital. A thorough history and physical examination is the key to finding the correct cause for the syncope. The history should focus on the patient’s recollection of the preceding and subsequent events, including environmental conditions, physical activity, prodromal symptoms and any intercurrent medical problems. Accounts from eyewitnesses or first responders are also vital. Medications that may impair autonomic reflexes need to be scrutinized and a postural blood pressure measurement performed. Physical examination should concentrate on finding signs of structural heart disease, as well as assessing any subsequent injuries.
Neurally-mediated syncope causes a typical prodrome: patients complain of feeling lightheaded and faint and often describe a blurring or ‘tunnelling’ of their vision. This may be accompanied by other vagally-mediated symptoms, such as nausea or sweating. More pronounced vagal symptoms may include an urge to open their bowels. If patients are unable or unwilling to follow their body’s natural instincts to lie flat, they may collapse to the ground as they lose consciousness. This reflex brings the head level with the heart, resulting in an improvement in cerebral perfusion and a return to consciousness. During this time, the patient may exhibit brief myoclonic movements, which can be mistaken for seizure activity but, in contrast to true epileptic seizures, there are no prolonged post-ictal symptoms. Fatigue is common following syncope.
Orthostatic hypotension occurs when the patient moves from a lying position to a sitting or standing position. If the required autonomic changes fail to compensate adequately, even healthy individuals will experience lightheadedness or blurring of their vision and possibly a loss of consciousness. The most vulnerable people are those with blunted or impaired autonomic reflexes, such as the elderly, those on certain medications (particularly vasodilators, antihypertensive agents and β-blockers) and those who are relatively volume depleted due to heat, excessive fluid losses or inadequate oral intake.
Cardiac syncope is more likely to present with an absent or brief prodrome. Sudden unexplained loss of consciousness should raise suspicion for a cardiac arrhythmia, particularly in the high-risk patient. Both tachycardia and bradycardia can be responsible. A syncopal event while supine is of particular concern and a predictor for a cardiac cause. Those that occur during exertion should prompt a search for structural heart disease, in particular aortic stenosis.
Risk stratification
Most of the published literature on assessment of patients presenting to emergency departments (EDs) with syncope has focused on identifying risk factors for mortality or adverse cardiac outcome. These include a number of scores and clinical decision rules. The OESIL score is based on four high-risk factors identified in a multicentre Italian study aimed at predicting mortality at 1 year. These were age over 65 years, a history of cardiovascular disease (which encompasses ischaemic heart disease, congestive cardiac failure, cerebrovascular disease and peripheral vascular disease), an abnormal ECG (including signs of ischaemia, arrhythmias, prolonged QT interval, AV block or bundle branch block) and absence of the typical prodrome. More recently, the San Francisco Syncope Rule (SFSR) has been developed and validated. In this rule, five factors were used to predict serious short-term and longer-term outcomes. These factors are:
history of congestive cardiac failure
haematocrit<30%
abnormal ECG
patient complaining of shortness of breath
systolic blood pressure<90 mmHg at triage.
Based on these factors, patients with syncope can be divided into high- and low-risk groups as shown in Table 8.6.2. Low-risk patients can be safely discharged for outpatient follow up, but controversy over high-risk patients remains. It is likely that there is a significant proportion of patients in the high-risk group who are actually intermediate risk and, given further evaluation in the ED or a short-stay unit, could also be safely discharged; however, it is more difficult to identify this subset.
Table 8.6.2
Risk stratification for an adverse outcome
|
High risk |
Low risk |
|
Chest pain consistent with IHD |
Age<45 years |
|
History of congestive cardiac failure |
Otherwise healthy |
|
History of ventricular arrhythmias |
Normal ECG |
|
Pacemaker/defibrillator dysfunction |
Normal cardiovascular exam |
|
Abnormal ECG (findings such as prolonged QTc interval, conduction abnormalities, acute ischaemia) |
Prodrome (consistent with neurally-mediated syncope or orthostatic hypotension) |
|
Exertional syncope/valvular heart disease |
|
|
Age>60 years |
IHD: ischaemic heart disease.
Other scores/clinical prediction rules have been developed. Available evidence suggests that while most have good sensitivity, specificity is low resulting in recommendations for hospital admission and/or extensive investigations in a significant number of patients who rule out for serious causes. Work continues to refine clinical decision aids of syncope. Recently, a number of authors have published summaries of the various risk stratification rules, most notably:
Kessler C, et al. The emergency department approach to syncope: evidence-based guidelines and prediction rules. Emerg Med Clin N Am 2010; 28:487–500 and
Serrano LA, et al. Accuracy and quality of clinical decision rules for syncope in the emergency department: a systematic review and meta-analysis. Ann Emerg Med 2010; 56:362-73.
The European Society of Cardiology released its guidelines on the diagnosis and management of syncope in 2009.
Differential diagnosis
Seizures are commonly listed as a cause for syncope. Although they do cause a transient loss of consciousness, the pathophysiology is very different. Post-ictal confusion often helps to differentiate the two; however, urinary incontinence may also occur in syncope. True tonic–clonic activity needs to be distinguished from the brief myoclonic jerks occasionally seen in syncope.
Transient ischaemic attacks (TIAs) are often cited as potential causes for syncope, but this is rare. Only vertebrobasilar territory TIAs can affect the reticular activating system of the brain to cause a loss of consciousness; however, TIA should not be named as a cause for the syncope unless associated with other brainstem signs, such as cranial nerve defects or ataxia.
Syncope may also be the presenting symptom of a potentially life-threatening condition such as pulmonary embolus, subarachnoid haemorrhage, gastrointestinal bleed or aortic aneurysm.
Clinical investigations
The only two mandatory investigations are a 12-lead ECG and blood glucose. These should add enough information to the clinical findings to stratify the patient as high or low risk for an adverse outcome. Research has found that a serum troponin taken at least 4 hours after a syncopal event is not a sensitive predictor of an adverse cardiac outcome.
If pulmonary embolus, subarachnoid haemorrhage, gastrointestinal bleed or aortic aneurysm are suspected, appropriate investigations based on clinical suspicion should be initiated.
Treatment
Treatment depends on the presumptive diagnosis. Those with neurally-mediated syncope require explanation and reassurance only. After ensuring that the vital signs have returned to baseline, their blood glucose and ECG are within normal limits and that they have had something to eat and drink, these patients may be discharged without further investigations.
Patients with orthostatic hypotension often require intravenous fluids and an adequate oral intake to reverse their postural blood pressure changes. Any decision regarding potential changes to chronic medications should ideally include the patient’s primary care/treating doctor.
Patients who are deemed high risk for a cardiac cause need continuous cardiac monitoring for at least 24 hours and admission for further evaluation. This may include echocardiography to identify structural heart problems and to quantify an ejection fraction or electrophysiological studies.
Prognosis
Syncope in a patient with underlying heart disease implies a poor prognosis, with data suggesting that a third will die within a year of the episode. Overall, those with syncope on a background of congestive cardiac failure are at the highest risk for an adverse outcome. In the absence of underlying heart disease, syncope is not associated with excess mortality.
Vertigo
Vertigo is defined as the disabling sensation in which the affected individual feels that they or their surroundings are in a state of constant movement. It has a reported 1-year incidence of 1.4%. Like syncope, it is a symptom not a diagnosis and has as many causes. The difficulty is that, whereas many of the causes of vertigo are benign, it may be a symptom of serious neurological conditions, such as vertebrobasilar stroke.
Aetiology
The causes of vertigo may be divided into peripheral and central as shown in Table 8.6.3.
Table 8.6.3
Aetiology of vertigo
|
Peripheral |
Central |
|
Benign paroxysmal positional vertigo (BPPV) |
Cerebellar haemorrhage and infarction |
|
Vestibular neuritis |
Vertebrobasilar insufficiency |
|
Acute labyrinthitis |
Neoplasms |
|
Ménière’s disease |
Multiple sclerosis |
|
Ototoxicitiy |
Wallenberg’s syndrome (lateral medullary syndrome) |
|
Cerebellopontine angle tumours |
Migrainous vertigo |
|
Post-traumatic vertigo |
Clinical features
It is vital to establish whether the patient is suffering true vertigo, as opposed to pre-syncope, loss of consciousness or mild unsteadiness. It is also necessary to clarify whether they have a sense of continuous motion (vertigo) or whether they feel ‘lightheaded’ or ‘dizzy’.
If the patient feels they are moving in relation to their surroundings, this is termed subjective vertigo, however, if the patient feels that the surroundings are spinning around them, this is termed objective vertigo.
As previously described, vertigo may be central or peripheral in origin. Peripheral vertigo tends to be more intense and associated with nausea, vomiting, diaphoresis and auditory symptoms, such as tinnitus or hearing loss (although hearing loss can rarely occur with vascular insufficiency in the posterior cerebral circulation, as the auditory apparatus is supplied via the anterior inferior cerebellar artery or the posterior inferior cerebellar artery). There may also be a history of ear trauma, barotrauma, ear infection or generalized illness. The onset of the vertigo tends to be subacute, coming on over minutes to hours. Benign paroxysmal positional vertigo (BPPV) has the classic history of position-induced vertigo lasting only seconds. Central vertigo tends to be less severe and associated with neurological symptoms and signs, such as headache, weakness of the limbs, ataxia, incoordination and dysarthria. These symptoms may be the harbinger of more serious causes, such as cerebellar lesions or demyelinating diseases (Table 8.6.4).
Table 8.6.4
Clinical features of vertigo
|
Peripheral |
Central |
|
|
Onset |
Acute |
Gradual |
|
Severity |
Severe |
Less intense |
|
Duration, pattern |
Paroxysmal, intermittent; minutes to days |
Constant; usually weeks to months |
|
Positional |
Yes |
No |
|
Associated nausea |
Frequent |
Infrequent |
|
Nystagmus |
Rotatory – vertical, horizontal |
Vertical |
|
Fatigue of symptoms, signs |
Yes |
No |
|
Hearing loss/tinnitus |
May occur |
Not usually |
|
CNS symptoms, signs |
No |
Usually |
Physical examination concentrates on any positional factors plus a detailed search for neurological signs, in particular, nystagmus. This is the main objective sign of vertigo. Any spontaneous movement of the eyes needs to be noted, including its direction and persistence. Peripheral vertigo tends to produce unidirectional nystagmus with the slow phase towards the affected side. In addition, patients with vestibular nystagmus are often able to suppress it by fixating on a stationary object.
The ‘head impulse’ or ‘head thrust’ test is a simple bedside manoeuvre that can be used to identify the affected labyrinth. With the patient fixating on the examiner’s nose, the examiner holds the patient’s head and performs a few high acceleration but brief turns to either side. The patient’s eyes will automatically move in the opposite direction, in order to maintain visual fixation. The test is positive when this fails to happen and, instead, the patient’s eyes are seen to perform a series of catch up movements, or ‘saccades’ in order to refixate on the examiner’s nose. When the ‘head impulse’ test is positive, the lesion causing the nystagmus is extremely likely to be peripheral. The affected labyrinth is the one in the direction in which the head was moved (see http://www.headimpulse.com/knowledge-center/videos).
Cardiovascular examination should focus on the risk factors for central nervous system thromboembolic events, such as arrhythmias, murmurs and bruits.
Clinical investigations
Most patients who present with vertigo do not need laboratory tests, apart from a blood glucose level. If there is a history of trauma or a space-occupying lesion is suspected, then a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is indicated. An ECG should also be performed to help rule out arrhythmias if differentiation from syncope is problematic.
Dynamic manoeuvres can be both diagnostic and therapeutic. The Dix–Hallpike test can diagnose BPPV. It should not be performed on patients with carotid bruits and patients must be warned that the test may provoke severe symptoms.
Initially, the patient should be seated upright, close enough to the head of the bed so that when they are supine the head will be able to extend back a further 30–45°. To test the right posterior semicircular canal, the head is initially rotated 30–45° to the right. Keeping the head in this position, the patient is quickly brought to the horizontal position with the head placed 30–45° below the level of the bed. A positive test is indicated by rotatory nystagmus towards the affected ear. The test is then repeated on the left side (see http://www.youtube.com/watch?v=cZlXvRlxrRE).
Treatment
Treatment depends on the cause. If BPPV is suspected, the Dix–Hallpike test is performed to identify the affected ear. The Epley manoeuvre or ‘canalith repositioning manoeuvre’ aims to move any unwanted particles out of the semicircular canals and thus ease the symptoms for which they are responsible. The steps of this manoeuvre are:
The patient is seated as for the Dix–Hallpike test with the head turned 45° towards the affected ear.
The patient is brought to the horizontal position with the head hyperextended 30–45° below the bed.
The head is gently rotated 45° towards the midline.
The head is then rotated a further 45° towards the unaffected ear.
The patient rolls onto the shoulder of the unaffected side, at the same time rotating the head a further 45°.
The patient is returned to the sitting position and the head returned to the midline (see http://www.youtube.com/watch?v=59EIKztATiw).
These movements may induce nystagmus in the same direction as that seen during the Dix–Hallpike test. Be aware that nystagmus in the opposite direction indicates an unsuccessful test. The manoeuvre may need to be repeated a few times.
Vestibular neuritis is unilateral and thought to be caused by a viral infection or inflammation. Episodes are acute in onset and may be severe, lasting for days, usually associated with nausea and vomiting. The sense of perpetual movement is present even with the eyes closed and is made worse by movement of the head. Symptomatic treatment, with medications, such as antihistamines, antiemetics and benzodiazepines, is often all that is indicated. If nausea and vomiting are severe, intravenous fluid therapy may be needed. There are some reports of trials using steroids for vestibular neuritis, but this treatment remains unproven.
Acute labyrinthitis may be viral or bacterial in origin. If it is viral, the course and treatment are similar to those of vestibular neuritis. Bacterial labyrinthitis may develop from an otitis media. The key feature here is severe vertigo with hearing loss. Patients are febrile and toxic and require admission for intravenous antibiotics.
Ménière’s disease has the classic triad of vertigo, sensorineural hearing loss and tinnitus. Attacks last from minutes to hours and may recur with increasing frequency as the disease progresses. It is caused by dilatation of the endolymphatic system due to excessive production or problems with reabsorption of the endolymph (endolymphatic hydrops). Medical management traditionally involves salt restriction and diuretics, although a 2006 Cochrane review has questioned the efficacy of this.
Vertebrobasilar insufficiency can produce vertigo, often accompanied by unsteadiness and visual changes. Symptoms may be provoked by head position and often include headache. Importantly, however, patients with cerebellar infarction occasionally present with vertigo without other symptoms or signs of neurological impairment. Treatment involves addressing cardiovascular risk factors as well as antiplatelet therapy.
Migrainous vertigo is an increasingly recognized condition that is incompletely understood. In the acute setting, it poses a diagnostic challenge that will often necessitate exclusion of other central causes for vertigo, such as cerebrovascular disease.
Controversies
Identifying and determining disposition for syncope patients who do not fall into the high- or low-risk groups.
Role of a dedicated syncope evaluation unit.
The use of corticosteroids to treat vestibular neuritis.
Further reading
1. American College of Emergency Physicians. Clinical Policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope. Ann Emerg Med. 2007;49:431–444.
2. Colivicchi F, Ammirati F, Melina D, et al. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department. Eur Heart J. 2003;24:811–819.
3. Hing R, Harris R. Relative utility of serum troponin and the OESIL score in syncope. Emerg Med Australas. 2005;17:31–38.
4. Jhanjee R, Benditt DG. Syncope. Disease-a-Month. 2009;55:532–585.
5. Kerber A. Vertigo and dizziness in the emergency department. Emerg Med Clin N Am. 2009;27:39–50.
6. Kessler C, Tristano JM, De Lorenzo R. The emergency department approach to syncope: evidence-based guidelines and prediction rules. Emerg Med Clin N Am. 2010;28:487–500.
7. Linzer M, Yang EH, Estes M, et al. Diagnosing syncope Part 1: value of history, physical examination and electrocardiography Clinical efficacy assessment project of the American College of Physicians. Ann Int Med. 1997;126:989–996.
8. Ouyang H, Quinn J. Diagnosis and evaluation of syncope in the emergency department. Emerg Med Clin N Am. 2010;28:471–485.
9. Quinn JV, Stiell IG, McDermott DA, et al. Derivation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes. Ann Emerg Med. 2004;43:224–232.
10. Quinn JV, Stiell IG, McDermott DA, et al. Prospective validation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes. Ann Emerg Med. 2006;47:448–454.
11. Seemungal BM. A practical approach to vertigo. Pract Neurol. 2008;8:211–221.
12. Serrano LA, Hess EP, Bellolio MF, et al. Accuracy and quality of clinical decision rules for syncope in the emergency department: a systematic review and meta-analysis. Ann Emerg Med. 2010;56:362–373.
8.7 Weakness
Tim Green and Eileen M Rogan
Essentials
1 The differential diagnosis of weakness in the emergency department (ED) is very broad. Careful history taking and examination with targeted investigations will help identify most of the important causes.
2 Causes of weakness must be distinguished as neuromuscular or non-neuromuscular.
3 Most patients presenting to ED with a complaint of weakness have a non-neuromuscular cause underlying their symptoms.
4 Guillain–Barré syndrome is the most common cause of acute onset symmetrical progressive weakness in the developed world. Patients presenting with acute onset symmetrical weakness require early assessment of their airway and ventilation. Early intubation should be considered in high-risk cases. ICU admission is required for any patient with impaired ventilatory function.
5 Patients presenting with a multiple sclerosis relapse should usually be offered pulse steroid therapy in the form of methylprednisolone 1 g IV daily for 3 days (or equivalent oral dosage).
6 Supportive care is the priority in ED management in cases of weakness due to any cause.
7 If a neuromuscular cause is suspected, disposition decisions should be made in consultation with a neurologist.
8 Some patients with weakness will not be definitively diagnosed in the ED and may require referral for further investigations.
Introduction
Weakness is a subjective term that patients use to describe feelings of malaise, fatigue or frailty that they experience as the result of myriad medical and psychological conditions. The Oxford Dictionary defines ‘weak’ as ‘lacking the power to perform physically demanding tasks; having little physical strength or energy’.
For the purpose of this chapter, we will mainly consider the assessment and management of patients presenting with acute onset, generalized, symmetrical or rapidly progressive weakness, primarily in the context of neuromuscular disease. We will not discuss conditions that cause focal or unilateral weakness in any great depth, nor weakness related to non-neuromuscular causes. It should, however, be remembered that the latter group constitutes the majority of patients presenting to the emergency department (ED) complaining of weakness.
Aetiology and pathogenesis
Complaints of weakness are essentially either due to a neuromuscular problem or not. The primary goal in ED is to determine if there is actual quantitative loss of muscle strength indicative of a neuromuscular cause or whether weakness is resulting from a non-neuromuscular cause. The latter cases are often the result of multiple system disorders, for example endocrine, cardiac and metabolic factors.
Neuromuscular weakness may reflect deficits anywhere along the neural pathway from cerebral cortex to the myocyte. This pathway includes the pyramidal system as upper motor neurons (UMN) synapse with lower motor neurons (LMN) of the anterior spinal cord. LMN axons then descend through the anterior spinal cord to exit and synapse with myocytes. At the neuromuscular junction, LMNs release the presynaptic neurotransmitter acetylcholine (Ach) into the synaptic cleft and post-synaptic Ach receptors then trigger depolarization of the motor end plate and contraction of the muscle cell. Pathology at any level of this neural pathway will result in weakness. An intact myelin nerve sheath, functioning calcium and sodium channels and the presence of acetylcholinesterase to limit the response are all necessary for normal neuromuscular function.
Specific signs, such as altered deep tendon reflexes (DTRs) and tone, muscle atrophy, fasciculations and distribution of weakness, aid in localizing the site of the neuromuscular pathology (Table 8.7.1).
Table 8.7.1
Clinical signs that distinguish origin of neuromuscular weakness
UMN: upper motor neurons; LMN: lower motor neurons; NMJ: neuro muscular junction
Non-neuromuscular causes of weakness are myriad and generally reflect a combination of age, general physical and mental health factors and specific systematic disorders that co-exist to result in a general feeling of weakness or malaise (Table 8.7.2).
Table 8.7.2
Non-neuromuscular conditions associated with weakness
|
Condition |
Manifestations |
|
Anaemia |
Breathlessness, fatigue usually worse if acute onset anaemia |
|
Cardiac failure |
Fatigue and weakness are common symptoms of heart failure in elderly patients, especially weakness in females over 50 years |
|
Malignancy |
Paraneoplastic syndromes, e.g. generalized wasting |
|
Psychological disorders |
Depression/anxiety; psychosis; medication side effects; malingering |
|
Malnutrition |
Institutionalized patients; impoverished elderly; anorexia nervosa |
|
Chronic fatigue syndrome |
Possibly post-viral syndrome |
|
Rheumatological disorders |
Rheumatoid arthritis, systemic lupus erythematosus, fibromyalgia |
|
Medications |
Many medications have been associated with weakness but the commonly encountered ones include: glucocorticoids, statins, antiretrovirals, alcohol, colchicine and polypharmacy especially in the elderly |
|
Acute electrolyte derangement, e.g. hypo-, hyperkalaemia, hypo-calcaemia |
Acute onset weakness,±tetany with hypocalcaemia |
|
Sepsis |
Acidosis, deranged metabolic state |
|
Dehydration |
Lethargy/fatigue |
|
Hypothyroidism |
Lethargy, cold intolerance, weight gain, weakness |
|
Chronic disease |
Respiratory, renal, hepatic failure |
Pathology
Diverse pathological processes may underlie neuromuscular weakness. Of these, genetic, autoimmune and toxic causes predominate in the ED (Table 8.7.3). Patients with congenital genetic syndromes, such as muscular dystrophies or mitochondrial disorders, are rarely seen in the ED unless they are suffering from acute respiratory decompensation in the context of an acute reversible precipitant, such as pneumonia. Management of these cases will be guided by consideration of the clinical context, the stage of disease and disability and any advance care directives from the patient or their advocates.
Table 8.7.3
Key features of conditions associated with the symptom of weakness
In industrialized countries such as Australia, Guillain–Barré syndrome (GBS) is the most common cause of acute onset neuromuscular weakness. GBS variants, multiple sclerosis (MS) and myasthenia gravis (MG) are other autoimmune disorders that precipitate ED presentations, either as de novo diagnoses or in the context of acute exacerbations. Toxic triggers, such as organophosphates, tetanus, botulism and envenomations, are relatively rare but can be fatal if not recognized and treated aggressively.
Other pathologies, such as paraneoplastic syndromes (Eaton–Lambert syndrome) and electrolyte disturbances (e.g. hypokalaemic periodic paralysis), should be considered if the clinical context is suggestive. Poliomyelitis is an example of an infectious disease that was previously a major cause of acute onset weakness. It has been eradicated in the Western world and is well on the way to eradication in the developing world. Post-polio syndrome is a rare late complication seen in ED.
Differential diagnosis
The differential diagnosis of weakness in the ED is very broad and the definitive diagnosis may not be able to be elucidated during the course of one ED visit. Recognition of neuromuscular disorders that have the potential to deteriorate rapidly and require intensive supportive care with assisted ventilation is the most crucial element of ED diagnosis. In particular, GBS, MS exacerbations, myasthenic crises and intoxications, such as botulism, must be recognized early.
Clinical features
The diagnosis of neuromuscular disease is dependent upon history, examination and specific investigation findings. A starting point for diagnosis should include a thorough history, noting in particular:
known underlying neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), muscular dystrophy, MS or MG
pre-existing medical conditions, such as malignancy suggesting a paraneoplastic syndrome, monoclonal gammopathy associated with chronic inflammatory polymyopathy (CIDP) or HIV infection/post-transplant immunosuppressive states associated with CIDP, polyradiculopathy or HIV myopathy
recent infections (diarrhoeal, viral) or major surgery – associated with GBS
recent exposures/ingestions suggestive of intoxications, for example botulism, organophosphate, ciguatera toxin.
Clinical findings generally reflect the site of the lesion within the motor unit (see Table 8.7.1).
Clinical investigations
Given the broad differential diagnosis possible for weakness, a broad screen of laboratory parameters including full blood count (for anaemia or inflammation), electrolytes and renal function, liver function, thyroid function plus muscle creatine kinase, inflammatory markers (erythrocyte sedimentation rate [ESR] and C reactive protein [CRP]) as indicated, should be measured. ECG should be performed urgently if an electrolyte imbalance is possible. A rheumatoid screen may be suggested by clinical signs. Lumbar puncture may be indicated and can be performed to corroborate the diagnosis of GBS or MS if there are no contraindications. Specific investigations, such as brainstem evoked potentials and magnetic resonance imaging (MRI) scanning for MS should be arranged by specialist neurology services. Chest X-ray or computed tomography (CT) scan may be indicated to exclude thymoma in association with MG.
Treatment and prognosis
The mainstay of treatment for weakness caused by neuromuscular disorders is supportive care with a particular focus on ventilatory support commenced early rather than later, as emergency intubations are associated with higher complication rates. General supportive measures will also include maintenance of homeostasis with respect to normothermia, euglycaemia, normotension and control of any other autonomic dysregulation, such as paralytic ileus and urinary retention.
Prophylaxis against peptic ulcers and deep vein thrombosis and pressure area care are all crucially important in the mechanically ventilated and sedated patient. This will require ICU admission but treatment is usually commenced in the ED. Early neurological consultation and ICU review is crucial, especially for conditions in which there are effective interventions, such as plasmapheresis or intravenous immunoglobulin (IVIG) administration for GBS. For acute envenomations or intoxications, supportive care is still the priority in combination with antivenoms or antidotes, when indicated.
For non-neuromuscular causes of weakness, the treatment priority is to address the underlying disease state. This will variously include electrolyte reconstitution, rehydration, correction of thyroid function, treatment of systemic diseases and infections, optimization of organ function or psychological assessment as indicated by clinical assessment and investigations. Appropriate referral should follow. In cases where no apparent cause can be found for a complaint of weakness, an expectant approach is warranted.
The prognosis for neuromuscular disease depends on the specific condition.
Criteria for diagnosis
Table 8.7.3 summarizes the key pathophysiology, assessment findings to elucidate and management strategies for the conditions likely to present to the ED with weakness as a predominant feature.
Specific conditions
Guillain–Barré syndrome
Guillain–Barré syndrome is an acute, acquired, inflammatory demyelinating polyradiculoneuropathy (AIDP) caused by autoimmune attack on peripheral nerves/nerve roots. It is the most common cause of acute progressive generalized weakness in the ED. GBS variants exist, such as the Miller–Fisher syndrome with particular ocular muscle involvement, but these are much less common. GBS has an annual incidence in the developed world of about 1–2 cases per 100 000 and mortality of 3–10%. It is more common as people get older.
Pathophysiology
The pathophysiology involves an aberrant autoimmune response associated in about two-thirds of cases with an antecedent respiratory or gastrointestinal tract infection 3 weeks or less before the onset of signs. Campylobacter jejuni is the most commonly associated pathogen (up to 40% of cases) and a positive C. jejuni IgM titre is associated with a worse prognosis. Cytomegalovirus is the second most common infection associated with GBS. Others include Epstein–Barr virus, Mycoplasma pneumoniae, HIV and Haemophilus influenzae.
Clinical features
The hallmark of GBS is progressive ascending weakness with loss of DTRs with maximal weakness present within 2–4 weeks after onset. Proximal and distal limb muscles, truncal and respiratory muscles are affected. Cranial nerve involvement is common with facial nerve palsy in up to 70% of cases. Ocular muscle involvement is less common. Sensory symptoms are common but variable with paraesthesias or even severe pain in some patients. Autonomic dysregulation occurs in about two-thirds of patients and can be fatal due to severe fluctuations in blood pressure and cardiac arrhythmias.
The diagnosis of GBS is based on suggestive history (e.g. recent diarrhoeal infection or major surgery), clinical features of an ascending weakness with loss of DTRs and exclusion of other pathologies.
Clinical investigations
Lumbar puncture should be performed and classic CSF findings are of high CSF protein and normal glucose and cell count. Mild CSF pleocytosis is common; however, the presence of CSF leucocytosis should prompt careful consideration of alternative diagnoses, such as lymphoma or HIV.
Complications
Respiratory failure may occur in up to 30% of cases and is the most life-threatening short-term complication of GBS. This is attributed to the high incidence of phrenic nerve involvement.
Treatment
Attention to ventilation is a priority of treatment. Assessment of FVC every 2–4 hours during the acute phase is recommended and FVC of 10–12 mL/kg (<30% of predicted) is generally considered to be an indication for intubation and assisted ventilation. Other suggested criteria for elective intubation and ventilation include significant respiratory distress, fatigue, sweating, tachycardia, active aspiration and PaCO2>50 mmHg. That said, clinical judgement should guide the decision to intubate as respiratory distress and fatigue often indicate significant respiratory embarrassment prior to PaCO2 or FVC becoming deranged, particularly if the condition is rapidly deteriorating or if the patient has significant co-morbidity, for example, active cardiac ischaemia or heart failure. Swallowing difficulty and inability to lift the head or elbow off the bed are features predicting the need for intubation. Elective intubation is associated with less adverse events than a late emergency intubation so the timing of intervention needs to be carefully considered. About 25% of patients with GBS who cannot mobilize and 30–50% of patients admitted to ICU need mechanical ventilation. Of note, non-invasive ventilation (NIV) is not recommended for GBS and respiratory failure, especially if there is significant bulbar weakness.
Intravenous immunoglobulin (IVIG–usually 2 g/kg over 3–5 days) has largely replaced plasmapheresis in the treatment of GBS after large studies showed them to be equally efficacious. There is also easier access to IVIG in most hospitals.
Prognosis
Most people fully recover but a significant minority (20%) survive with persistent neurological deficits. The most common causes of death are the complications of dysautonomia and respiratory failure.
Multiple sclerosis
Multiple sclerosis (MS) is a chronic demyelinating condition. It is the commonest chronic neurological condition with an estimated prevalence of 40 000 cases in Australia. Incidence is related to latitude with Tasmania having among the highest incidence in the world (1:1000). Sixty per cent of cases occur in women. MS is frequently characterized by exacerbations and remissions. It is usually diagnosed in individuals aged 15–45 years.
Common relapse patterns include ataxia, proximal weakness (more frequently in the lower limbs), urinary symptoms and cranial nerve disorders, such as optic neuritis, diplopia and vertigo. Fatigue is a common symptom in MS and should be distinguished from a focal relapse. Heat sensitivity is a common phenomenon in MS and symptoms are often worse in summer. Exacerbations associated with febrile illness can be minimized with careful antipyretic therapy.
Undiagnosed patients may present to the ED with myriad neurological symptoms, although life-threatening presentations with respiratory compromise are exceedingly rare.
Clinical investigations and diagnosis
The diagnosis is usually made when typical clinical features are supported by the findings of neuroimaging (MRI), CSF examination and evoked potentials. Nearly all MS patients show discrete white matter lesions or homogeneous periventricular lesions on T2-weighted MRI of brain and/or spinal cord. Elevated protein and gammaglobulins (oligoclonal bands) and pleocytosis with mild lymphocytosis are the typical CSF findings. Delays in latencies on visual, somatosensory or brainstem evoked potential testing are diagnostic of demyelination in the visual pathways, posterior columns or auditory pathways, respectively.
Treatment
Relapses usually respond to brief pulse therapy with corticosteroids (methylprednisolone 1 g IV daily for 3 days or equivalent oral dosage). More severe episodes may require high dose corticosteroids and plasmapheresis therapy.
Vitamin D has now been confirmed as an important aetiological factor in MS and a vitamin D level of 150–200 nmol/L obtained by sun exposure and/or vitamin D supplementation is recommended. A range of dietary and lifestyle interventions are also associated with better outcomes in MS. Long-term disease modification therapies are increasingly available and are the remit of the neurologists. It is important to be aware of these therapies, as patients may present with side effects from these increasingly potent immune-modulating drugs.
Disposition
Neurology consultation for directing investigations and management is indicated for all patients with MS exacerbations and hospital admission is often required.
Myasthenia gravis
Myasthenia gravis (MG) is rare but the prevalence is rising in developed countries due to earlier diagnosis and good survival rates. During exacerbations, patients are very likely to attend an ED with localized or, less commonly, generalized weakness. The disease is caused by an idiopathic autoimmune attack of post-synaptic Ach receptors, leading to weakness of the muscle response to stimulus. The weakness tends to be fatiguable and is usually relieved by rest. Most patients experience facial and bulbar muscle weakness so dysphagia and dysarthria are common symptoms. More serious exacerbations are associated with respiratory compromise.
Myasthenic crisis, which occurs in 15–20% of patients (mostly within the first 2 years of diagnosis when the disease has an unpredictable course), refers to generalized weakness with respiratory failure requiring intubation and mechanical ventilation. Respiratory failure rarely presents in isolation. Myasthenic crisis can be precipitated by acute disease progression, intercurrent infections, pregnancy, surgery and by treatment with high-dose glucocorticoids, anticholinesterases and a long list of other medications that may affect neuromuscular transmission.
Diagnosis
The diagnosis is based on clinical features and demonstration of antibodies to the Ach receptor which are found in about 85% of cases. Clinical suspicion of MG can be supported by a positive bedside ice-pack test in patients with ptosis, where the eyelids are covered with an ice pack for 2 minutes with improvement in the ptosis seen immediately. The Tensilon test is now rarely performed. Electromyography (EMG) may be necessary to differentiate MG from GBS, myopathy or motor neuron disease.
Treatment and disposition
Supportive care is the main priority in ED. Neurological consultation is mandated by suspicion of MG. Treatment for MG should not be commenced until the diagnosis has been confirmed. Many patients take pyridostigmine long term and the dose may be increased in exacerbations. Paradoxically, high-dose pyridostigmine can lead to acute deterioration, so the treatment decisions should always be made in consultation with a neurologist.
Respiratory failure is the main life-threatening issue in acute myasthenic crisis; however, the condition tends to fluctuate so reliable criteria for intubation are difficult to define. Serial measurement of PEF/FVC and PaCO2 are recommended. Intubation is recommended for marginal or deteriorating patients, as elective intubation is associated with fewer complications. Early use of NIV (BiPAP) has been shown to be of benefit in myasthenic crisis in reducing the need for intubation. Plasmapheresis and IVIG (2 g/kg over 3–5 days) have also been shown to be effective in myasthenic crisis. Corticosteroids may exacerbate the condition, so should be avoided unless the patient is mechanically ventilated. In some patients, thymectomy or immunosuppressive strategies are indicated.
Prognosis
The mortality of myasthenic crisis is about 4% overall, with age>50 years and FVC<25 mL/kg predictors of poor outcome and long ICU stay. Most patients with MG have a normal lifespan.
Cord compression/cauda equina syndrome
Patients may present with weakness from acute or chronic conditions that lead to compression of the spinal cord and nerve roots, usually due to a combination of progressive age-related spinal stenosis, infections or malignancy. Progressive spinal stenosis is a common feature of ageing and can occur in isolation or be associated with acute disc herniations. Acute deterioration or sudden onset neurological deficits in the presence of other systemic illness, such as fever, should be ‘red flags’ that prompt urgent consideration and investigation for sinister pathologies. These include malignancy (e.g. lymphoma or metastatic deposits), infection (e.g. epidural abscess or discitis especially in high-risk groups, such as intravenous drug users (IVDU) or patients who have had recent epidural or spinal anaesthetics) or trauma (e.g. falls in the elderly). Any patient presenting to the ED with lower limb neurological deficits, in particular with signs of bladder or bowel dysfunction, warrants urgent imaging (MRI) to assess for spinal cord compression. Therapeutic interventions including antibiotics, surgical decompression and radiotherapy will be tailored to the individual patient following specialist consultation.
Amyotrophic lateral sclerosis (motor neuron disease)
Motor neuron disease (MND)/amyotrophic lateral sclerosis (ALS) is a rapidly progressive muscle atrophy and weakness caused by degeneration of both upper (UMN) and lower motor neurons (LMN). It causes a variable picture of spasticity, hyperreflexia and muscle weakness with an inexorable decline to respiratory failure and dependence on mechanical ventilation, usually within 2–4 years. UMN or LMN bulbar muscle weakness is invariably present and complicates the condition with aspiration and impaired cough. There is no curative therapy and treatment is therefore supportive. In the ED, ALS patients usually present with acute respiratory compromise as a result an acute precipitant, such as aspiration pneumonia or a choking episode. Management of these patients will be directed at treating the precipitant and increasing respiratory support during the period of acute exacerbation as directed by the patient and any advance care plans they might have in place. NIV should be avoided due to the risks of aspiration and increased work required by already weak respiratory muscles. Medications that reduce respiratory drive, such as opiates, should also be avoided. New diagnoses are rarely made in the ED and, if so, usually present with variable UMN and LMN signs and variable weakness. Neurological consultation is mandated by such presentations.
Eaton–Lambert syndrome
Eaton–Lambert syndrome (ELS) is a rare autoimmune paraneoplastic condition that is usually associated with small cell lung cancer. The major clinical feature is severe limb weakness as a result of autoimmune destruction of voltage-gated calcium channels in the presynaptic membrane at the neuromuscular junction which, in turn, inhibits release of presynaptic Ach vesicles. It often improves with exercise, which distinguishes it from MG. Tendon reflexes are variable but usually reduced. EMG is required to confirm the diagnosis. Management is to treat the underlying malignancy and therefore prognosis depends upon the prognosis of the malignancy. Symptomatic treatments, such as glucocorticoids, are usually ineffective. Supportive care is the goal of ED management.
Myopathies
Congenital muscular dystrophies
The X-linked disorders Duchenne muscular dystrophy and Becker muscular dystrophy are the most common forms of congenital muscular dystrophy. Boys with Duchenne muscular dystrophy are normal at birth but by age ≈5 years exhibit proximal weakness which gradually deteriorates until they are wheelchair- dependent by age 10–12 years. Thereafter, the weakness progresses inexorably and average lifespan is only ≈21 years before death due to respiratory failure. Becker muscular dystrophy has a later onset and slower progression so immobility and respiratory complications may occur in adult life and many patients have a normal life span. ED presentations in both of these conditions are almost always related to respiratory compromise due to disease progression or an acute precipitant, such as pneumonia. The management is supportive and aimed at treating any acute precipitants, as guided by disease stage, patient preference and any advance care directives.
Mitochondrial myopathies, such as those associated with MELAS syndrome, tend to present to ED similarly, with variable weakness and fluctuating conscious state on a known background of mitochondrial disorder. Ventilatory support and the attendant supportive care are the key aspects of treatment. In these cases, a brief period of mechanical ventilation can support the patient through an acute exacerbation and they may return to being relatively independent until the next acute deterioration. Management should be guided by the patient and their neurologist.
Inflammatory myopathies: polymyositis/dermatomyositis
Polymyositis and dermatomyositis are idiopathic inflammatory myopathies that mostly affect women over 30 years of age. Dermatomyositis is associated with a heliotrope rash, erythroderma and other skin changes and is more commonly associated with cancer. Patients present with proximal symmetrical weakness associated with muscle pain and tenderness. Deep tendon reflexes are intact unless weakness is severe. There are no sensory or autonomic deficits. Proximal weakness is demonstrated by asking the patient to stand from a chair while folding their arms or by asking them to lift an object above the head. In severe cases, respiratory function may be affected. Diagnosis is based on clinical findings and elevated ESR and creatine kinase (CK). Management is with immunosuppressive agents, primarily corticosteroids. Differential diagnosis includes HIV myopathy, viral myositis or myositis due to substances, such as alcohol, statins, corticosteroids and AZT. Endocrine myopathies occur rarely.
Acute periodic paralysis
Acute periodic paralyses are an interesting group of rare disorders occasionally seen in the ED. These may be associated with normal, low or elevated serum potassium. Patients are usually well between attacks but some can have residual muscle stiffness. A genetic defect has been linked to these diseases but, in some instances, hypokalaemia may cause acute weakness in healthy individuals.
Acute hypokalaemic periodic paralysis may be primary (i.e. familial) or secondary to excessive renal or gastrointestinal losses or endocrinopathy. Familial periodic paralysis usually occurs in Caucasian males, is autosomal dominant and may last as long as 36 hours. Attacks usually occur at night or in the early morning upon awakening and can be precipitated by a diet high in carbohydrates, rest following exercise or glucose and insulin given intravenously. Supportive care and replenishment of serum potassium are the main management priorities.
Thyrotoxic periodic paralysis associated with hypokalaemia is a condition more common in Asian males. Treatment of the underlying disease and electrolyte disorder are the goals of treatment.
Rhabdomyolysis
Rhabdomyolysis is a disorder with many causes that leads to muscle necrosis and the release of intracellular muscle constituents into the circulation. The characteristic triad in rhabdomyolysis is weakness, muscle pain and dark urine. Causes can be classified as due to trauma or compression, exertional and non-exertional. Non-exertional causes include drugs, toxins, viruses and electrolyte abnormalities. ED management is dependent on the cause and the emphasis is on preservation of renal function.
Intoxications
Botulism
Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. It is characterized by severe descending weakness and gastrointestinal slowing. In adults, the toxin is ingested preformed in foodstuffs whereas, in infants, the disease is usually due to ingestion of foods containing the bacterial spores, such as honey. Botulinum toxin acts at the neuromuscular junction, where it inhibits Ach release from the presynaptic membrane. Early characteristic findings include normal mentation with bulbar weakness manifesting as dysphagia and extraocular palsies with absent papillary light reflex (which distinguishes botulism from myasthenia gravis). Limb weakness is more obvious proximally and deep tendon reflexes are usually intact. Sensation is not affected. Postural hypotension tends to be a feature in adults. Management is supportive with ventilatory support in ICU if necessary. An antitoxin is available.
Tetanus
Tetanus is an acute painful paralytic illness caused by the tetanospasmin toxin of the soil-dwelling organism Clostridium tetani. It is characterized by painful severe uncontrolled skeletal muscle spasms. Respiratory muscle involvement leads to hypoxia and death. It remains endemic throughout the world and most of the 1 000 000 cases annually occur in developing countries. In the developed world, tetanus should be considered in the elderly and vulnerable groups like the homeless and poor in particular, where tetanus-prone wounds and lack of immunization are more common. Typically, tetanus is caused by a deep penetrating wound but up to 50% of patients have only a trivial, if any, wound evident. The onset is highly variable – from days to months. Generalized tetanus is the most common form and causes generalized skeletal muscle spasms, which can be greatly exacerbated by minor stimuli, such as touching or loud noise. Trismus or ‘lockjaw’ is the classic initial presenting symptom with spasm of the masseter muscle. Other early symptoms include myalgias, cramps, dysphagia and drooling. Violent muscle spasms can cause vertebral and long bone fractures. Death is due to either respiratory failure or autonomic dysfunction. The illness is progressive with an increase in severity over 3–5 days and a gradual reduction after 10 days. Diagnosis is on clinical grounds alone and supportive care with sedation and ventilation, administration of tetanus antitoxin and avoidance of complications are the priorities in treatment. Localized tetanus also occurs with spasms localized near the original wound site and rarely progresses to generalized tetanus. This variant carries a good prognosis with or without treatment.
Envenomations
Several envenomations can present to the ED with weakness as part of the clinical syndrome. These include the Ixodes holocyclus paralysis tick, puffer fish and blue-ringed octopus (tetrodotoxin) and reef fish (ciguatera toxin) (see Table 8.7.3). These envenomations are covered in detail elsewhere.
Controversies and future developments
A number of the causes of weakness discussed in this chapter including GBS, cord compression and MS are misdiagnosed in the ED or diagnosed late and are overrepresented in medicolegal claims arising from the ED. Emergency physicians must maintain a high level of critical thinking to distinguish functional, non-neuromuscular and time-critical neuromuscular emergencies.
Orthodox neurological opinion stresses the primacy of modern immune modulating therapies for management of relapsing-remitting MS. Recent studies suggest an equally important role for other therapeutic approaches including vitamin D supplementation, avoidance of animal fat, promotion of a whole food diet rich in fish and omega 3 fatty acids and meditation/stress reduction techniques.
Plasmapheresis and IVIG have both been advocated as definitive therapy for GBS. Recent studies suggest superiority of IVIG.
Ventilatory support for patients with GBS should be instituted early when indicated, while patients with end-stage muscular dystrophy, MELAS, MND/ALS or MG present difficulties for emergency physicians balancing quality of life, potential reversibility and the patient’s expressed advance care directive. Therapeutic decisions must be made with extensive consultation with the treating neurologist, patient and family. NIV may be an effective modality in patients with MG but should be avoided in cases of GBS and MNS/ALS where intubation and mechanical ventilation is preferred.
Further reading
1. Burton JM, O’Connor PW, Beyene J. Oral versus intravenous treatment for relapses in multiple sclerosis. Cochrane Database Syst Rev. 2009;3:CD006921.
2. Greenberg D, Aminoff M, Simon R. Motor disorders. In: Greenberg D, Aminoff M, Simon R, eds. Clinical neurology. 8th ed. New York: McGraw-Hill; 2012.
3. Hart IK, Sathasivam S, Sharshar T. Immunosuppressive agents for myasthenia gravis. Cochrane Database Syst Rev. 2007;4:CD 005224.
4. Holmay T, Kampma M, Smolders J. Vitamin D in multiple sclerosis: implications for assessment and treatment. Exp Rev Neurother. 2012;12:1101–1112.
5. Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2012;7:CD002063.
6. Jagannath VA, Fedorowicz Z, Asokan GV. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2012;12:CD008422.
7. Jelinek G. Overcoming multiple sclerosis: an evidence-based guide to recovery Australia: Allen and Unwin; 2010.
8. Longo D, Fauci A, Kasper D. Weakness and paralysis. In: Longo D, Fauci A, Kasper D, eds. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill; 2012.
9. Mehndiratta MM, Pandey S, Kuntzer T. Acetylcholinesterase inhibitor treatment for myasthenia gravis. Cochrane Database Syst Rev. 2011;2:CD 006986.
10. Minagar A, Rabinstein A. Neurologic emergencies. Neurol Clin. 2012;30:1–404.
11. Murray L, Daly F, Little M, Cadogan M, eds. Toxicology handbook. 2nd ed. Churchill-Livingstone/Elsevier 2010.
12. Ropper A, Samuels M. Motor paralysis. In: Ropper AH, Samuels MA, eds. Adams and Victor’s principles of neurology. 9th ed. New York: McGraw-Hill; 2009.