Ischaemic stroke

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Ischaemic stroke
The right clinical information, right where it's needed
Last updated: Oct 18, 2018
Table of Contents
Summary
3
Basics
4
Definition
4
Epidemiology
4
Aetiology
4
Pathophysiology
5
Classification
5
Prevention
7
Primary prevention
7
Secondary prevention
7
Diagnosis
9
Case history
9
Step-by-step diagnostic approach
9
Risk factors
13
History & examination factors
16
Diagnostic tests
19
Differential diagnosis
22
Treatment
24
Step-by-step treatment approach
24
Treatment details overview
28
Treatment options
30
Follow up
39
Recommendations
39
Complications
39
Prognosis
41
Guidelines
42
Diagnostic guidelines
42
Treatment guidelines
42
Online resources
45
Evidence scores
46
References
47
Images
57
Disclaimer
61
Summary
◊ A leading cause of morbidity and mortality.
◊ Approximately 85% of strokes are ischaemic, caused by vascular occlusion.
◊ A clinical emergency: timely diagnosis, triage, and intervention can improve outcome.
◊ Care of patients in dedicated stroke units improves survival and function.
◊ Intravenous recombinant tissue plasminogen activator is given within 4.5 hours of stroke onset.
◊ Endovascular interventions, such as clot retrieval devices or intra-arterial thrombolysis, can be used
in carefully selected patients within 6 hours of ischaemic stroke onset.
Ischaemic stroke
Basics
BASICS
Definition
Stroke is defined as an acute neurological deficit lasting more than 24 hours and caused by cerebrovascular
aetiology. It is further subdivided into ischaemic stroke (caused by vascular occlusion or stenosis) and
haemorrhagic stroke (caused by vascular rupture, resulting in intraparenchymal and/or subarachnoid
haemorrhage). Central venous sinus thrombosis is a rare form of stroke that occurs due to thrombosis of the
dural venous sinuses. This monograph deals with ischaemic stroke.
Transient ischaemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal
brain, spinal cord, or retinal ischaemia, without acute infarction. Patients with TIAs are at high risk for early
ischaemic stroke,[1] and their risk may be stratified by clinical scale, vessel imaging, and diffusion magnetic
resonance imaging.[2] This replaced the former definition of focal neurological impairment lasting less than
24 hours.
Epidemiology
Stroke is the third leading cause of death and a major cause of disability in the US[6] and in England and
Wales, and the third leading cause of death in Canada.[7] In Scotland in 2016/17 the incident rate for
stroke, standardised by age-sex, was 180 per 100,000.[8] There are approximately 610,000 new strokes
per year in the US.[9] Ischaemic stroke accounts for 87% of all stroke cases, haemorrhagic stroke for
10%, and subarachnoid haemorrhage for 3%.[9] Ischaemic stroke prevalence can be further sub-divided
according to pathophysiological mechanism: extracranial atherosclerosis (10%), intracranial atherosclerosis
(10%), cardioembolic (25%), lacunar infarction ([small vessel disease] 15%), indeterminate aetiology ([i.e.,
cryptogenic] 30%), or other defined causes (10%). Ischaemic stroke is more common in older people, people
with lower levels of education, and African-American or Hispanic people.[9] The overall incidence of stroke as
well as stroke mortality has been decreasing over the last few decades, presumably due to effective primary
prevention and management.
Aetiology
Ischaemic stroke is a syndrome, not a disease. It is caused by a transient or permanent critical reduction
in cerebral blood flow due to arterial occlusion or stenosis. Identification of the underlying mechanisms and
aetiologies is important so that appropriate therapy can be initiated to decrease the risk of recurrent stroke.
A classification scheme for ischaemic stroke developed for the Trial of Org 10172 in Acute Stroke Treatment
(TOAST) provides a framework for determining the stroke mechanism, with implications for identifying the
underlying aetiology:[3]
Large artery atherosclerosis affects the extracranial carotid or vertebral arteries, or less commonly the major
intracranial arteries. It is a site for thrombus formation that then embolises to distal sites and/or occludes the
vessel.
Small vessel (lacunar) stroke is caused by thrombotic occlusion of a small penetrating artery affected by
lipohyalinosis (lipid accumulation due to ageing and hypertension), resulting in a <1.5-cm infarct in the
perfusion territory of the affected small vessel.
4
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Ischaemic stroke
Basics
Cardioembolism results from thrombus formation in the heart, which then embolises to the intracranial
circulation, and is associated with cardiac disease such as atrial fibrillation. Accumulating evidence suggests
that aortic atherosclerotic plaque is another potential source of thrombus formation with embolism.
Strokes of indeterminate aetiology, despite complete work-up, are not uncommon. In the Northern Manhattan
Stroke Study, 32% of strokes had no identifiable aetiology.[10]
Pathophysiology
Regardless of the aetiology, ischaemic stroke occurs when blood supply in a cerebral vascular territory is
critically reduced due to occlusion or critical stenosis of a cerebral artery. A minority of ischaemic strokes are
caused by cerebral sinus or cortical vein thrombosis. These are frequently associated with a prothrombotic
(hypercoagulable or hyperaggregable) state, with resulting venous insufficiency and reduced blood flow.
Pathophysiologically, ischaemic stroke can be broadly classified as:
• Primary vascular pathologies (e.g., atherosclerosis, aortic arch atherosclerosis, arterial dissection,
migraine, or vasculitis) that directly reduce cerebral perfusion and/or result in artery-to-artery embolism
(i.e., stenosis or occlusion of a distal artery by an embolus originating in a proximal artery)
• Cardiac pathologies (e.g., atrial fibrillation, myocardial ischaemia/infarction, patent foramen ovale) that
lead to cerebral arterial occlusion due to embolism
• Haematological pathologies (e.g., prothrombotic hypercoagulable or hyperaggregable states) that
directly precipitate cerebrovascular thrombosis (particularly venous), or facilitate systemic venous or
intracardiac thrombus formation and cardioembolism.
Classification
Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria[3]
Classifies ischaemic stroke according to pathophysiology:
Large artery atherosclerosis
• Infarction in the perfusion territory of an extracranial or intracranial artery with >50% stenosis, and no
other likely cause of stroke.
Cardioembolism
• Infarction in the presence of at least 1 cardiac condition strongly associated with stroke, such as atrial
fibrillation.
Small vessel occlusion
• Infarction <1.5 cm in diameter in the perfusion territory of a small penetrating blood vessel.
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5
BASICS
Strokes of other determined aetiology may be caused by various diseases of the intracranial or extracranial
vessels (e.g., dissection, vasculitis, venous thrombosis) or haematological system (e.g., sickle cell anaemia,
antiphospholipid antibody syndrome, and other hypercoagulable states).
Ischaemic stroke
Basics
BASICS
Stroke of other determined aetiology
• Examples include cerebral infarction caused by vasculitis, arterial dissection, and hypercoagulable
states.
Stroke of indeterminate aetiology
• Infarction in the setting of 2 or more different potential aetiologies, no potential aetiology despite
complete diagnostic evaluation, or an incomplete evaluation.
Causative classification of stroke modified TOAST criteria[4]
This web-based validated classification algorithm sub-types ischaemic stroke according to pathophysiological
mechanism. Categories are:
• Large artery atherosclerosis
• Cardio-aortic embolism
• Small artery occlusion
• Other causes
• Indeterminate causes.
Indeterminate causes are divided into:
• Unknown - embolic stroke of undetermined source
• Unknown - multiple causes
• Unknown - incomplete evaluation.
Each sub-type except for the indeterminate group is sub-divided based on the weight of evidence as:
• Evident
• Probable
• Possible.
Oxford Community Stroke Project classification system[5]
Sub-types ischaemic stroke according to vascular territory of infarction:
•
•
•
•
6
Total anterior circulation infarction
Partial anterior circulation syndrome
Lacunar infarction
Posterior circulation infarction.
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BMJ Best Practice topics are regularly updated and the most recent version
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subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Ischaemic stroke
Prevention
Primary prevention
Established measures for primary prevention of stroke include physical activity; avoidance of obesity; good
nutrition; treatment of hypertension,[41] [42] hypercholesterolaemia, and diabetes; and abstinence from
smoking, illegal drug use, or heavy drinking.[43] Further preventative measures may be appropriate in
particular patient groups.
Unstable carotid atherosclerotic plaque leading to stroke is a major cause of morbidity and mortality.
Based on a Cochrane review, adjusted-dose warfarin and related oral anticoagulants reduce stroke, disabling
stroke, and other major vascular events for those with non-valvular atrial fibrillation by about one third when
compared with antiplatelet therapy.[44] Nonetheless, the benefits of anticoagulation therapy should be
weighed against the risk of haemorrhage, particularly intracranial haemorrhage, for each patient.
In patients with non-valvular atrial fibrillation, dabigatran, rivaroxaban, apixaban, and edoxaban are as
effective as warfarin in preventing stroke and carry a smaller risk of intracranial bleeding. The combination of
triflusal plus acenocoumarol is likely to be more effective than acenocoumarol alone in reducing stroke risk;
however, these drugs are not widely used and availability may vary.[45]
cardiovascular disease. Evolocumab works by inhibiting proprotein convertase subtilisin/kexin type 9 from
binding to low-density lipoprotein (LDL) receptors, increasing the number of LDL receptors available to clear
LDL from the blood, thereby lowering LDL-cholesterol levels.
Because transient ischaemic attack (TIA) is a form of stroke, prevention of further stroke in a patient with TIA
places it under the category of secondary stroke prevention.
Secondary prevention
Recommendations for the secondary prevention of ischaemic stroke have been published.[61] Established
trial-confirmed therapies for secondary ischaemic stroke prevention include:
• Anticoagulation with warfarin for atrial fibrillation.[115] Range INR should be 2.0 to 3.0 for patients
treated with a vitamin-K antagonist.[116] The HAS-BLED score may be used to assess the bleeding
risk of the patient; if high, the patient should be followed up more closely.[117] The SAME-TTR score
may be used to decide whether the patient should be treated with a non-vitamin-K oral anticoagulant
or a vitamin-K antagonist.[118]
• Antiplatelet drug therapy for non-atrial fibrillation patients.[119] [120] Based on a systematic review of
studies addressing the role of clopidogrel and modified-release dipyridamole (MRD) for the prevention
of occlusive vascular events, the evidence suggests that the most cost-effective treatment for patients
with ischaemic stroke/transient ischaemic attack (TIA) is clopidogrel followed by MRD plus aspirin,
followed by aspirin; for patients with myocardial infarction, aspirin followed by clopidogrel; and for
patients with established peripheral arterial disease or multi-vascular disease, clopidogrel followed
by aspirin.[121] Cilostazol is a new emerging potential and feasible option in acute ischaemic stroke,
and comparable to aspirin in its efficacy and safety.[122] A cohort study has found that older people
receiving daily aspirin-based antiplatelet treatment without routine proton-pump inhibitor (PPI) use
are at higher and more sustained risk of major bleeding than younger patients. In this study, half of
the major bleedings in patients aged 75 or older were upper gastrointestinal. The estimated numbers
needed to treat for routine PPI use to prevent major upper gastrointestinal bleed were low and the
authors concluded that co-prescription should be encouraged.[123]
• Carotid endarterectomy for carotid artery stenosis.[19] [20] In patients with a recent symptomatic
carotid stenosis (i.e., TIA or non-disabling stroke), endarterectomy is of some benefit for 50% to 69%
of symptomatic stenosis and highly beneficial for 70% to 99% of stenosis without near-occlusion. No
evidence of benefit was found in patients with near-occlusion.[124] Based on a large meta-analysis,
carotid artery stenting is associated with an elevated risk of both peri-procedural and intermediate- to
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7
PREVENTION
The human monoclonal antibody evolocumab has been approved by the Food and Drug Administration in
the US for the prevention of stroke, heart attack, and coronary revascularisations in adults with established
Ischaemic stroke
•
•
•
long-term harmful outcomes, but with a reduction in peri-procedural myocardial infarction and cranial
nerve injury, compared with carotid artery endarterectomy for people with carotid artery disease.
Strategies are urgently needed to identify patients who are best served by carotid artery stenting
compared with carotid endarterectomy.[125]
Statin therapy with intensive lipid-lowering effects is recommended for patients with ischaemic stroke
or TIA, to lower the risk of stroke and cardiovascular events.[61] Ezetimibe may be added to decrease
LDL-cholesterol levels further.[126] Patients who are at a very high risk for stroke recurrence and have
high LDL-cholesterol levels despite intensive lipid-lowering treatment may benefit from a proprotein
convertase subtilisin/kexin type 9 inhibitor.
Additional secondary prevention measures may be necessary depending on stroke risk factors and
associated diseases discovered during investigations for the cause of stroke.[61]
In stroke patients or those with TIA and obesity, the treating physician should consider sleep studies
because sleep apnoea is common among this subgroup of patients and treatment of apnoea with
continuous positive airway pressure may improve outcomes.[61]
In patients with embolic stroke of undetermined source and a patent foramen ovale (PFO) who have a
high ROPE score, closure of the PFO may be of benefit for secondary stroke prevention.[126]
PREVENTION
•
Prevention
8
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Ischaemic stroke
Diagnosis
Case history
Case history #1
A 70-year-old right-handed man is discovered by a family member to have difficulty speaking and
comprehending spoken language, and an inability to raise his right arm. He was last known to be fully
functional 1 hour ago when the family member spoke to him by phone. There is a history of treated
hypertension and diabetes.
Other presentations
The presenting symptoms of stroke vary by cerebral location. Most common symptoms are partial or
total loss of strength in upper and/or lower extremities, expressive and/or receptive language dysfunction,
sensory loss in upper and/or lower extremities, visual field loss, slurred speech, or difficulty with fine
motor co-ordination and gait. In most cases the symptoms appear rapidly, over seconds or minutes,
and may be preceded by one or more transient ischaemic attacks. There are no symptoms or signs
that reliably distinguish between ischaemic and haemorrhagic stroke. The acute onset of neurological
symptoms referable to the brain territory of a cerebral artery strongly suggests ischaemic stroke, but
mimicking conditions such as intracerebral haemorrhage, focal seizure, and complicated migraine need to
be considered and excluded.
Step-by-step diagnostic approach
The goals of the initial evaluation are to identify the stroke syndrome, ensure medical stability, perform an
abbreviated neurological examination (e.g., National Institutes of Health [NIH] Stroke Scale),
[VIDEO: NIH Stroke Score ]
DIAGNOSIS
and rapidly transport the patient to the computed tomography (CT) or magnetic resonance imaging (MRI)
scanner to begin scanning as soon as possible.[46] Because of time constraints, certain portions of
the history and physical examination may be deferred until after scanning and the decision to perform
thrombolysis. This is because the sensitivity and specificity to correctly diagnose and localise ischaemic
stroke from the neurological history and examination are fairly low. Additionally, many other neurological
conditions can mimic stroke. The proper diagnosis of stroke requires craniocervical CT or MRI.
In many cases, consultation with a stroke physician is helpful. This is particularly true when thrombolysis or
other acute reperfusion therapies are contemplated; guidelines recommend that thrombolysis be given by
stroke physicians following institutional written care protocols.[46]
Time of onset
The most important information in the history, apart from the presence of neurological symptoms, is
the time of onset. Time from stroke onset is the main factor that determines eligibility for acute stroke
treatments. The time of onset is not always easy to determine, particularly if the onset was not witnessed
and the patient is unable to communicate; symptoms are mild and not immediately noticeable; or there
is a stuttering or fluctuating course. In the frequent situation where the onset was unwitnessed, the
appropriate operational definition of symptom onset is the time when patient was last known to be
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9
Ischaemic stroke
Diagnosis
unaffected. This also implies that if signs and symptoms completely resolve during a fluctuating course,
the clock for determining eligibility for recanalisation may be reset.
Prior medical information relevant to the acute management of stroke includes:
•
•
•
•
•
•
•
•
•
•
•
Recent stroke
Seizure or epilepsy
Myocardial infarction
Atrial fibrillation
Recent surgery
Recent trauma
Bleeding
History of haemorrhagic stroke
Comorbidities (specifically hypertension and diabetes)
Current or past illicit drug use
Medicines (specifically anticoagulants, insulin, and antihypertensives).
Other risk factors include older age, male gender, African-American or Hispanic ancestry, smoking, other
comorbid cardiac conditions, carotid artery stenosis, and sickle cell disease.
Physicians as well as the emergency medical team attending to the patient in the field should establish
contact with witnesses or next of kin (or person with a legal right to make healthcare decisions on behalf
of the patient, such as a healthcare proxy). This is necessary not only to obtain an accurate and relevant
history but also to seek consent for invasive tests or treatments if needed.
Presenting symptoms
The presenting symptoms of stroke are highly variable depending on the mechanism and location of
stroke.
DIAGNOSIS
The most common anterior circulation stroke symptoms are:
•
•
•
•
Limb and/or facial weakness
Paraesthesias or numbness
Speech difficulty
Headache.
Posterior circulation strokes often present with:
•
•
•
•
•
Visual loss or double vision
Confusion
Dizziness
Vertigo
Nausea.
Arterial dissections may present with:
• Neck or facial pain.
Lacunar strokes often present with:
• Limb and/or facial weakness (typically affects face, leg, and arm equally)
10
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Ischaemic stroke
Diagnosis
• Speech difficulty
• Ataxia
• Paraesthesias or numbness (typically affects face, leg, and arm equally).
In most cases, the symptoms of ischaemic stroke appear rapidly, over seconds or minutes. One or more
transient ischaemic attacks (TIAs), which may be stereotypical, sometimes precede the stroke as warning
signs or symptoms. Their prompt identification with proper intervention is essential in stroke prevention.
Because stroke can be the result of a general medical illness, such as a hypercoagulable state perhaps
associated with a malignancy, or cardiac ischaemia or arrhythmia, a thorough history is often very helpful
to tailor specific management.
The ABCD2 score is a risk assessment tool that can help predict short-term stroke risk following TIA.[47]
[VIDEO: ABCD2 Score to Predict Stroke Risk after TIA ]
The score is optimised to predict the risk of stroke within 2 days after a TIA, but can also predict stroke
risk within 90 days.
Physical examination and neurological assessment
Initial assessment
• Should aim to identify airway, breathing, and circulatory insufficiencies requiring urgent treatment.
General systemic examination should seek evidence of risk factors, such as cardiac arrhythmias
or valvular pathology. Arrhythmias, murmurs, and pulmonary oedema are associated with cardiac
comorbidities, which predispose patients to stroke disease.
Neurological assessment
• As with the symptomatology, presenting signs of stroke can be highly variable depending on its
mechanism and location.
Anterior circulation strokes are commonly associated with:
Posterior circulation strokes are more commonly associated with:
•
•
•
•
•
•
•
Specific cranial nerve deficits: for example, unilateral tongue weakness, diplopia
Horner's syndrome (hemilateral triad of miosis, ptosis, and facial anhidrosis)
Visual field loss
Dysarthria
Nausea and/or vomiting
Difficulty with fine motor co-ordination and gait
Possible altered level of consciousness and coma.
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11
DIAGNOSIS
• Partial or total loss of strength in face and upper and/or lower extremities (usually unilateral)
• Expressive and/or receptive language dysfunction (aphasia)
• Sensory loss in face and upper and/or lower extremities (associated with sensory neglect if nondominant hemisphere stroke)
• Gaze paresis (often horizontal and unidirectional). Wrong-way eye deviation (i.e., gaze deviation
away from the side of the brain lesion, towards the hemiparetic side) should prompt consideration
of seizure but can also occur with strokes affecting the pons or thalamus. Horner's syndrome
suggests ipsilateral carotid dissection.
Ischaemic stroke
Diagnosis
Lacunar strokes are associated with:
•
•
•
•
•
Pure motor hemiparesis
Pure sensory hemiparesis
Ataxia
Mixed motor and sensory signs
Dysarthria.
To ensure timely but adequate neurological evaluation in acute stroke, the NIH Stroke Scale is a useful
tool for measurement of stroke-related deficits.
[VIDEO: NIH Stroke Score ]
Initial testing
After initial life support including management of airway, breathing, and circulation, the next immediate
goal is to rapidly obtain a brain image, typically a non-contrast head CT, in order to exclude a brain
haemorrhage. The ideal time from emergency department arrival to start of CT is 25 minutes.[46]
Imaging of the brain and its feeding vessels plays a crucial role in the diagnosis and better treatment of
patients with TIA or ischaemic strokes. All patients with TIA or possible ischaemic stroke should initially
undergo a CT scan of the brain to rule out intracranial haemorrhage. This test is relatively fast and
inexpensive. MRI of the brain, particularly with diffusion-weighted and gradient-echo sequences, provides
more accurate information about the stroke lesion, clearly highlights the area of ischaemic infarct, and
may provide further clues about the cause(s). However, in many medical centres around the world, MRI
is not available. Therefore, it is recommended that all patients with ischaemic stroke undergo a CT scan
of the brain without contrast, and then MRI of the brain if available.[48] Both CT and MRI data should be
reviewed and interpreted by a physician with expertise in stroke imaging.
[Fig-1]
DIAGNOSIS
[Fig-2]
[Fig-3]
While CT/MRI transport is being organised there should be simultaneous placement of an intravenous
catheter with blood sampling for:
•
•
•
•
•
•
Serum glucose
FBC
Electrolytes
Urea and creatinine
Partial thromboplastin and prothrombin times (with international normalised ratio)
Cardiac enzymes
An ECG should be performed to exclude cardiac arrhythmia or ischaemia, which are relatively common
in ischaemic stroke. Present diagnostic protocols suggest a minimum of 24 hours of ECG monitoring
after an ischaemic stroke to exclude atrial fibrillation. However, it has been found that ECG monitoring
along with insertable cardiac monitor was superior to conventional ECG monitoring in diagnosing atrial
fibrillation in cases of cryptogenic stroke.[49] In addition, one significant issue is that in patients with
cryptogenic stroke or TIA who are 55 years old or older, non-invasive ambulatory ECG with a target
12
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Ischaemic stroke
Diagnosis
of 30 days should be utilised because this enables clinicians to diagnose and treat paroxysmal atrial
fibrillation.[50]
It is important to note that administration of recombinant tissue plasminogen activator (r-tPA) should not
be delayed by these additional tests unless a specific contraindication is suspected and must be ruled
out: for example, the presence of hypoglycaemia has been associated with autonomic and neurological
symptoms, including stroke mimics and seizures, and hyperglycaemia has been associated with
intracerebral bleeding and worse clinical outcomes in patients treated with r-tPA; both hypoglycaemia and
hyperglycaemia can be excluded by bedside glucose test.[51] Blood glucose should be normalised before
initiating r-tPA treatment.[51] The recommended target time for provision of thrombolysis, if indicated, is
as soon as possible, and should be no longer than 60 minutes from emergency department arrival.[46]
Subsequent testing
Includes:
• CT angiography preferably (or MR angiography). Should be performed in all patients with
acute ischaemic stroke with suspicion of a large vessel occlusion who would be candidates for
endovascular thrombectomy.[51]
• Serum toxicology screen. Performed in selected patients if there is a suspicion of ingestion of toxic
substances. Signs and symptoms may mimic stroke.
• In the presence of cardiopulmonary signs or symptoms, a CXR can detect other relevant conditions
such as cardiomegaly, aortic dissection, or pneumonia.
Optional vascular imaging
Ultrasound studies of intracranial vessels (transcranial Doppler) or cervical carotids may be helpful to
complement the MR or CT angiographic data, and can continuously monitor changes in flow velocity.
If routine imaging studies fail to show arterial occlusion, and if the infarct imaging and clinical presentation
show characteristics of venous stroke (e.g., ischaemic tissue not conforming to a vascular territory,
severe haemorrhagic transformation and/or oedema, intractable seizures at presentation, signs of
increased intracranial pressure), then patency of cerebral venous sinuses can be assessed by CT or MR
venography.
Emerging tests
CT- or MRI-perfusion-weighted imaging identifies cerebral regions with reduced blood flow that may be
at risk for subsequent infarction. This has been proposed as a means of selecting patients, presenting
beyond 4.5 hours, who have hypoperfused but still viable tissue. These imaging methods are promising
but have not yet been fully validated for patient selection for reperfusion therapies.[52]
[Fig-4]
Risk factors
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13
DIAGNOSIS
In ischaemic stroke, conventional angiography is reserved for patients in whom endovascular intervention
is an option, or if more information is needed to better understand the haemodynamic status of ischaemic
brain (e.g., to define collateral blood supply) for further management (e.g., revascularisation).
Ischaemic stroke
Diagnosis
Strong
older age
• Even after controlling for other age-related conditions such as hypertension, this remains a strong nonmodifiable risk factor.[9]
family history of stroke
• Stroke-causing genetic disorders with mendelian inheritance are rare. However, twin studies show that
a significant portion of stroke risk is heritable, and epidemiological studies show that family history of
stroke is a risk factor.[11]
• Numerous candidate genes have been proposed, but none have yet been consistently replicated as a
strong risk factor for stroke.[12]
history of ischaemic stroke
• History of previous ischaemic stroke indicates that the patient may sustain more ischaemic strokes in
the future (particularly if risk factors, e.g., hypertension, are not corrected).
hypertension
• Strongly associated with increased incidence of ischaemic stroke.[13]
smoking
• Strongly associated with increased incidence of ischaemic stroke.[14]
diabetes mellitus
• Strongly associated with increased incidence of ischaemic stroke.[15]
atrial fibrillation
DIAGNOSIS
• Strongly implicated in the risk of cardioembolic stroke but not other ischaemic stroke sub-types.[16]
comorbid cardiac conditions
• Several other cardiac conditions have been reported as potential causes of cardioembolism, with
varying degrees of evidence. These conditions include myocardial infarction with regional wall
motion abnormalities or decreased left ventricular ejection fraction, valvular disease, patent foramen
ovale with or without atrial septal aneurysm, mitral valve prolapse, prosthetic heart valve, and
cardiomyopathy.[17]
carotid artery stenosis
• Modestly associated with risk of first ever ipsilateral ischaemic stroke and strongly associated with
stroke recurrence after ipsilateral ischaemic stroke.[18] [19]
• Degree of stenosis is related to the risk of recurrent stroke.[20]
sickle cell disease
• Associated with vascular stenosis, brain ischaemia, and Moyamoya disease (vascular occlusion
affecting circle of Willis). In children, prophylactic transfusion based on transcranial Doppler ultrasound
criteria has been shown to lower subsequent stroke risk.[21]
14
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Ischaemic stroke
Diagnosis
dyslipidaemia
• Large prospective studies have shown that increased serum total cholesterol is modestly associated
with an increased risk of ischaemic stroke.[22]
• There are few studies on the association of low-density lipoprotein cholesterol with stroke, and the
results are conflicting.[17] A meta-analysis showed that increased high-density lipoprotein is protective
against ischaemic stroke.[23]
people with lower levels of education
• Stroke symptoms are more likely among those with lower income and lower educational attainment.[9]
Weak
African-American or Hispanic ancestry
• Have been associated with increased incidence of ischaemic stroke.[9] [24] Some, but not all, of
this increased risk is accounted for by higher prevalence of known vascular risk factors such as
hypertension and diabetes.
poor diet and nutrition
• Epidemiological studies show a relationship between decreased stroke risk and increased
consumption of fruits and vegetables,[25] decreased consumption of sodium,[26] and increased
consumption of potassium.[27]
• The effects of decreased sodium and increased potassium intake may be mediated by a lower risk of
hypertension.
physical inactivity
• Decreased physical activity has been associated with increased risk of ischaemic stroke.[28]
obesity
DIAGNOSIS
• Overweight and obese people have a modestly increased risk of ischaemic stroke.[29] [30]
alcohol abuse
• Heavy alcohol use is associated with an increased risk of ischaemic stroke.[31]
• Light to moderate alcohol consumption may be protective against ischaemic stroke.[31]
oestrogen-containing therapy
• A small increased risk of ischaemic stroke may be present in users of oral contraceptive pills; however,
studies are conflicting.[32]
• Clinical trials of oestrogen or oestrogen plus progestogen in post-menopausal women have shown an
increased incidence of ischaemic stroke.[33] [34]
illicit drug use
• Several drugs may influence stroke risk. Cocaine and other drugs may cause changes in blood
pressure or vasculitic-type changes in the intracranial circulation.
• Unsafe intravenous injections may lead to infective endocarditis with subsequent cardioembolism, or
paradoxical embolism of injected foreign material.
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15
Ischaemic stroke
Diagnosis
migraine
• Case-control studies show an elevated risk of stroke associated with migraine, particularly in younger
women and in those with migraine with aura.[35]
hyperhomocysteinaemia
• Prospective and case-control studies show that higher serum homocysteine levels are associated with
a higher risk of ischaemic stroke. However, a randomised trial of homocysteine lowering to prevent
stroke showed no benefit of therapy.[36] Subsequent studies with stroke as a secondary endpoint have
shown varying results.[37] [38] Therefore, although homocysteine is clearly a marker of ischaemic
stroke risk, it remains unclear whether homocysteine itself causes stroke.
elevated lipoprotein(a)
• Most studies of lipoprotein(a) and ischaemic stroke show increased risk with higher lipoprotein(a)
levels. Lipoprotein(a) levels can be lowered with niacin, but it is not known whether lipoprotein(a)
reduction reduces the risk of ischaemic stroke.
hypercoagulable states
• Elevated anti-cardiolipin or anti-beta2-glycoprotein-1 antibody levels have been associated with stroke.
• Hereditary conditions associated with venous thromboembolism (e.g., antithrombin III deficiency,
protein C deficiency, protein S deficiency, factor V Leiden mutation, or prothrombin gene mutations)
have not been found to be risk factors for ischaemic stroke[17] but are related to the risk of cerebral
venous sinus thrombosis.
• The possibility that hypercoagulable states may be more strongly associated with certain stroke subgroups, including stroke in young people, is plausible but has not been evaluated in large studies.
elevated C-reactive protein
DIAGNOSIS
• Associated with an increased risk of stroke after controlling for other risk factors.[39] Whether it directly
causes stroke or is merely a marker of risk is uncertain.
aortic arch plaques
• Aortic arch plaques may be a risk factor for recurrent stroke and death. In cases of cryptogenic
strokes, further diagnostic tests are warranted to search for large aortic plaques.[40]
History & examination factors
Key diagnostic factors
vision loss or visual field deficit (common)
• Monocular vision loss may occur and is often transient. This is a common early warning signal
for cervical carotid stenosis. It is not necessarily a sign of cerebral stroke; however, it should be
recognised and investigated with the same urgency.
• Vision loss may occur in patients with posterior circulation ischaemia.
• When visual field loss is unilateral, this sign may reflect either carotid or vertebrobasilar ischaemia,
whereas bilateral visual field loss is usually due to vertebrobasilar ischaemia.
weakness (common)
• Complete or partial loss of muscle strength in face, arm, and/or leg is a typical presentation of stroke.
16
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Ischaemic stroke
Diagnosis
• Weakness of all 3 suggests deep hemispheric involvement, although this may not differentiate stroke
mechanism.
• As with most stroke signs and symptoms, bilateral involvement is uncommon and may reflect
alternative aetiologies.
• Hemiparesis is associated with lacunar strokes.
aphasia (common)
• Impairment in any language function, either expressive or receptive, is a sign of dominant hemispheric
ischaemia.
impaired co-ordination (ataxia) (common)
• In the absence of muscle weakness, ataxia points to ischaemia involving the cerebellum or its
connections with the rest of the brain.
• Posterior circulation strokes are more commonly associated with difficulty with fine motor co-ordination
and gait.
Other diagnostic factors
history of transient ischaemic at tack (TIA) (common)
• More than half the patients presenting with stroke related to a cervical carotid artery atherosclerosis
have a history of TIA. Conversely, patients with a history of TIA are at a significant risk of subsequent
stroke. Most of these strokes occur within days of the TIA; a pooled analysis showed that 5% of TIA
patients have a stroke within 2 days.[53]
sudden onset of symptoms (common)
• Stroke symptoms often start suddenly over seconds to minutes and may worsen in a step-wise
fashion, fluctuate, or stutter.
• Slowly progressive symptoms often reflect other aetiologies, such as intracerebral haemorrhage.
• It is important to differentiate multiple, step-wise worsening from a gradual decline.
• Stroke often presents with negative symptoms such as visual loss, numbness, or weakness.
• Positive symptoms such as marching paraesthesias, visual hallucinations, and abnormal motor
manifestations are more likely to be related to complicated migraine or seizure. There are occasional
exceptions to the rule.
altered sensation (common)
• Patients often describe sensory loss and paraesthesias as numbness.
headache (common)
• Although headache is not uncommon in acute stroke, it should alert the physician to the possibility
of other pathologies such as intracerebral haemorrhage (may be insidious and gradually increasing),
subarachnoid haemorrhage (sudden onset with gradual moderation, "most severe headache of my
life"), intracranial hypertension (which may be caused by cerebral venous sinus thrombosis, spaceoccupying lesion), or complicated migraine.
diplopia (common)
• May occur in patients with posterior circulation ischaemia.
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17
DIAGNOSIS
negative symptoms (i.e., loss of function) (common)
Ischaemic stroke
Diagnosis
sensory loss (common)
• Unilateral sensory loss on neurological examination may involve some or all primary modalities.
• Cortical sensory loss usually impairs fine sensory processing abilities such as 2-point discrimination,
graphaesthesia, or stereognosis.
dysarthria (common)
• This sign may accompany facial weakness or cerebellar dysfunction and is usually due to posterior
circulation ischaemia, but may be due to a lacunar infarct.
ga ze paresis (common)
• Often horizontal and unidirectional.
• More common with anterior circulation strokes.
• Wrong-way eye deviation (i.e., gaze deviation away from the side of the brain lesion, towards the
hemiparetic side) should prompt consideration of seizure but can also occur with strokes affecting the
pons or thalamus.
• Horner's syndrome suggests ipsilateral carotid dissection.
arrhythmias, murmurs, or pulmonary oedema (common)
• Associated with cardiac comorbidities, which predispose patients to stroke disease.
• Of particular significance is atrial fibrillation, which increases the patient’s risk for cardioembolic
ischaemic stroke. Therefore, all stroke patients should be assessed for this particular cardiac
arrhythmia with routine non-invasive monitoring and in all eligible patients extended monitoring should
be offered after stroke to increase the chance of detection of paroxysmal atrial fibrillation and earlier
initiation of treatment with anticoagulants.[54]
DIAGNOSIS
vertigo/dizziness (uncommon)
• This is a symptom of posterior circulation ischaemia. Although typically reported as a spinning
sensation, a feeling like being on a ship in choppy seas also describes vertigo.
• It is often associated with nystagmus.
nausea and/or vomiting (uncommon)
• This symptom may be due to posterior circulation ischaemia, or reflect increased intracranial pressure.
neck or facial pain (uncommon)
• May be associated with arterial dissection.
miosis, ptosis, and facial anhidrosis (hemilateral) (uncommon)
• Horner's syndrome may be associated with posterior circulation strokes.
altered level of consciousness/coma (uncommon)
• Reduced level of alertness may accompany large anterior circulation, thalamic, bihemispheric, or brain
stem strokes.
• This sign should prompt a higher level of urgency from both diagnostic (rule out haemorrhage) and
management (breathing and airway protection) points of view.
• Coma is more common with brain stem ischaemia.
• Other conditions mimicking stroke, such as seizures, should be ruled out in these patients.
confusion (uncommon)
18
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Diagnosis
Ischaemic stroke
• This is common, especially in older people with previous strokes or cognitive dysfunction.
• Receptive (Wernicke's) aphasia should be differentiated from confusion, because aphasia is a specific
sign of dominant-hemisphere ischaemia.
Diagnostic tests
1st test to order
Test
Result
CT head
hypoat tenuation
(darkness) of the brain
parenchyma; loss of
grey mat ter-white mat ter
differentiation, and
sulcal effacement;
hyperat tenuation
(brightness) in an artery
indicates clot within the
vessel lumen
• All patients with transient ischaemic attack or possible ischaemic
stroke should initially undergo a CT scan of the brain to rule out
intracranial haemorrhage.
[Fig-3]
• Most important test, needed to differentiate haemorrhagic from
ischaemic stroke. This test is used mainly to rule out haemorrhage
rather than to diagnose stroke, as an essential step in acute stroke
therapy.[55]
• In many cases, the CT is normal within the first few hours of an
ischaemic stroke.[56]
MRI brain
• MRI of the brain, particularly with diffusion-weighted and gradientecho sequences, provides more accurate information about the
stroke lesion compared with CT, clearly highlights the area of
ischaemic infarct, and may provide further clues about the cause(s).
[Fig-2]
acute ischaemic infarct
appears bright on
diffusion-weighted
imaging; at later stages,
T2 images may also show
increased signal in the
ischaemic territory
serum glucose
• To exclude hypoglycaemia as a cause for focal neurological signs.
• Hyperglycaemia has been associated with poor outcome[58] and risk
of haemorrhagic transformation of ischaemic stroke.[59] [60]
• Every patient with transient ischaemic attack or stroke should be
screened for diabetes mellitus by measuring fasting plasma glucose
or haemoglobin A1c, or with an oral glucose tolerance test.[61]
serum electrolytes
• To exclude electrolyte disturbance as a cause for focal neurological
signs.
DIAGNOSIS
[Fig-1]
• However, in many medical centres around the world, MRI is not
available.
• Has higher sensitivity for infarction and equivalent sensitivity for
haemorrhage compared with CT.[57]
• Contraindicated in patients with certain metallic implants such as
pacemakers.
• Some specialised stroke centres are using MRI as the initial imaging
of choice, replacing CT.
• May be implemented in the sub-acute phase after CT in some
centres.
may exclude hypo/
hyperglycaemia
may exclude electrolyte
disturbance
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19
Diagnosis
Ischaemic stroke
Test
Result
serum urea and creatinine
may exclude renal failure
• Renal failure may be a potential contraindication to some stroke
interventions.
cardiac enzymes
• Stroke may be associated with concomitant myocardial infarction.
ECG
• Performed to exclude cardiac arrhythmia or ischaemia, which are
relatively common in ischaemic stroke.
• Present diagnostic protocols suggest a minimum of 24 hours of ECG
monitoring after an ischaemic stroke to exclude atrial fibrillation.
However, it has been found that ECG monitoring along with insertable
cardiac monitor was superior to conventional ECG monitoring in
diagnosing atrial fibrillation in cases of cryptogenic stroke.[49]
• In addition, one significant issue is that in patients with cryptogenic
stroke or transient ischaemic attack who are 55 years old or older,
non-invasive ambulatory ECG with a target of 30 days should
be utilised because this enables clinicians to diagnose and treat
paroxysmal atrial fibrillation.[50]
FBC
• Used to detect conditions that may be potential contraindications for
some acute stroke treatments and interventions. Excludes anaemia
or thrombocytopenia prior to possible initiation of thrombolytics,
anticoagulants, or antithrombotics.
prothrombin time and PTT (with international normalised ratio)
may exclude myocardial
infarction
may exclude arrhythmia or
ischaemia
may exclude anaemia and
thrombocytopenia
may show coagulopathy
DIAGNOSIS
• If patient has no history of anticoagulant use, or of coagulopathy or a
condition that may lead to it, then thrombolysis does not need to be
delayed until the test results are available.[51]
Other tests to consider
Test
Result
serum toxicology screen
may exclude alcohol and
drug abuse
• Performed in selected patients if suspicion of ingestion of toxic
substances. Signs and symptoms may mimic stroke.
CXR
• In the presence of cardiopulmonary signs or symptoms, a CXR can
detect other relevant conditions.
CT or magnetic resonance angiography
• CT angiography preferably, or magnetic resonance angiography,
should be performed in all patients with acute ischaemic stroke and
suspicion of a large vessel occlusion who would be candidates for
endovascular thrombectomy.
20
normal; or cardiomegaly,
aortic dissection,
pneumonia
identifies arterial
occlusion or stenosis
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Diagnosis
Ischaemic stroke
Test
Result
CT or magnetic resonance venography
identifies venous infarcts
• If routine imaging studies fail to show arterial occlusion, and if the
infarct imaging and clinical presentation show characteristics of
venous stroke (e.g., ischaemic tissue not conforming to a vascular
territory, severe haemorrhagic transformation and/or oedema,
intractable seizures at presentation, signs of increased intracranial
pressure), then patency of cerebral venous sinuses can be assessed
by CT or MR venography.
carotid ultrasound
• More frequently performed in the sub-acute stage to investigate for
carotid stenosis.
transcranial Doppler ultrasound
• May be used to identify arterial occlusion of the major arterial
branches of the circle of Willis.
• Spatial resolution is limited compared with CT and magnetic
resonance angiography.
conventional (invasive) angiography
• Not typically indicated in acute stroke unless a simultaneous
endovascular intervention, such as intra-arterial thrombolysis or clot
retrieval, is contemplated.
identifies cervical artery
occlusion or critical
stenosis
may reveal intracranial
artery occlusion or
critical stenosis
vascular occlusion or
stenosis, vasculitis,
arterial dissection,
reversible cerebral
vasoconstriction
syndrome, Moyamoya
disease (vascular
occlusion affecting circle
of Willis), fibromuscular
dysplasia
Emerging tests
Result
CT- or MRI-perfusion-weighted imaging
identifies cerebral
regions with reduced
blood flow that may be
at risk for subsequent
infarction
• Has been proposed as a means of selecting patients, presenting
beyond 4.5 hours, who have hypoperfused but still viable tissue.
• These imaging methods are promising but have not yet been fully
validated for patient selection for re-perfusion therapies.[52]
[Fig-4]
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DIAGNOSIS
Test
21
Diagnosis
Ischaemic stroke
Differential diagnosis
DIAGNOSIS
Condition
Differentiating signs / Differentiating tests
symptoms
Intracerebral
haemorrhage
• No symptoms or signs
reliably distinguish
haemorrhagic stroke from
ischaemic stroke.
• Haemorrhagic stroke is
more often associated
with reduced level of
consciousness and signs
of increased intracranial
pressure than ischaemic
stroke.
•
CT or MRI demonstrates
haemorrhage
(hyperattenuation).
Transient ischaemic
at tack
• Transient neurological
symptoms last less than 24
hours, with no evidence of
acute infarct.
•
CT or MRI may be normal or
may reveal evidence of older
infarcts.
Hypertensive
encephalopathy
• The combination of
headache, cognitive
abnormalities or decreased
level of consciousness,
and hypertension
significantly above patient's
baseline blood pressure
indicates hypertensive
encephalopathy. Other
possible signs/symptoms
include visual changes or
loss, or signs of increased
intracranial pressure.[46]
•
Cerebral oedema on CT or
MRI.
Hypoglycaemia
• There may be a history of
diabetes with use of insulin
or insulin secretagogues.
• Decreased level of
consciousness.
•
Low serum glucose at time
of symptoms.
22
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Diagnosis
Ischaemic stroke
Condition
Differentiating signs / Differentiating tests
symptoms
• Repetitive history of similar
events; preceding aura,
headache in a marching
pattern differentiates
complicated migraine.[46]
• Stroke often presents with
negative symptoms (e.g.,
visual loss, numbness, or
weakness).
• Positive symptoms (e.g.,
marching paraesthesias,
visual hallucinations,
and abnormal motor
manifestations) are more
likely with complicated
migraine.
•
MRI shows no evidence of
infarction.
Seizure and postictal
deficits
• Hx seizures; witnessed
seizure followed by postictal
deficits: for example,
drowsiness and tonguebiting.[46]
• Wrong-way eye deviation
(i.e., gaze deviation
away from the side of the
brain lesion, towards the
hemiparetic side) should
prompt consideration of
seizure but can also occur
with strokes affecting the
pons or thalamus.
•
Electroencephalogram
confirms evidence of seizure.
MRI shows no evidence of
infarction.
Conversion and
somatisation disorders
• Neurological signs and
symptoms do not fit a
vascular territory.
• No cranial nerve deficits.
• Additionally, conversion
disorder displays multiple
signs that are neurologically
inconsistent.
•
MRI shows no evidence of
infarction.
Wernicke's
encephalopathy
• History of alcohol abuse.
• Irritability, confusion, and
delirium common presenting
features.
•
Decreased blood thiamine
level and successful
therapeutic trial of thiamine.
Brain tumour
• Symptoms and signs more
likely to have been on-going.
• May be history of cancer if
metastatic lesion causing
symptoms.
•
CT head demonstrates
lesion or lesions.
•
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DIAGNOSIS
Complicated migraine
23
Ischaemic stroke
Treatment
Step-by-step treatment approach
The goals of treatment of acute ischaemic stroke are to restore blood flow, support energy metabolism
in ischaemic tissue, treat complications of stroke-related oedema, and prevent common acute medical
complications. Rapid evaluation and diagnosis is the cornerstone of successful ischaemic stroke therapy.
Computed tomography (CT) or magnetic resonance imaging (MRI) scan is mandatory to exclude
intracerebral haemorrhage and stroke mimics. The absence of signs on CT does not exclude acute
ischaemic stroke. Following assessment of airway, breathing, and circulation, the next step is to consider
whether reperfusion can be achieved.
Intravenous thrombolysis
Alteplase, a recombinant tissue plasminogen activator (r-tPA), promotes thrombolysis and thereby
re-canalisation and re-perfusion. Early administration of alteplase to appropriate patients is
recommended.[51] Results of clinical trials utilising alteplase for thrombolysis in patients with acute
ischaemic stroke and no contraindications have suggested that the window of opportunity for treatment
of these patients is 4.5 hours after the onset of neurological symptoms.[51] [62] [63] 1[A]Evidence Early
treatment is especially important in patients with severe acute stroke.[64] Goal time between emergency
department arrival and start of CT scan is 25 minutes, and from emergency department arrival to initiation
of intravenous r-tPA (if indicated) is 60 minutes.[46]
Information regarding the benefits and risks of r-tPA treatment should be given to the patient, if
competent, or to a surrogate decision-maker, if present. Verbal or written consent should be obtained
if feasible. In the frequent situation where the patient is not competent to make medical decisions, and
family or a surrogate decision-maker cannot be identified or approached in a timely manner, the physician
should substitute his or her judgement. Decision-makers should be informed of the overall 6% risk of
brain haemorrhage, of which approximately half are fatal. They should also be informed that despite this
risk people treated with r-tPA are more likely to do better. Overall 1 in 8 people treated with r-tPA have a
complete or near-complete recovery who otherwise would have been disabled; this statistic is the number
needed to treat.[65]
Contraindications to intravenous thrombolysis with r-tPA
The following are contraindications to r-tPA treatment from the American Heart Association/American
Stroke Association (AHA/ASA) guidelines:[51]
TREATMENT
•
•
•
•
•
•
•
•
•
•
•
24
Onset of symptoms >4.5 hours
CT reveals acute acute intracranial haemorrhage
There is history of head trauma or prior stroke in the previous 3 months
There is history of previous intracranial haemorrhage
There is history of intracranial/intraspinal surgery within 3 months
The symptoms of stroke are suggestive of subarachnoid haemorrhage
Patients with platelets <100 000/mm3, international normalised ratio (INR) >1.7, activated PTT
(aPTT) >40 seconds, or prothrombin time >15 seconds
There is history of gastrointestinal malignancy or recent bleeding event in the previous 21 days
There is history of major surgery or serious trauma in the previous 14 days
Patient has received a dose of low-molecular-weight heparin within the previous 24 hours
Patient is taking direct thrombin inhibitors or direct factor Xa inhibitors unless laboratory tests such
as aPTT, INR, platelet count, ecarin clotting time, thrombin time, or appropriate direct factor Xa
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Ischaemic stroke
•
•
•
•
•
Treatment
activity assays are normal or the patient has not received a dose of these agents for >48 hours
(assuming normal renal metabolising function)
There is evidence of active bleeding on examination
There are symptoms consistent with infective endocarditis
There is known or suspected association between the acute ischaemic stroke and aortic arch
dissection
Patient is taking antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor
There is history of an intra-axial intracranial neoplasm.
Candidates for intravenous thrombolysis with r-tPA
The AHA/ASA guidelines state that the eligibility recommendations for treating with r-tPA are:[51]
• Within 3 hours or patient last known well or at baseline state:
• Medically eligible patients ≥18 years of age or <80 and >80 years of age
• Patients with severe stroke symptoms or mild but disabling stroke symptoms
• Within 3 to 4.5 hours or patient last known well:
•
•
•
•
•
Patients ≤80 years of age
Those without a history of both diabetes mellitus and stroke
Those with a baseline National Institutes of Health (NIH) Stroke Scale score ≤25
Those not taking any oral anticoagulants
Those without imaging evidence of ischaemic injury involving more than one third of the
middle cerebral artery territory
• Patients whose blood pressure can be lowered safely to <185/110 mmHg with antihypertensive
agents
• Patients with initial glucose levels >2.8 mmol/L (>50 mg/dL)
• Patients with early ischaemic changes on non-contrast computed tomography of mild to moderate
extent (other than frank hypodensity)
• Patients who have had antiplatelet monotherapy or combination therapy before stroke, provided
the benefit of alteplase outweighs the possible increased risk of symptomatic intracerebral
haemorrhage
• Patients with end-stage renal disease on haemodialysis and normal aPTT.
Additional recommendations for treatment with r-tPA can be found in the AHA/ASA guidelines.[51]
Administration of r-tPA should not be delayed by additional tests unless a specific contraindication
is suspected and must be ruled out. Blood glucose should be normalised before initiating r-tPA
treatment.[51]
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25
TREATMENT
Caution should be exercised in treating a patient with major deficits, as the likelihood of favourable
outcome is reduced and there is increased risk of haemorrhage following thrombolysis in these
patients.[51] [66] A meta-analysis found that patients aged 80 years or over presenting with new-onset
neurological deficits, who are also candidates for r-tPA, appear to have a lower probability of a favourable
outcome and a higher mortality rate compared with younger patients. However, the rate of symptomatic
intracranial haemorrhage was not significantly increased.[67]
Ischaemic stroke
Treatment
Aspirin
Ischaemic stroke patients should receive aspirin.[51] Aspirin should be given to patients who have
received r-tPA and to those who are not eligible for r-tPA. However, if r-tPA is administered, aspirin
should not be started for 24 hours, and only then after a head CT shows the absence of intracranial
haemorrhage.[51] [68] Although studies of aspirin for acute ischaemic stroke have shown a trend
towards better outcomes in the aspirin arm,[69] [70] a study examining early (i.e., within 24 hours)
administration of aspirin in acute ischaemic stroke patients receiving r-tPA did not show any significant
improvements in outcomes at 3 months.[68] Furthermore, early administration of aspirin was associated
with a significant increase in risk of symptomatic intracerebral bleeding. Non-aspirin antiplatelet drugs,
including dipyridamole, clopidogrel, and platelet glycoprotein IIb/IIIa inhibitors, have not been studied
in acute stroke and, therefore, in general are not indicated. However, these medicines are useful in the
secondary prevention of stroke.[71]
Endovascular interventions
In certain carefully selected patients with acute ischaemic stroke, use of endovascular interventions in
addition to intravenous r-tPA can provide clinical benefits. As is the case with intravenous r-tPA, initiation
of endovascular interventions should be carried out as early as possible. Initiation within the first 6 hours
of ischaemic stroke onset is likely to result in a more favourable outcome with these interventions.[51]
Endovascular interventions include intra-arterial thrombolysis and mechanical clot-removing devices,
such as stent retrievers. The AHA/ASA guidelines recommend the use of stent retrievers over intraarterial thrombolysis and other mechanical thrombectomy devices (e.g., concentric retrievers) as firstline endovascular therapy for acute ischaemic stroke; however, devices other than stent retrievers may
be reasonable in some circumstances.[51] The use of a proximal balloon guide catheter or large bore
distal catheter, rather than a cervical guide catheter alone, in conjunction with stent retrievers may also be
useful in certain carefully selected patients.[51] Furthermore, it may be reasonable to use an adjunctive
intervention (e.g., intra-arterial thrombolysis) to achieve acceptable reperfusion, if it is used within 6 hours
of symptom onset.
Candidates for endovascular interventions
The AHA/ASA guidelines state that patients who are eligible for r-tPA should be treated with r-tPA even if
they are potential candidates for endovascular therapy with a stent retriever.[51] Observing patients for a
clinical response to intravenous r-tPA prior to use of endovascular therapy is not required.
TREATMENT
The AHA/ASA guidelines suggest that patients who meet all of the following criteria should be treated with
a stent retriever:[51]
•
•
•
•
•
•
Have a pre-stroke modified Rankin disability scale score 0 to 1
Have causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1)
Aged ≥18 years
Have a NIH Stroke Scale score ≥6
Have an Alberta Stroke Program Early CT score (ASPECTS) ≥6
Can begin endovascular therapy (groin puncture) within 6 hours of symptom onset.
Although there is a lack of evidence for stent retrievers in ischaemic stroke patients outside of these
criteria, they may be considered for use in those with anterior circular occlusion who cannot be treated
with intravenous r-tPA, or those with occlusion of other vessels, such as the M2 or M3 portion of the
middle cerebral artery, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral
26
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BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Ischaemic stroke
Treatment
arteries. They may also be considered for patients who are aged <18 years, or have a modified Rankin
disability scale score >1, or an ASPECTS <6, if initiated within 6 hours of symptom onset, but the potential
benefits are unclear as there is a lack of evidence in these patients.
Initial treatment with intra-arterial thrombolysis may be considered for carefully selected patients with
major ischaemic strokes of <6 hours’ duration with causative occlusion of the middle cerebral artery,[72]
or those with contraindications or an incomplete response to r-tPA. However, the evidence for intra-arterial
thrombolysis is weak, and there are no intra-arterial thrombolytic interventions approved for use in stroke.
Anticoagulation
Urgent anticoagulation in unselected ischaemic stroke patients, with the goal of improving acute stroke
outcomes, is generally not recommended. Meta-analyses fail to show reduction in stroke disability
in acute ischaemic stroke patients treated with anticoagulants but do show an increase in the risk of
haemorrhagic transformation of stroke, particularly in patients with larger stroke volumes.[73]
There is still inadequate evidence to guide treatment decisions about the optimal time of anticoagulation
treatment in patients with acute transient ischaemic attack or ischaemic stroke and an indication for
anticoagulation. Some experts suggest to initiate anticoagulation in atrial fibrillation patients between 1
and 12 days after an ischaemic stroke, depending on stroke severity, using the 1-3-6-12 days approach
with re-institution of anticoagulation in patients with:[74]
•
•
•
•
Transient ischaemic attack: 1 day after acute event
Small, non-disabling infarct: 3 days after acute event
A moderate stroke: 6 days after acute event
Large infarcts involving large parts of the arterial territory: 12 days after acute event.
Anticoagulation is, however, first-line therapy for cerebral venous sinus thrombosis (as identified on
imaging), even in the presence of haemorrhagic transformation of the infarction.[66] Anticoagulation
should be continued for 3 to 6 months. In the absence of progressive symptoms, patients may be
transitioned to warfarin in the acute period, with target INR 2.0 to 3.0. Aspirin and r-tPA are not indicated
in these patients.
Supportive care
At the same time as the acute evaluation for reperfusion therapies, the following steps should be taken:
• Support blood oxygenation. Supplemental oxygen should be provided only when blood oxygen
saturation is <94%. Liberal use of oxygen is associated with increased mortality in acutely ill
patients.[75] Patients with decreased level of consciousness or refractory hypoxaemia may require
intubation with mechanical ventilation.[51] [76]
[VIDEO: Tracheal intubation animated demonstration ]
[VIDEO: Bag-valve-mask ventilation animated demonstration ]
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BMJ Best Practice topics are regularly updated and the most recent version
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27
TREATMENT
• Support systemic blood pressure (BP). Management of arterial BP in acute ischaemic stroke
remains controversial because of conflicting evidence and a lack of large controlled clinical trials.
Many patients with ischaemic stroke have elevated BP at presentation. Lowering BP could reduce
cerebral perfusion pressure and promote stroke extension.[80]
• Normalise blood glucose levels. Hypoglycaemia can cause brain injury and should be avoided.
Hyperglycaemia has been associated with poor outcome[58] and risk of haemorrhagic
Ischaemic stroke
Treatment
transformation of ischaemic stroke.[59] [60] Treatment of significantly elevated blood glucose is
recommended despite inconclusive evidence.[81] [82] [83]
• Reduce fever. Fever has been associated with worse stroke outcome.[84] Treatment of fever is
therefore reasonable, although not yet shown to be effective by controlled trials.[51] [85] [86] [87]
These steps, while not shown to be effective by clinical trials, may retard stroke evolution or prevent stroke
extension by optimising energy substrate delivery and tissue energy metabolism.
Following emergency department evaluation and treatment, patients with ischaemic stroke should be
transferred to a dedicated stroke unit. These units have been shown in controlled and non-controlled trials
to improve stroke functional outcome and survival.[88] Stroke units should have multi-disciplinary teams
which include physicians, nursing staff, and rehabilitation specialists with expertise in stroke. Improved
supportive care, avoidance of complications such as infection, and earlier initiation of rehabilitation
therapy are among the mechanisms by which stroke units are hypothesised to produce better outcomes.
Nutritional support, rehabilitation therapy (physical, occupational, and/or speech therapy as indicated),
prevention of aspiration (swallowing assessment), and prevention of venous thromboembolism (VTE) are
all required in the sub-acute phase of hospital care.
Swallowing impairment is common in stroke and is associated with an increased risk of aspiration
pneumonia[89] and death.[90] Guidelines support the use of a bedside swallow test before eating or
drinking but do not provide specifics on test administration and interpretation.[51] A reasonable approach
is to withhold oral intake if there is coughing or a wet voice after swallowing a small cup of water. Patients
who cannot take nutrition orally should be hydrated with isotonic fluids (to decrease risk of brain oedema)
and receive enteral feeding by nasogastric, nasoduodenal, or percutaneous gastrostomy tube.
VTE is the cause of about 10% of stroke deaths.[91] VTE prophylaxis should be provided to nonambulatory stroke patients, even though most of the evidence for VTE prophylaxis comes from
controlled trials in non-stroke populations.[92] Anticoagulants should be used except when haemorrhagic
transformation is present, in which case pneumatic compression devices may be used instead.[93]
Early mobilisation of patients is also recommended in stroke patients. This may decrease risk of venous
thromboembolism by reducing venous stasis, but this has not been demonstrated in controlled trials.[94]
There is insufficient evidence to recommend the use of drugs that affect nitric oxide production (ie., nitric
oxide donors, L-arginine, or nitric oxide synthase inhibitors) in acute stroke.[95] A Cochrane review has
shown that cerebrolysin, a mixture of peptides derived from pig brain tissue, performs no better than
placebo in terms of all-cause death when given to people with acute ischaemic stroke within 48 hours
of stroke onset. There are also concerns about the increase of serious adverse events with cerebrolysin
use in people with acute ischaemic stroke.[96] While it is commonly used in some countries (e.g., China,
Russia), it is not available in other locations, including the US, Europe, and the UK.
TREATMENT
Treatment details overview
Consult your local pharmaceutical database for comprehensive drug information including contraindications,
drug interactions, and alternative dosing. ( see Disclaimer )
Acute
28
( summary )
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Treatment
Ischaemic stroke
Acute
( summary )
without cerebral venous sinus
thrombosis
presentation within
4.5 hours and no
contraindication to
thrombolysis
1st
adjunct
aspirin 24 hours after r-tPA
adjunct
endovascular intervention (stent retriever)
plus
supportive care
plus
swallowing assessment
adjunct
presentation after 4.5
hours or contraindication
to thrombolysis
alteplase (recombinant tissue
plasminogen activator or r-tPA)
1st
VTE prophylaxis + early mobilisation
aspirin
plus
supportive care
plus
swallowing assessment
adjunct
VTE prophylaxis + early mobilisation
with cerebral venous sinus
thrombosis
1st
anticoagulation
plus
supportive care
plus
swallowing assessment
TREATMENT
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BMJ Best Practice topics are regularly updated and the most recent version
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29
Treatment
Ischaemic stroke
Treatment options
Acute
without cerebral venous sinus
thrombosis
presentation within
4.5 hours and no
contraindication to
thrombolysis
1st
alteplase (recombinant tissue
plasminogen activator or r-tPA)
Primary options
» alteplase: 0.9 mg/kg total dose
intravenously, administer 10% of dose as a
bolus, with the remaining 90% infused over 1
hour, maximum 90 mg total dose
» Intravenous alteplase (r-tPA) promotes
thrombolysis, which may result in reperfusion of
ischaemic but still salvageable brain tissue.
» Results of clinical trials utilising alteplase for
thrombolysis in patients with acute ischaemic
stroke and no contraindications suggest that
the window of opportunity for treatment of
these patients is 4.5 hours after the onset
of neurological symptoms.[51] [62] [63]
1[A]Evidence Early treatment is especially
important in patients with severe acute
stroke.[64] In the frequent situation where the
onset of symptoms was not witnessed, the
time of onset must be presumed to be the time
at which the patient was last witnessed to be
normal.
» Criteria for use include measurable
neurological deficit and positive computed
tomography head; no recent history of head
trauma, myocardial infarction, gastrointestinal or
urinary tract haemorrhage; no recent surgery;
no previous history of intracranial haemorrhage;
acceptable blood pressure, platelet count,
international normalised ratio, and glucose
levels; no seizures.
» Guidelines from the American Heart
Association/American Stroke Association (AHA/
ASA) state that the eligibility recommendations
for treating with r-tPA are:[51]
TREATMENT
» Within 3 hours or patient last known well or
at baseline state: medically eligible patients
≥18 years of age or <80 and >80 years of age;
severe stroke symptoms or mild but disabling
stroke symptoms.
» Within 3 to 4.5 hours or patient last known
well: patients ≤80 years of age; those without
30
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Treatment
Ischaemic stroke
Acute
a history of both diabetes mellitus and stroke;
those with a baseline National Institutes of
Health Stroke Scale score ≤25; those not taking
any oral anticoagulants; those without imaging
evidence of ischaemic injury involving more than
one third of the middle cerebral artery territory.
» Additional recommendations for treatment
with r-tPA can be found in the AHA/ASA
guidelines.[51]
» Cerebral venous sinus thrombosis is a
contraindication, and orolingual oedema is a rare
but potentially serious complication.
adjunct
aspirin 24 hours after r-tPA
Primary options
» aspirin: 300 mg orally once daily
» Ischaemic stroke patients should receive
aspirin.[51] Patients who are administered
alteplase (r-tPA) should not start aspirin for 24
hours after r-tPA, and only then after a head
computed tomography shows the absence of
intracranial haemorrhage.[51] [68] [97]
» Two randomised trials of aspirin for acute
ischaemic stroke have shown a trend towards
better outcomes in the aspirin arm.[69] [70]
» Non-aspirin antiplatelet drugs, including
dipyridamole, clopidogrel, and platelet
glycoprotein IIb/IIIa inhibitors, have not been
studied in acute stroke and therefore in general
are not indicated. However, these drugs may be
useful in the secondary prevention of stroke.[71]
adjunct
endovascular intervention (stent retriever)
» Initiation of endovascular interventions should
be carried out as early as possible, ideally within
the first 6 hours of ischaemic stroke onset.
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BMJ Best Practice topics are regularly updated and the most recent version
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31
TREATMENT
» Stent retrievers used in conjunction with
intravenous r-tPA can provide clinical benefits
in certain carefully selected patients with
acute ischaemic stroke.[98] [99] [100] [101]
[102] [103] [104] [105] The American Heart
Association/American Stroke Association
recommends the use of stent retrievers over
intra-arterial thrombolysis and other mechanical
thrombectomy devices (e.g., concentric
retrievers) as first-line endovascular therapy for
acute ischaemic stroke; however, devices other
than stent retrievers may be reasonable in some
circumstances.[51]
Treatment
Ischaemic stroke
Acute
» Patients meeting all of the following criteria
can be treated with a stent retriever: have a prestroke modified Rankin disability scale score 0
to 1; have causative occlusion of the internal
carotid artery or proximal middle cerebral artery
(M1); aged ≥18 years; have a National Institutes
of Health Stroke Scale score ≥6; have an Alberta
Stroke Program Early CT score (ASPECTS)
≥6; and can begin endovascular therapy (groin
puncture) within 6 hours of symptom onset.[51]
» Stent retrievers may be considered for
ischaemic stroke patients outside of these
criteria if used within 6 hours of symptom
onset: for example, patients with anterior
circular occlusion who cannot be treated with
intravenous r-tPA; those with occlusion of other
vessels such as the M2 or M3 portion of the
middle cerebral artery, anterior cerebral arteries,
vertebral arteries, basilar artery, or posterior
cerebral arteries; or those with an ASPECTS
<6.[51] However, this is not supported by
evidence.
» Proximal balloon guide catheter or a large
bore distal catheter, rather than a cervical
guide catheter alone, in conjunction with stent
retrievers may also be useful in certain carefully
selected patients.[51] An adjunctive intervention
(e.g., intra-arterial thrombolysis) may also be
useful to achieve acceptable reperfusion, if
it is used within 6 hours of symptom onset.
However, there are no intra-arterial thrombolytic
interventions approved for use in stroke.
plus
supportive care
» Controlled clinical trials have shown that
admission to a dedicated stroke unit, in
comparison to admission to a general medical/
surgical service, is associated with improved
survival and less disability at 1 year.[88]
Stroke units should include multi-disciplinary
teams including physicians, nursing staff,
and rehabilitation specialists with expertise in
stroke. Improved supportive care, avoidance
of complications such as infection, and earlier
initiation of rehabilitation therapy are among
the mechanisms by which stroke units are
hypothesised to produce better outcomes.
TREATMENT
» Supplemental oxygen should be provided
ONLY when blood oxygen saturation is <94%.
Liberal use of oxygen is associated with
increased mortality in acutely ill patients.[75]
Patients with decreased level of consciousness
or refractory hypoxaemia may require intubation
with mechanical ventilation.[51] [76]
32
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BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Treatment
Ischaemic stroke
Acute
[VIDEO: Tracheal intubation
animated demonstration ]
[VIDEO: Bag-valve-mask ventilation
animated demonstration ]
» Management of arterial blood pressure (BP)
in acute ischaemic stroke remains controversial
because of conflicting evidence and a lack of
large controlled clinical trials. Many patients
with ischaemic stroke have elevated BP at
presentation. Lowering BP could reduce
cerebral perfusion pressure and promote stroke
extension.[80]
» Hypoglycaemia can cause brain injury and
should be avoided. Hyperglycaemia has been
associated with poor outcome[58] and risk
of haemorrhagic transformation of ischaemic
stroke.[59] [60] Treatment of significantly
elevated blood glucose is recommended despite
inconclusive evidence.[81] [82] [83]
» Fever has been associated with worse stroke
outcome.[84] Treatment of fever is therefore
reasonable, although not yet shown to be
effective by controlled trials.[51] [85] [86] [87]
plus
swallowing assessment
» Swallowing impairment is common in stroke
and is associated with an increased risk of
aspiration pneumonia[89] and death.[90]
Guidelines support the use of a bedside
swallow test before eating or drinking but do
not provide specifics on test administration and
interpretation.[51]
» A reasonable approach is to withhold oral
intake if there is coughing or a wet voice after
swallowing a small cup of water.
» Patients who cannot take nutrition orally should
receive fluids and enteral feeding by nasogastric,
nasoduodenal, or percutaneous gastrostomy
tube.
adjunct
VTE prophylaxis + early mobilisation
Primary options
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BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
33
TREATMENT
» heparin: 5000 units subcutaneously every
12 hours
-or» dalteparin: 5000 units subcutaneously once
daily
-or» enoxaparin: 40 mg subcutaneously once
daily
Treatment
Ischaemic stroke
Acute
-or» pneumatic compression devices
--AND-» early mobilisation
» Venous thromboembolism (VTE) is the cause
of about 10% of stroke deaths.[91]
» Prophylaxis against VTE should be provided
to non-ambulatory stroke patients; efficacy data
come predominantly from controlled trials in nonstroke populations.[92]
» VTE prophylaxis may include heparins and
pneumatic compression devices.[94]
» Early mobilisation of patients is recommended,
but efficacy has not been demonstrated in
controlled trials. May decrease risk of venous
thromboembolism by reducing venous stasis.
presentation after 4.5
hours or contraindication
to thrombolysis
1st
aspirin
Primary options
» aspirin: 300 mg orally once daily
» Ischaemic stroke patients should receive
aspirin.[51]
» Two randomised trials of aspirin for acute
ischaemic stroke have shown a trend towards
better outcomes in the aspirin arm.[69] [70]
» Non-aspirin antiplatelet drugs, including
dipyridamole, clopidogrel, and glycoprotein
IIb/IIIa inhibitors, have not been studied in
acute stroke and therefore in general are not
indicated. However, these drugs are useful in the
secondary prevention of stroke.[71]
plus
supportive care
TREATMENT
» Controlled clinical trials have shown that
admission to a dedicated stroke unit, in
comparison to admission to a general medical/
surgical service, is associated with improved
survival and less disability at 1 year.[88]
Stroke units should include multi-disciplinary
teams including physicians, nursing staff,
and rehabilitation specialists with expertise in
stroke. Improved supportive care, avoidance
of complications such as infection, and earlier
initiation of rehabilitation therapy are among
the mechanisms by which stroke units are
hypothesised to produce better outcomes.
» Supplemental oxygen should be provided
ONLY when blood oxygen saturation is <94%.
34
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BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Treatment
Ischaemic stroke
Acute
Liberal use of oxygen is associated with
increased mortality in acutely ill patients.[75]
Patients with decreased level of consciousness
or refractory hypoxaemia may require intubation
with mechanical ventilation.[51] [76]
» Management of arterial blood pressure (BP)
in acute ischaemic stroke remains controversial
because of conflicting evidence and a lack of
large controlled clinical trials. Many patients
with ischaemic stroke have elevated BP at
presentation. Lowering BP could reduce
cerebral perfusion pressure and promote stroke
extension.[80]
[VIDEO: Tracheal intubation
animated demonstration ]
[VIDEO: Bag-valve-mask ventilation
animated demonstration ]
» Hypoglycaemia can cause brain injury and
should be avoided. Hyperglycaemia has been
associated with poor outcome[58] and risk
of haemorrhagic transformation of ischaemic
stroke.[59] [60] Treatment of significantly
elevated blood glucose is recommended despite
inconclusive evidence.[81] [82] [83]
» Fever has been associated with worse stroke
outcome.[84] Treatment of fever is therefore
reasonable, although not yet shown to be
effective by controlled trials.[51] [85] [86] [87]
plus
swallowing assessment
» Swallowing impairment is common in stroke
and is associated with an increased risk of
aspiration pneumonia[89] and death.[90]
Guidelines support the use of a bedside
swallow test before eating or drinking, but do
not provide specifics on test administration and
interpretation.[51]
» A reasonable approach is to withhold oral
intake if there is coughing or a wet voice after
swallowing a small cup of water.
adjunct
VTE prophylaxis + early mobilisation
Primary options
» heparin: 5000 units subcutaneously every
12 hours
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Oct 18, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
35
TREATMENT
» Patients who cannot take nutrition orally should
receive fluids and enteral feeding by nasogastric,
nasoduodenal, or percutaneous gastrostomy
tube.
Treatment
Ischaemic stroke
Acute
-or» dalteparin: 5000 units subcutaneously once
daily
-or» enoxaparin: 40 mg subcutaneously once
daily
-or» pneumatic compression devices
--AND-» early mobilisation
» Venous thromboembolism (VTE) is the cause
of about 10% of stroke deaths.[91]
» Prophylaxis against DVT should be provided
to non-ambulatory stroke patients; efficacy data
come predominantly from controlled trials in nonstroke populations.[92]
» VTE prophylaxis may include heparins and
pneumatic compression devices.[94]
» Early mobilisation of patients is recommended,
but efficacy has not been demonstrated in
controlled trials. May decrease risk of venous
thromboembolism by reducing venous stasis.
with cerebral venous sinus
thrombosis
1st
anticoagulation
Primary options
» heparin: consult specialist for guidance on
dosing
OR
» warfarin: 2-10 mg orally once daily initially,
adjust according to INR (target 2.0 to 3.0)
» The use of unfractionated intravenous heparin
for venous sinus thrombosis, even in the
presence of haemorrhagic infarction, has been
recommended based on results from small
clinical trials.[66]
» Dosing recommendations are based on
a stroke-specific dosing scale shown to be
superior to usual physician care.[106]
TREATMENT
» Intravenous heparin should be used with
caution because of its known association
with haemorrhagic conversion of ischaemic
stroke.[73]
» Anticoagulation should be continued for 3
to 6 months. In the absence of progressive
36
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BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Treatment
Ischaemic stroke
Acute
symptoms, patients may be transitioned
to warfarin in the acute period, with target
international normalised ratio (INR) 2.0 to 3.0.
» In the event of abrupt neurological change,
obtain head computed tomography and consider
ceasing heparin until haemorrhage is ruled out.
» Aspirin and alteplase (r-tPA) are not indicated
in these patients.
plus
supportive care
» Controlled clinical trials have shown that
admission to a dedicated stroke unit, in
comparison to admission to a general medical/
surgical service, is associated with improved
survival and less disability at 1 year.[88]
Stroke units should include multi-disciplinary
teams including physicians, nursing staff,
and rehabilitation specialists with expertise in
stroke. Improved supportive care, avoidance
of complications such as infection, and earlier
initiation of rehabilitation therapy are among
the mechanisms by which stroke units are
hypothesised to produce better outcomes.
» Supplemental oxygen should be provided
ONLY when blood oxygen saturation is
<94%.Liberal use of oxygen is associated with
increased mortality in acutely ill patients.[75]
Patients with decreased level of consciousness
or refractory hypoxaemia may require intubation
with mechanical ventilation.[51] [76]
[VIDEO: Tracheal intubation
animated demonstration ]
[VIDEO: Bag-valve-mask ventilation
animated demonstration ]
» Management of arterial BP in acute
ischaemic stroke remains controversial
because of conflicting evidence and a lack of
large controlled clinical trials.Many patients
with ischaemic stroke have elevated BP at
presentation. Lowering BP could reduce
cerebral perfusion pressure and promote stroke
extension.[80]
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Oct 18, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
37
TREATMENT
» Hypoglycaemia can cause brain injury and
should be avoided. Hyperglycaemia has been
associated with poor outcome[58] and risk
of haemorrhagic transformation of ischaemic
stroke.[59] [60] Treatment of significantly
elevated blood glucose is recommended despite
inconclusive evidence.[81] [82] [83]
Treatment
Ischaemic stroke
Acute
» Fever has been associated with worse stroke
outcome.[84] Treatment of fever is therefore
reasonable, although not yet shown to be
effective by controlled trials.[51] [85] [86] [87]
plus
swallowing assessment
» Swallowing impairment is common in stroke
and is associated with an increased risk of
aspiration pneumonia[89] and death.[90]
Guidelines support the use of a bedside
swallow test before eating or drinking but do
not provide specifics on test administration and
interpretation.[51]
» A reasonable approach is to withhold oral
intake if there is coughing or a wet voice after
swallowing a small cup of water.
TREATMENT
» Patients who cannot take nutrition orally should
receive fluids and enteral feeding by nasogastric,
nasoduodenal, or percutaneous gastrostomy
tube.
38
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BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
Follow up
Ischaemic stroke
Recommendations
FOLLOW UP
Monitoring
Monitoring parameters for patients on alteplase (recombinant tissue plasminogen activator or r-tPA) as
per American Heart Association/American Stroke Association (AHA/ASA) guidelines:[51]
• Admit the patient to a stroke unit for monitoring
• Perform blood pressure and neurological assessments every 15 minutes during and after
•
•
•
•
intravenous r-tPA infusion for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours
after intravenous r-tPA treatment
If the patient develops severe headache, acute hypertension, nausea, or vomiting, or has a
worsening neurological examination, discontinue the infusion and obtain emergency CT scan
Increase the frequency of BP measurements if a systolic BP is ≥180 mmHg or if a diastolic BP is
≥105 mmHg; administer antihypertensive medicines to maintain BP at or below these levels
Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure
catheters if the patient can be safely managed without them
Obtain a follow-up CT or MRI scan at 24 hours after intravenous r-tPA before starting
anticoagulants or antiplatelet agents.
Further monitoring may be required for secondary prevention of ischaemic stroke. For example, cardiac
monitoring for atrial fibrillation should be carried out at initial assessment and continued throughout
treatment of acute stroke. The AHA/ASA guidelines recommend continuous cardiac monitoring for at
least the first 24 hours after stroke.[51] Further outpatient monitoring may be instituted in patients with
cryptogenic stroke and suspected paroxysmal arrhythmias, particularly if they had a short admission and
brief monitoring.
Patient instructions
Patients are encouraged to continue rehabilitation in a specialised stroke facility. Rehabilitation often
focuses on activities of daily living, mobility skills, communication skills, and psychological functioning,
and over time will help with improvement of initial symptoms.[114] Patients are advised that depression
may occur after stroke and if not treated will interfere with progress; seeking help at the sign of any
key symptoms is important. Lifestyle changes should include referral to smoking and alcohol cessation
programmes as necessary.
[Stroke Association: life after stroke]
All patients who have had ischaemic stroke or transient ischaemic attack who are capable of physical
exercise must be instructed to participate in at least 3 to 4 sessions of moderate to heavy exercise weekly
in order to decrease the risk factors for stroke.[61] Stroke patients with residual disability should be
referred to physiotherapists or cardiac rehabilitation professionals so they can participate in supervised
and goal-oriented rehabilitation.[61]
Complications
Complications
deep venous thrombosis (DVT)
Timeframe
short term
Likelihood
medium
Motor weakness with lack of mobility causes venous stasis in the lower limbs, resulting in DVT.
Anticoagulation will reduce the risk of pulmonary embolism.[92]
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Follow up
Ischaemic stroke
FOLLOW UP
Complications
seizure
Timeframe
short term
Likelihood
low
May occur with anterior circulation stroke affecting the pons or thalamus.
haemorrhagic transformation of ischaemic stroke
short term
low
Haemorrhagic conversion can occur in any ischaemic stroke, but is more common in larger infarcts
and those for which anticoagulation or alteplase (recombinant tissue plasminogen activator) has been
given.[51] Petechial bleeding may be relatively common and is frequently asymptomatic.[51]
r-tPA-related orolingual oedema
short term
low
Orolingual oedema can rarely complicate use of alteplase (recombinant tissue plasminogen activator or rtPA) and can sometimes require intubation for airway protection.
brain oedema and elevated intracranial pressure
short term
low
Patients with large infarctions affecting the cerebellum or middle cerebral artery are at risk of developing
oedema and elevated intracranial pressure. If left unchecked, the oedema compromises blood flow and
causes brain herniation, which is frequently fatal.
Cerebellar swelling from oedema may cause rapid elevations in pressure in the posterior fossa,
pressure on the brainstem anteriorly, upward or downward cerebellar herniation, or acute hydrocephalus
from compression of the fourth ventricle. Symptoms include obtundation, quadriparesis, oculomotor
abnormalities, or new facial palsy. Placement of an external ventricular drain or decompressive surgery
can be life-saving.[111] Transfer of patients with large cerebellar infarction to a hospital with 24-hour
availability of emergency neurosurgical consultation is indicated.
Decompressive hemicraniectomy should be considered for large hemispheric strokes causing deterioration
from mass effect. Consider decompressive hemicraniectomy in patients with large middle cerebral artery
(MCA) infarction covering all or a significant MCA territory (also recognised as malignant MCA ischaemic
infarct), and declining consciousness within 45 hours after stroke onset.[112] [113] In all patients with large
ischaemic infarcts with potential of brain swelling and herniation, neurosurgical consultation with focus
on decompressive hemicraniectomy should be secured. Neurosurgical intervention reduces mortality,
but survivors are frequently left with severe disability and poor quality of life. Surrogate decision-makers
should be made aware of this and the decision to undertake surgery should be made on a case-by-case
basis.
depression
variable
high
Depression is common after stroke, and may warrant treatment with psychotherapy or antidepressant
medicines.[110]
aspiration pneumonia
variable
low
Stroke-related dysphagia results in aspiration and subsequent pneumonia. A dysphagia screen should be
performed in stroke patients prior to oral intake.[51] When aspiration pneumonia occurs, the pneumonia
should be treated with antibiotics and consideration given to whether enteral feeding is indicated.[51]
40
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Ischaemic stroke
Follow up
Prognosis
Common medical complications of stroke include aspiration pneumonia, depression, and deep vein
thrombosis.
A meta-analysis study on the efficacy of physiotherapy following stroke found that a variety of interventions
improved functional outcomes, even when they were applied late after stroke.[108]
Patients receiving recombinant tissue plasminogen activator (rtPA)
These patients are more likely to have a better outcome than non-r-tPA-treated patients, despite the 6% risk
of symptomatic intracranial haemorrhage. The number needed to treat to prevent 1 additional case of strokerelated disability is approximately 8.[65] Newer research suggests that the number needed to treat to 'shift' a
patient 1 point on the modified Rankin disability scale is even lower (i.e., even in patients without complete or
near-complete recovery, r-tPA probably results in less severe disability).[109]
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41
FOLLOW UP
In 2013, a total of 3.3 million individuals died of ischaemic stroke worldwide. Between 1990 and 2010,
ischaemic stroke mortality decreased 37% in high-income countries and 14% in low- and middle-income
countries.[9] Stroke is a leading cause of serious long-term disability in the US.[9] Prognosis of functional
outcome can be reliably performed by well-validated prognostic scores like the ASTRAL score or the
iScore.[107] Intravenous thrombolysis and dedicated stroke units are the only interventions shown to improve
stroke outcome.
Ischaemic stroke
Guidelines
Diagnostic guidelines
Europe
Stroke and transient ischaemic at tack in over 16s: diagnosis and initial
management
Published by: National Institute for Health and Care Excellence
Last published: 2017
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies,
migraine, stroke, and dementias
Published by: European Federation of Neurological Societies
Last published: 2010
GUIDELINES
North America
2018 guidelines for the early management of patients with acute ischemic
stroke
Published by: American Heart Association; American Stroke
Association
Last published: 2018
ACR appropriateness criteria: cerebrovascular disease
Published by: American College of Radiology
Last published: 2016
Summary of evidence-based guideline update: prevention of stroke in
nonvalvular atrial fibrillation
Published by: American Academy of Neurology
Last published: 2014
ACR appropriateness criteria: focal neurologic deficit
Published by: American College of Radiology
Last published: 2012
Treatment guidelines
Europe
Stroke and transient ischaemic at tack in over 16s: diagnosis and initial
management
Published by: National Institute for Health and Care Excellence
Last published: 2017
European Stroke Organisation (ESO) guidelines for prophylaxis for venous
thromboembolism in immobile patients with acute ischaemic stroke
Published by: European Stroke Organisation
Last published: 2016
European Stroke Organisation (ESO) guidelines for the management of
temperature in patients with acute ischemic stroke
Published by: European Stroke Organisation
42
Last published: 2015
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Guidelines
Ischaemic stroke
Europe
Alteplase for treating acute ischaemic stroke
Published by: National Institute for Health and Care Excellence
Last published: 2012
Guidelines for management of ischaemic stroke and transient ischaemic
at tack
Published by: European Stroke Organisation
Last published: 2008
North America
2018 guidelines for the early management of patients with acute ischemic
stroke
Last published: 2018
GUIDELINES
Published by: American Heart Association; American Stroke
Association
Acute stroke management: prehospital, emergency department, and acute
inpatient stroke care
Published by: Acute Stroke Management Best Practice Writing Group;
Canadian Stroke Best Practices and Quality Advisory Committees;
Canadian Stroke Consortium; Canadian Association of Emergency
Physicians
Last published: 2018
Guidelines for adult stroke rehabilitation and recovery
Published by: American Heart Association; American Stroke
Association
Last published: 2016
Summary of evidence-based guideline update: prevention of stroke in
nonvalvular atrial fibrillation
Published by: American Academy of Neurology
Last published: 2014
Guidelines for the prevention of stroke in patients with stroke and transient
ischemic at tack
Published by: American Heart Association; American Stroke
Association
Last published: 2014
Guidelines for the primary prevention of stroke
Published by: American Heart Association
Last published: 2014
Antithrombotic and thrombolytic therapy for ischemic stroke: antithrombotic
therapy and prevention of thrombosis, 9th ed
Published by: American College of Chest Physicians
Last published: 2012
Diagnosis and management of cerebral venous thrombosis
Published by: American Heart Association
Last published: 2011
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43
Guidelines
Ischaemic stroke
North America
Stroke Treatment Academic Industry Roundtable (STAIR) recommendations
for maximizing the use of intravenous thrombolytics and expanding
treatment options with intra-arterial and neuroprotective therapies
Published by: Stroke Treatment Academic Industry Roundtable
Last published: 2011
Updated Society for Vascular Surgery guidelines for management of
extracranial carotid disease
Published by: Society for Vascular Surgery
Last published: 2011
Anticoagulants and antiplatelet agents in acute ischemic stroke
GUIDELINES
Published by: American Academy of Neurology; American Heart
Association
Last published: 2002
Africa
The South African guideline for the management of ischemic stroke and
transient ischemic at tack: recommendations for a resource-constrained
health care set ting
Published by: South African Stroke Society
Last published: 2011
Oceania
Clinical guidelines for stroke management 2017
Published by: National Stroke Foundation (Australia)
44
Last published: 2017
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Ischaemic stroke
Online resources
Online resources
1.
Stroke Association: life after stroke (external link)
ONLINE RESOURCES
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45
Ischaemic stroke
Evidence scores
Evidence scores
EVIDENCE SCORES
1.
46
Clinical outcomes: there is good-quality evidence that r-tPA administered between 3 and 4.5 hours
after the onset of symptoms significantly improved clinical outcomes in patients with acute ischaemic
stroke compared with placebo.[63]
Evidence level A: Systematic reviews (SRs) or randomized controlled trials (RCTs) of >200
participants.
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Ischaemic stroke
References
Key articles
Kannel WB, Wolf PA, Verter J, et al. Epidemiologic assessment of the role of blood pressure in stroke:
the Framingham study. JAMA. 1970 Oct 12;214(2):301-10. Abstract
•
Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients
with acute ischemic stroke: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-110. Full text Abstract
•
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen
activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. Full text Abstract
•
Sandercock PAG, Collins R, Counsell C, et al. The International Stroke Trial (IST): a randomised trial
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•
Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic
•
Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke: the
PROACT II study: a randomized controlled trial. JAMA. 1999 Dec 1;282(21):2003-11. Full text
Abstract
•
Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive surgery in malignant infarction of the
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47
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Images
Images
IMAGES
Figure 1: (A) T2-weighted MRI image showing hyperintense signal representing prolonged T2. Shows
abnormal T2 of 153.38 ms on the left, compared with the normal contralateral side (96 ms). Note that the
lesion is located on the ascending frontal gyrus. (B) Gradient echo images detect haemosiderin compounds
due to magnetic susceptibility of iron. In this case the result is negative
From the personal collection of Eric E. Smith; used with permission
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Images
IMAGES
Ischaemic stroke
Figure 2: (A) Non-contrast T1-weighted MRI. (B) Post-contrast T1-weighted MRI showing minimal increase
in leptomeningeal vessels over the right frontal region. (C) Diffusion-weighted image (DWI) showing a
hyperintense area in the right frontal region. (D) Apparent diffusion coefficient (ADC) map shows hypointense
lesion, indicating restricted diffusion that correlates with high intensity on DWI and exponential diffusion. (E)
ADC value is 0.22 x 10¯³ mm²/second, corresponding to a hyperacute infarct
From the personal collection of Eric E. Smith; used with permission
58
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IMAGES
Figure 3: Non-contrast CT scan of brain showing sub-acute isolated left basal ganglion infarction with left
frontal horn mass effect
Courtesy of BMJ Case Reports 2009; doi:10.1136/bcr.10.2008.1139
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Images
IMAGES
Ischaemic stroke
Figure 4: MRI arterial spin labelling image showing extensive hypoperfusion in the right cerebral hemisphere.
There is a clear mismatch between diffusion and perfusion
From the personal collection of Eric E. Smith; used with permission
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Contributors:
// Authors:
George Ntaios, MD, MSc (ESO Stroke Medicine), PhD, FESO
Assistant Professor of Internal Medicine
Medical School, University of Thessaly, Secretary General, Hellenic Stroke Organization, Larissa University
Hospital, Larissa, Greece
DISCLOSURES: GN is on the advisory boards for, and has received honoraria, speaker fees, and research
support from: Amgen, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Elpen, Galenica, Medtronic, Sanofi, and
Winmedica.
// Acknowledgements:
Dr George Ntaios would like to gratefully acknowledge Dr Alireza Minagar, the previous contributor to this
topic. AM declares that he has no competing interests.
// Peer Reviewers:
Julien Morier, MD
Neurology Registrar
Neurology Service, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
DISCLOSURES: JM declares that he has no competing interests.
Louis R. Caplan, MD
Lecturer in Neurology
Hospital Chief, Cerebrovascular/Stroke Division, Beth Israel Deaconess Medical Center, Division of
Cerebrovascular/Stroke, Boston, MA
DISCLOSURES: LRC declares that he has no competing interests.
Tony Rudd, MD
National Clinical Director
Stroke NHS England, Professor, Stroke Medicine, Kings College London, Chair, Intercollegiate Stroke
Working Party, Royal College of Physicians, London, UK
DISCLOSURES: TR declares that he has no competing interests.
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