ESO Stroke Guideline 2008

Guidelines for Management of
Ischaemic Stroke 2008
The European Stroke Organization

- ESO -
Executive Committee and
Writing Committee
MISSION OF ESO
To reduce the incidence and burden

of stroke by changing the way
stroke is viewed and treated in Europe
Guidelines Ischaemic Stroke 2008

ESO Guidelines 2008
• Content:
– Education, Referral and Emergency room
– Stroke Unit
– Imaging and Diagnostics
– Prevention
– General Treatment
– Acute Treatment
– Management of Complications
– Rehabilitation
ESO Writing Committee
• Chair:
– Werner Hacke, Heidelberg, Germany
• Co-Chairs:
– Marie-Germaine Bousser, Paris, France
– Gary Ford, Newcastle, UK

• Education, Referral and Emergency room
– Co-Chairs: Michael Brainin, Krems, Austria; José Ferro,
Lisbon, Portugal
– Members: Charlotte Cordonnier, Lille, France; Heinrich
P. Mattle, Bern, Switzerland; Keith Muir, Glasgow, UK;
Peter D. Schellinger, Erlangen, Germany
• Stroke Units
– Co-Chairs: Hans-Christoph Diener, Essen, Germany;
Peter Langhorne, Glasgow, UK
– Members: Antony Davalos, Barcelona, Spain; Gary Ford,
Newcastle, UK; Veronika Skvortsova, Moscow, Russia

• Imaging and Diagnostics
– Co-Chairs: Michael Hennerici, Mannheim, Germany;
Markku Kaste, Helsinki, Finland
– Members: Hugh S. Markus, London, UK; E. Bernd
Ringelstein, Münster, Germany; Rüdiger von Kummer,
Dresden, Germany; Joanna Wardlaw, Edinburgh, UK
• Prevention
– Co-Chairs: Phil Bath, Nottingham, UK; Didier Leys, Lille,
France
– Members: Álvaro Cervera, Barcelona, Spain; László
Csiba, Debrecen, Hungary; Jan Lodder, Maastricht, The
Netherlands; Nils Gunnar Wahlgren, Stockholm
• General Treatment
– Co-Chairs: Christoph Diener, Essen, Germany; Peter
Langhorne, Glasgow, UK
– Members: Antony Davalos, Barcelona, Spain; Gary Ford,
Newcastle, UK; Veronika Skvortsova, Moscow, Russia
• Acute Treatment and Treatment of Complications
– Co-Chairs: Angel Chamorro, Barcelona, Spain;
Bo Norrving, Lund, Sweden
– Members: Valerica Caso, Perugia, Italy; Jean-Louis Mas,
Paris, France; Victor Obach, Barcelona, Spain; Peter A.
Ringleb, Heidelberg, Germany; Lars Thomassen,
Bergen, Norway
• Rehabilitation
– Co-Chairs: Kennedy Lees, Glasgow, UK; Danilo Toni,
Rome, Italy
– Members: Stefano Paolucci, Rome, Italy; Juhani
Sivenius, Kuopio, Finland; Katharina Stibrant
Sunnerhagen, Göteborg, Sweden; Marion F. Walker,
Nottingham, UK; Substantial assistance: Yvonne
Teuschl, Isabel Henriques, Terence Quinn

Definitions of Levels of Evidence
Level A Established as useful/predictive or not useful/predictive for a
diagnostic measure or established as effective, ineffective or harmful
for a therapeutic intervention; requires at least one convincing Class I
study or at least two consistent, convincing Class II studies.
Level B Established as useful/predictive or not useful/predictive for a
for a therapeutic intervention; requires at least one convincing Class II
study or overwhelming Class III evidence.
Level C Established as useful/predictive or not useful/predictive for a
for a therapeutic intervention; requires at least two Class III studies.
Good Recommended best practice based on the experience of the guideline
Clinical development group. Usually based on Class IV evidence indicating
Practice large clinical uncertainty, such GCP points can be useful for health
(GCP) workers.

Classification of Evidence
Evidence classification scheme for a therapeutic intervention
Class I An adequately powered, prospective, randomized, controlled clinical
trial with masked outcome assessment in a representative population
or an adequately powered systematic review of prospective
randomized controlled clinical trials with masked outcome assessment
in representative populations.
Class II Prospective matched-group cohort study in a representative
population with masked outcome assessment or a randomized,
controlled trial in a representative population that lacks one criterion
for class I evidence.
Class III All other controlled trials (including well-defined natural history
controls or patients serving as own controls) in a representative
population, where outcome assessment is independent of patient
treatment.
Class IV Evidence from uncontrolled studies, case series, case reports, or
expert opinion.
Classification of Evidence
Evidence classification scheme for a diagnostic measure
Class I A prospective study in a broad spectrum of persons with the
suspected condition, using a ‘gold standard’ for case definition, where
the test is applied in a blinded evaluation, and enabling the
assessment of appropriate tests of diagnostic accuracy.
Class II A prospective study of a narrow spectrum of persons with the
suspected condition, or a well-designed retrospective study of a broad
spectrum of persons with an established condition (by ‘gold standard’)
compared to a broad spectrum of controls, where test is applied in a
blinded evaluation, and enabling the assessment of appropriate tests
of diagnostic accuracy.
Class III Evidence provided by a retrospective study where either persons with
the established condition or controls are of a narrow spectrum, and
where test is applied in a blinded evaluation.
Class IV Evidence from uncontrolled studies, case series, case reports, or
expert opinion.
ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
Stroke as an Emergency
Education, Referral, Emergency management
• Background
– Stroke is the most important cause of morbidity and
long term disability in Europe1
– Demographic changes are likely to result in an
increase in both incidence and prevalence
– Stroke is also the second most common cause of
dementia, the most frequent cause of epilepsy in the
elderly, and a frequent cause of depression2,3
1: Lopez AD et al. Lancet (2006) 367:1747-1757

2: Rothwell PM et al. Lancet (2005) 366:1773-1783
3: O'Brien JT et al. Lancet Neurol (2003) 2:89-98 Guidelines Ischaemic Stroke 2008
• Background
– Stroke is a medical and occasionally a surgical
emergency
– The majority of ischaemic stroke patients do not reach
the hospital quickly enough
– The delay between stroke onset and hospital
admission is;
• reduced if the Emergency Medical Systems (EMS)
are used
• increased if doctors outside the hospital are
consulted first
• Emergency care in acute stroke depends on a

four-step chain:
– Rapid recognition of, and reaction to, stroke signs and
symptoms
– Immediate EMS contact and priority EMS dispatch
– Priority transport with notification of the receiving
hospital
– Immediate emergency room triage, clinical, laboratory
and imaging evaluation, accurate diagnosis, and
administration of appropriate treatments at the
receiving hospital.
• Delays during acute stroke management have

been identified at three different levels1
– at the population level, due to failure to recognize the
symptoms of stroke and contact emergency services
– at the level of the emergency services and emergency
physicians, due to a failure to prioritize transport of
stroke patients
– at the hospital level, due to delays in neuroimaging
and inefficient in-hospital care
1:Kwan J et al. Age Ageing (2004) 33:116-121 Guidelines Ischaemic Stroke 2008
Education
Recommendations
 Educational programmes to increase awareness of stroke
at the population level are recommended (Class II,
Level B)
 Educational programmes to increase stroke awareness
among professionals (paramedics, emergency
physicians) are recommended (Class II, Level B)

Referral
Recommendations (1/2)
 Immediate EMS contact and priority EMS dispatch are
recommended (Class II, Level B)
 Priority transport with advance notification of the receiving
hospital is recommended (Class III, Level B)
 Suspected stroke victims should be transported without
delay to the nearest medical centre with a stroke unit that
can provide ultra-early treatment (Class III, Level B)
 Patients with suspected TIA should be referred without
delay to a TIA clinic or a stroke unit (Class III, Level B)

Referral
 Dispatchers and ambulance personnel should be trained
to recognise stroke using simple instruments such as the
Face-Arm-Speech-Test (Class IV, GCP)
 Immediate emergency room triage, clinical, laboratory
and imaging evaluation, accurate diagnosis, therapeutic
decision and administration of appropriate treatments are
recommended (Class III, Level B)
 In remote or rural areas helicopter transfer and
telemedicine should be considered to improve access to
treatment (Class III, Level C)
Emergency Management
• The time window for treatment of patients with

acute stroke is narrow
– Acute emergency management of stroke requires
parallel processes operating at different levels of
patient management
– Acute assessment of neurological and vital functions
parallels the treatment of acutely life-threatening
conditions
• Time is the most important factor

• The initial examination should include

– Observation of breathing and pulmonary function and
concomitant heart disease
– Assessment of blood pressure and heart rate
– Determination of arterial oxygen saturation
– Blood samples for clinical chemistry, coagulation and
haematology studies
– Observation of early signs of dysphagia
– Targeted neurological examination
– Careful medical history focussing on risk factors for
arteriosclerosis and cardiac disease
Ancillary Diagnostic Tests
• In all patients
– Brain Imaging: CT or MRI
– ECG
Diagnostics
– Laboratory Tests
• Complete blood count and platelet count,
prothrombin time or INR, PTT
• Serum electrolytes, blood glucose
• CRP or sedimentation rate
• Hepatic and renal chemical analysis

Ancillary Diagnostic Tests
• In selected patients
– Duplex / Doppler ultrasound
– MRA or CTA
Diagnostics
– Diffusion and perfusion MR or perfusion CT

– Echocardiography, Chest X-ray
– Pulse oximetry and arterial blood gas analysis
– Lumbar puncture
– EEG
– Toxicology screen

Recommendations
 Organization of pre-hospital and in-hospital pathways and
systems for acute stroke patients is recommended (Class
III, Level C)
 All patients should receive brain imaging, ECG, and
laboratory tests. Additional diagnostic examinations are
necessary in selected patients (Class IV, GCP)

ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
Stroke Unit
• A stroke unit
– Is a dedicated and geographically defined part of a
hospital that takes care of stroke patients
– Has specialised staff with coordinated multidisciplinary
expert approach to treatment and care
– Comprises core disciplines: medical, nursing,
physiotherapy, occupational therapy, speech and
language therapy, social work 1
1:Langhorne P et al. Age Ageing (2002) 31:365-371 Guidelines Ischaemic Stroke 2008
Stroke Unit
• Typical components of stroke units include

– Assessment
• Medical assessment and diagnosis, early
assessment of nursing and therapy needs
– Early management policies
• Early mobilisation, prevention of complications,
treatment of hypoxia, hyperglycaemia, pyrexia and
dehydration
– Ongoing rehabilitation policies
• Coordinated multidisciplinary team care
• Early assessments of needs after discharge
Stroke Unit
• Treatment at a stroke unit compared to treatment

in a general ward1
– reduces mortality (absolute risk reduction of 3%)
– reduces dependency (5%)
– reduces need for institutional care (2%)
• All types of patients, irrespective of gender, age,

stroke subtype and stroke severity, appear to
benefit from treatment in stroke units1
1:Stroke Unit Trialists' Collaboration Cochrane Rev (2007) Guidelines Ischaemic Stroke 2008
Stroke Services and Stroke Units
Recommendations
 All stroke patients should be treated in a stroke unit
(Class I, Level A)
 Healthcare systems must ensure that acute stroke
patients can access high technology medical and surgical
stroke care when required (Class III, Level B)
 The development of clinical networks, including
telemedicine, is recommended to expand the access to
high technology specialist stroke care (Class II, Level B)

ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
Emergency Diagnostic Tests
• Differentiate between different types of stroke

– Assess the underlying cause of brain ischaemia
– Assess prognosis
Diagnostics
• Provide a basis for physiological monitoring of

the stroke patient
• Identify concurrent diseases or complications
associated with stroke
• Rule out other brain diseases

• Cranial Computed Tomography (CT)

– Immediate plain CT scanning distinguishes reliably
between haemorrhagic and ischaemic stroke
Diagnostics
– Detects signs of ischaemia as early as 2 h after stroke

onset1
– Helps to identify other neurological diseases (e.g.
neoplasms)
– Most cost-effective strategy for imaging acute stroke
patients2
1: von Kummer R et al. Radiology (2001) 219:95-100

2: Wardlaw J et al. Stroke (2004) 35:2477-2483 Guidelines Ischaemic Stroke 2008
• Magnetic Resonance Imaging (MRI)

– Diffusion-weighted MRI (DWI) is more sensitive for
detection of early ischaemic changes than CT
Diagnostics
– DWI can be negative in patients with definite stroke1

– Identifies ischaemic lesions in the posterior fossa
reliably
– Detects even small intracerebral haemorrhages
reliably on T2* sequences
– MRI is particularly important in acute stroke patients
with unusual presentations
1: Ay H et al. Cerebrovasc Dis (2002) 14:177-186 Guidelines Ischaemic Stroke 2008

• Mismatch Concept
– Mismatch between tissue abnormal on DWI and tissue
with reduced perfusion may reflect tissue at risk of
Diagnostics
further ischaemic damage1

– There is disagreement on how to best identify
irreversible ischaemic brain injury and to define
critically impaired blood flow2
– There is no clear evidence that patients with particular
perfusion patterns are more or less likely to benefit
from thrombolysis3
1: Jansen O et al. Lancet (1999) 353:2036-2037
2: Kane I et al. Stroke (2007) 38:3158-3164
3: Albers GW et al. Ann Neurol (2006) 60:508-517 Guidelines Ischaemic Stroke 2008
• Ultrasound studies
– Cerebrovascular ultrasound is fast and non-invasive
and can be administered using portable machines.
Diagnostics
– It is therefore applicable to patients unable to co-

operate with MRA or CTA1
– Combinations of ultrasound imaging techniques and
MRA can produce excellent results that are equal to
Digital subtraction angiography (DSA)2
1: Allendörfer J et al. Lancet Neurology (2005) 5:835-840

2: Nederkoorn P et al. Stroke (2003) 34:1324-1332 Guidelines Ischaemic Stroke 2008
• Imaging in TIA-patients
– Up to 10% recurrence risk in the first 48 hours1
– Simple clinical scoring systems can be used to identify
Diagnostics
patients at particularly high risk1

– Up to 50% of patients with TIAs have acute ischaemic
lesions on DWI. These patients are at increased risk of
early recurrent disabling stroke2
– There is currently no evidence that DWI provides
better stroke prediction than clinical risk scores3
1: Rothwell P et al. Lancet Neurol (2005) 5:323-331

2: Coutts S et al. Ann Neurol (2005) 57:848-854
3: Redgrave J et al. Stroke (2007) 38:1482-1488 Guidelines Ischaemic Stroke 2008
• Electrocardiogram (ECG)
– Cardiac abnormalities are common in acute stroke
patients1
Diagnostics
– Arrhythmias may induce stroke, stroke may cause

arrhythmias
– Holter monitoring is superior to routine ECG for the
detection of atrial fibrillation (AF)2
– It is unclear whether continuous ECG recording at the
bedside is equivalent to Holter monitoring for the
detection of AF
1: Christensen H et al. Neurol Sci (2005) 234:99 –103
2: Gunalp M et al. Adv Ther (2006) 23:854-60 Guidelines Ischaemic Stroke 2008
• Echocardiography (TTE / TOE)

– Echocardiography can detect many potential causes of
stroke1
Diagnostics
– It is particularly required in patients with history of

cardiac disease, ECG pathologies, suspected source
of embolism, suspected aortic disease, suspected
paradoxical embolism
– Transoesophageal echocardiography (TOE) might be
superior to transthoracic echocardiography (TTE) for
the detection of potential cardiac sources of embolism2
1: Lerakis S et al. Am J Med Sci (2005) 329:310-6

2: de Bruijn SF et al. Stroke (2006) 37:2531-4 Guidelines Ischaemic Stroke 2008
• Laboratory tests
– Haematology (RBC, WBC, platelet count)
– Basic clotting parameters
Diagnostics
– Electrolytes
– Renal and hepatic chemistry
– Blood Glucose
– CRP, sedimentation rate

Diagnostic Imaging
Recommendations
 In patients with suspected TIA or stroke, urgent cranial CT
(Class I), or alternatively MRI (Class II), is recommended
(Level A)
 If MRI is used, the inclusion of diffusion weighted imaging
(DWI) and T2*-weighted gradient echo sequences is
recommended (Class II, Level A)
 In patients with TIA, minor stroke, or early spontaneous
recovery immediate diagnostic work-up, including urgent
vascular imaging (ultrasound, CT-angiography, or MR
angiography) is recommended (Class I, Level A)
Other Diagnostics
 In patients with acute stroke and TIA, early evaluation of
physiological parameters, routine blood tests, and
Diagnostics
electrocardiography (ECG) is recommended (Class I,

Level A)
 All acute stroke and TIA patients should have a 12-
channel ECG. Continuous ECG recording is
recommended for ischaemic stroke and TIA patients
(Class I, Level A)

Other Diagnostics
 For stroke and TIA patients seen after the acute phase,
24-hour Holter ECG monitoring should be performed
Diagnostics
when arrhythmias are suspected and no other causes of

stroke are found (Class I, Level A)
 For all stroke and TIA patients, a sequence of blood tests
is recommended
 Echocardiography is recommended in selected patients
(Class III, Level B)

ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
Primary Prevention
• Content
– Management of vascular risk factors
Primary Prevention
– Antithrombotic therapy
– Carotid surgery and angioplasty

Vascular Risk Factors
• Conditions and lifestyle characteristics identified

as a risk factors for stroke
Primary Prevention
High blood pressure High Cholesterol

Atrial fibrillation Hyper-homocysteinaemia
Diabetes mellitus Smoking
Carotid artery disease Heavy alcohol use
Myocardial infarction Physical inactivity
Obesity

High blood pressure (BP)
• Background
– High blood pressure (>120/80mmHg) is the most
Primary Prevention
important and prevalent modifiable risk factor for

stroke
– Significant reduction of stroke incidence with a
decrease in BP1
– No class of antihypertensive is clearly superior
• LIFE: lorsatan is superior to atenolol2
• ALLHAT: chlorthalidone is more effective than amlodipine and
lisinopril3
1: Neal B et al. Lancet (2000) 356:1955-64

2: Dahlof B et al. Lancet (2002) 359:995-1003.
3: Mancia G et al. Eur Heart J (2007) 28:1462-536 Guidelines Ischaemic Stroke 2008
Diabetes mellitus
• Background
– Independent risk factor for ischaemic stroke
Primary Prevention
– Improving glucose control may not reduce stroke1

– BP in patients with diabetes should be <130/80mmHg2
– Statin treatment reduces the risk of major vascular
events, including stroke3
– Elevated blood glucose in the early phase of stroke is
associated with death and poor recovery
1: Turner RC et al. JAMA (1999) 281:2005-12

2: Mancia GJ: Hypertens Suppl (2007) 25:S7-12
3: Sever PS et al. Diabetes Care (2005) 28:1151-7 Guidelines Ischaemic Stroke 2008
High Cholesterol
• Background
– Statin treatment reduces the incidence of stroke from
Primary Prevention
3.4% to 2.7%1
– No significant effect for prevention of fatal stroke1
– Heart Protection Study found an excess of myopathy
of one per 10,000 patients per annum2
– No data support statin treatment in patients with LDL-
cholesterol <150 mg/dl (3.9 mmol/l)
1: Amarenco P et al.: Stroke (2004) 35:2902-2909

2: HPS Group: Lancet (2002) 360:7-22. Guidelines Ischaemic Stroke 2008
Cigarette Smoking
• Background
– Independent risk factor for ischaemic stroke in men
Primary Prevention
and women
– 2-3 fold increased risk compared to non-smokers1
– Spousal cigarette smoking may be associated with an
increased stroke risk2
– 50% risk reduction by 2 years after stopping smoking3
1: Shinton R et al.: BMJ (1989) 298:789-94.

2: Qureshi A et al.: Stroke (2005) 36:74-76
3: Colditz GA et al.: N Engl J Med (1988) 318:937-41. Guidelines Ischaemic Stroke 2008
Alcohol Consumption
• Background
– Increased risk for both ischaemic (RR 1.69) and
Primary Prevention
haemorrhagic stroke (RR 2.18) with heavy alcohol

consumption (>60g/day)1
– BP elevation might be a reasonable explanation3
– Light alcohol consumption (<12g/day) associated with
reduced ischaemic (RR 0.80) and haemorrhagic
stroke1
– Red wine consumption carries the lowest risk2
1: Reynolds K et al.: JAMA (2003) 289:579-88

2: Mukamal K et al.: Ann Intern Med (2005) 142:11-19
3: Bazzano LA et al.: Ann Neurol (2007) Guidelines Ischaemic Stroke 2008
Physical Activity
• Background
– Regular exercise (at least 3x30min/week) is
Primary Prevention
associated with a decreased risk of stroke

– Physically active individuals have a lower risk of stroke
or death than those with low activity (RR 0.73)1
– This is mediated, in part, through beneficial effects on
body weight, blood pressure, serum cholesterol, and
glucose tolerance2
1: Lee C et al.: Stroke (2003) 34:2475-2481

2: Deplanque D et al.: Neurology (2006) 67:1403-1410) Guidelines Ischaemic Stroke 2008
Body Weight, Diet, Nutrition
• Background
– High body mass index (BMI ≥25) increases risk of
Primary Prevention
stroke in men and women1

– Abdominal adiposity is a risk factor for stroke in men
but not women2
– A randomized trial in women found no effect of dietary
interventions to reduce the incidence of stroke3
– Tocopherol and beta carotene supplementation do not
reduce the risk of stroke. Vitamin E might increase
mortality when used at high-dose (≥400 IU/d)
1: Kurth T et al.: Circulation (2005) 111:1992-1998
2: Hu G et al.: Arch Intern Med (2007) 167:1420-1427
3: Howard B et al.: JAMA (2006) 295:655-666 Guidelines Ischaemic Stroke 2008
Hormone Replacement Therapy
• Background
– Stroke rates rise rapidly in women after the
Primary Prevention
menopause
– Hormone replacement therapy in postmenopausal
women is associated with an 44% increased risk of
stroke1
1: Gabriel S et al.: Cochrane Review (2005) CD002229 Guidelines Ischaemic Stroke 2008
Risk Factor Management
 Blood pressure should be checked regularly. High blood
Primary Prevention
pressure should be managed with lifestyle modification

and individualized pharmacological therapy (Class I,
Level A) aiming at normal levels of 120/80 mmHg (Class
IV, GCP)

 Blood glucose should be checked regularly. Diabetes
Primary Prevention
should be managed with lifestyle modification and

individualized pharmacological therapy (Class IV, Level
C).
 In diabetic patients, high blood pressure should be
managed intensively (Class I, Level A) aiming for levels
below 130/80 mmHg (Class IV, Level C). Where
possible, treatment should include an angiotensin
converting enzyme inhibitor or angiotensin receptor
antagonist (Class I, Level A)
 Blood cholesterol should be checked regularly. High blood
Primary Prevention
cholesterol (e.g. LDL>150mg/dl [3,9mMol/l]) should be

managed with lifestyle modification (Class IV, Level C)
and a statin (Class I, Level A)
 Cigarette smoking should be discouraged (Class III,
Level B)
 Heavy use of alcohol should be discouraged (Class III,
Level B)
 Regular physical activity is recommended (Class III,
Level B)
 A diet low in salt and saturated fat, high in fruit and
Primary Prevention
vegetables and rich in fibre is recommended (Class III,

Level B)
 Subjects with an elevated body mass index are
recommended to take a weight-reducing diet (Class III,
Level B)
 Antioxidant vitamin supplements are not recommended
(Class I, Level A)
 Hormone replacement therapy is not recommended for
the primary prevention of stroke (Class I, Level A)
Antithrombotic Therapy
• Background
– In low risk persons low dose aspirin reduced coronary
Primary Prevention
events, but not stroke1

– In women over 45 years aspirin reduces the risk of
ischaemic stroke (OR 0.76; 95%CI 0.63-0.93) 2
– Aspirin reduces MI in patients with asymptomatic
carotid artery disease3
1: Bartolucci A et al.: Am J Cardiol (2006) 98:746-750

2: Berger J et al.: JAMA (2006) 295:306-313
3: Hobson R, 2nd et al.: J Vasc Surg (1993) 17:257-263 Guidelines Ischaemic Stroke 2008
Atrial fibrillation (AF)
• Background
– Average stroke rate of 5% per year
Primary Prevention
– Aspirin reduces stroke (RR 0.78) in patients with non-

valvular AF1
– Warfarin (INR 2.0-3.0) is more effective than aspirin at
reducing stroke (RR 0.36; 95%CI 0.26-0.51)1
– Combination of aspirin and clopidogrel is less effective
than warfarin and has a similar bleeding rate2
1: Hart RG et al.: Ann Intern Med (2007) 146:857-867

2: Connolly S et al.: Lancet (2006) 367:1903-1912 Guidelines Ischaemic Stroke 2008
Atrial fibrillation (AF)
• Background
– Anticoagulation with an INR below 2.0 is not effective
Primary Prevention
– Increased risk for bleeding complications with an INR

> 3.5
– Patients <65 years of age with “lone AF” (without other
risk factors) are at low risk, whereas patients older
than 65 years are at a higher risk for embolic stroke
– Anticoagulation can be safe and effective in older
individuals1, 2
1: Rash A et al.: Age Ageing (2007) 36:151-156

2: Mant J et al.: Lancet (2007) 370:493-503 Guidelines Ischaemic Stroke 2008
 Low-dose aspirin is recommended in women aged 45
Primary Prevention
years or more who are not at increased risk for

intracerebral haemorrhage and who have good gastro-
intestinal tolerance; however, its effect is very small
(Class I, Level A)
 Low-dose aspirin may be considered in men for the
primary prevention of myocardial infarction; however, it
does not reduce the risk of ischaemic stroke (Class I,
Level A)

 Antiplatelet agents other than aspirin are not
Primary Prevention
recommended for primary stroke prevention (Class IV,

GCP)
 Aspirin may be recommended for patients with non-
valvular AF who are younger than 65 years and free of
vascular risk factors (Class I, Level A)
 Unless contraindicated, either aspirin or an oral
anticoagulant (international normalized ratio [INR] 2.0-
3.0) is recommended for patients with non-valvular AF
who are aged 65-75 years and free of vascular risk
factors (Class I, Level A) Guidelines Ischaemic Stroke 2008
 Unless contraindicated, an oral anticoagulant (INR 2.0–
Primary Prevention
3.0) is recommended for patients with non-valvular AF

who are aged >75, or who are younger but have risk
factors such as high blood pressure, left ventricular
dysfunction, or diabetes mellitus (Class I, Level A)

 Patients with AF who are unable to receive oral
Primary Prevention
anticoagulants should be offered aspirin (Class I, Level

A)
 Patients with AF who have mechanical prosthetic heart
valves should receive long-term anticoagulation with a
target INR based on the prosthesis type, but not less than
INR 2–3 (Class II, Level B)
 Low dose aspirin is recommended for patients with
asymptomatic internal carotid artery (ICA) stenosis >50%
to reduce their risk of vascular events (Class II, Level B)
Asymptomatic carotid artery
(ICA) stenosis
• Background1,2
– Carotid endarterectomy (CEA) is still a matter of
Primary Prevention
controversy in asymptomatic individuals

• RRR for stenosis >60%NASCET is 38-53%
• ARR is 5.9-12.6%
• NNT to avoid one stroke/year is 63-166
– The combined surgical risk must not exceed 3%
1: ACAS: JAMA (1995) 273:1421-8.

2: ACST: Lancet (2004) 363:1491-1502 Guidelines Ischaemic Stroke 2008
Asymptomatic carotid artery
(ICA) stenosis
• Specific issues
– No prospective trials tested the benefit of antiplatelet
Primary Prevention
drugs in patients with asymptomatic carotid stenosis1

– The ipsilateral stroke risk increases with the degree of
the stenosis2
– Patients with an occlusion of the contralateral ICA do
not benefit from endarterectomy3
– Women have lower benefit from CEA than men3
– Aspirin reduces stroke risk during and after CEA4
1: Chambers BR et al.: Cochrane Review (2005)
2: ECST Group: Lancet (1995) 345:209-12
3: Baker WH et al.: Stroke (2000) 31:2330-4
4: Engelter S et al.: Cochrane Reviews (2003) Guidelines Ischaemic Stroke 2008
Carotid Surgery and Angioplasty
Recommendations
 Carotid surgery is not recommended for asymptomatic
Primary Prevention
individuals with significant carotid stenosis (NASCET 60-

99%), except in those at high risk of stroke (Class I,
Level C)
 Carotid angioplasty, with or without stenting, is not
recommended for patients with asymptomatic carotid
stenosis (Class IV, GCP)
 Patients should take aspirin before and after CEA (Class
I, Level A)

Secondary Prevention
• Content
– Management of vascular risk factors
– Antithrombotic therapy
– Surgery and angioplasty

Blood pressure control
• Background
– Antihypertensive drugs reduce stroke recurrence risk
after stroke or TIA (RR 0.76; 95%CI 0.63-0.92)1

– Target BP level and reduction should be individualized
– The reduction in stroke occurs regardless of baseline
BP and type of stroke2
1: Rashid P et al.: Stroke (2003) 34:2741-8

2: PROGRESS group: Lancet (2001) 358:1033-41
Diabetes mellitus
• Background
– In people with type 2 diabetes with previous stroke
pioglitazone reduces fatal or nonfatal stroke (HR 0.53;

95%CI 0.34-0.85; P=0.0085)1
– In addition there is a trend to reduce the combined end
point of death and major vascular events (HR 0.78;
95%CI 0.60-1.02; P=0.067)1
1: Wilcox R et al.: Stroke (2007) 38:865-73 Guidelines Ischaemic Stroke 2008

High Cholesterol
• Background
– Atorvastatin (80mg) reduces stroke recurrence by
16%1
– Simvastatin (40mg) reduces risk of vascular events in
patients with prior stroke, and of stroke in patients with
other vascular disease (RR 0.76)2
– ARR for statin treatment is low (NNT 112-143 for 1
year)1
– Statin withdrawal at the acute stage of stroke may be
harmful3
1: Amarenco P et al.: N Engl J Med (2006) 355:549-559
2: Heart Protection Study: Lancet (2002) 360:7-22
3: Blanco M et al.: Neurology (2007) 69:904-10 Guidelines Ischaemic Stroke 2008
Vitamins
• Background
– Beta carotene increased the risk (RR 1.10) of
cardiovascular death1
– Antioxidant supplements may increase mortality2
– Folate, B12, B6 vitamins given to lower homocysteine
levels may not reduce stroke recurrence and may
increase vascular events3
1: Vivekananthan D et al.: Lancet (2003) 361:2017-2023

2: Bjelakovic G et al.: JAMA (2007) 297:842-857
3: Bonaa K et al.: N Engl J Med (2006) 354:1578-1588 Guidelines Ischaemic Stroke 2008
Hormone Replacement Therapy
• Background
– Oestrogen therapy is not effective in secondary
prevention after TIA or stroke and may increase stroke

severity1
1: Viscoli CM et al.: N Engl J Med (2001) 345:1243-9. Guidelines Ischaemic Stroke 2008
Sleep-disordered Breathing
• Background
– Sleep-disordered breathing (SDB) is both a risk factor
and a consequence of stroke

– More than 50% of stroke patients have SDB, mostly in
the form of obstructive sleep apnoea (OSA).
– SDB is linked with poorer long-term outcome and
increased long-term stroke mortality1
– Continuous positive airway pressure is the treatment of
choice for OSA.
1: Bassetti CL: Semin Neurol (2005) 25:19-32 Guidelines Ischaemic Stroke 2008
 Blood pressure should be checked regularly. Blood
pressure lowering is recommended after the acute phase,

including in patients with normal blood pressure (Class I,
Level A)
 Blood glucose should be checked regularly. Diabetes
should be managed with lifestyle modification and
individualized pharmacological therapy (Class IV, GCP)
 In patients with type 2 diabetes who do not need insulin,
treatment with pioglitazone is recommended after stroke
 Statin therapy is recommended (Class I, Level A)
 Cigarette smoking should be stopped (Class III, Level C)

 Heavy use of alcohol should be discouraged (Class IV,
GCP)
 Regular physical activity is recommended (Class IV,
GCP)
 A diet low in salt and saturated fat, high in fruit and vege-
tables, and rich in fibre is recommended (Class IV, GCP)

 Subjects with an elevated body mass index are
recommended to take a weight-reducing diet (Class IV,

Level C)
 Antioxidant vitamins supplements are not recommended
(Class I, Level A)
 Hormone replacement therapy is not recommended for
the secondary prevention of stroke (Class I, Level A)
 Sleep-disordered breathing such as obstructive sleep
apnoea is recommended to be treated with continuous
positive airway pressure breathing (Class III, Level GCP)
• Background: Aspirin
– 13% relative risk reduction for stroke after TIA or
stroke1
– Most widely studied dosages of aspirin are 50-150mg
– The incidence of GI-disturbances with aspirin is dose
dependent
– No difference in effectiveness amongst low (< 160mg),
medium (160 – 325mg) or high (500 - 1500mg) dose
aspirin
1: Antithrombotic Trialists' Collaboration: BMJ (2002) 324:71-86 Guidelines Ischaemic Stroke 2008
• Background: Dipyridamole plus aspirin

– Relative risk reduction of vascular death, stroke or
myocardial infarction with the combination is

significantly greater (RR 0.82; 95%CI 0.71-0.91) than
with aspirin alone1,2
– ARR 1.0% per year (NNT 100)2
– Incidence of dipyridamole induced headache may be
reduced by increasing the dose gradually3
1: Diener HC et al.: J Neurol Sci (1996) 143:1-13

2: Halkes P et al.: Lancet (2006) 367:1665-1673
3: Chang YJ et al.: Cerebrovasc Dis (2006) 22:258-62 Guidelines Ischaemic Stroke 2008
• Dipyridamole plus aspirin versus aspirin: Meta-analysis1
– Reduced vascular endpoint (vascular death, stroke,
myocardial infarction) with dipyridamole plus aspirin
1: Halkes P et al.: Lancet (2006) 367:1665-1673 Guidelines Ischaemic Stroke 2008

• Background: Clopidogrel:
– Clopidogrel is slightly but significantly more effective
than medium-dose aspirin (RRR 8.7%, ARR 0,5%) in

preventing vascular events in patients with previous
stroke, MI or PAD1
1: CAPRIE Steering Committee: Lancet (1996) 348:1329-1339 Guidelines Ischaemic Stroke 2008
• Background: Clopidogrel plus aspirin

– Compared with clopidogrel the combination of aspirin
and clopidogrel does not reduce the risk of ischaemic

stroke, myocardial infarction, vascular death, or re-
hospitalisation1
– Compared with aspirin alone the combination does not
reduce the risk of myocardial infarction, stroke, or
cardiovascular death2
– Risk of life-threatening or major bleeding is
increased1,2
1: Diener H et al.: Lancet (2004) 364:331-337

2: Bhatt D et al.: N Engl J Med (2006) 354:1706-1717 Guidelines Ischaemic Stroke 2008
 Patients should receive antithrombotic therapy (Class I,
Level A)
 Patients not requiring anticoagulation should receive
antiplatelet therapy (Class I, Level A). Where possible,
combined aspirin and dipyridamole, or clopidogrel alone,
should be given. Alternatively, aspirin alone, or triflusal
alone, may be used (Class I, Level A)

 The combination of aspirin and clopidogrel is not
recommended in patients with recent ischaemic stroke,

except in patients with specific indications (e.g. unstable
angina or non-Q-wave MI during the last 12 months, or
recent stenting); treatment should be given for up to 9
months after the event (Class I, Level A)
 Patients who have a stroke on antiplatelet therapy should
be re-evaluated for pathophysiology and risk factors
(Class IV, GCP)

Anticoagulation
• Background
– Oral antiocoagulation (target INR 2.0 – 3.0) reduces
the risk of recurrent stroke in patients with AF1

– Oral anticoagulation is well established for other
causes of embolism such as mechanical prosthetic
valve replacement, rheumatic valvular heart disease,
ventricular aneurysm and cardiomyopathy
– There is no indication for oral anticoagulation in
patients with non-cardiac cause of ischaemic stroke2
1: EAFT Study Group: Lancet (1993) 342:1255-1262

2: Mohr JP et al.: N Engl J Med (2001) 345:1444-1451 Guidelines Ischaemic Stroke 2008
Anticoagulation
• Specific issues
– In patients with AF and stable coronary disease,
aspirin should not be added to oral anticoagulation1

– Some retrospective studies suggest that anticoagu-
lation may be beneficial in aortic atheroma2, fusiform
basilar artery aneurysms3, or arterial dissection4
– It is unclear if patients with patent foramen ovale
(PFO) benefit from oral anticoagulation5
1: Flaker GC et al.: Am Heart J (2006) 152:967-73

2: Dressler FA et al.: J Am Coll Cardiol (1998) 31:134-8
3: Echiverri HC et al.: Stroke (1989) 20:1741-7
4: Engelter ST et al.: Stroke (2007) 38:2605-11
5: Mas JL et al.: N Engl J Med (2001) 345:1740-6 Guidelines Ischaemic Stroke 2008
 Anticoagulation should not be used after non-cardio-
embolic ischaemic stroke, except in some specific

situations, such as aortic atheromas, fusiform aneurysms
of the basilar artery, cervical artery dissection, or patent
foramen ovale in the presence of proven deep vein
thrombosis (DVT) or atrial septal aneurysm (Class IV,
GCP)
 If oral anticoagulation is contraindicated, combined low
dose aspirin and dipyridamole should be given (Class IV,
GCP)
 Oral anticoagulation (INR 2.0–3.0) is recommended after
ischaemic stroke associated with AF (Class I, Level A).

Oral anticoagulation is not recommended in patients with
co-morbid conditions such as falls, poor compliance,
uncontrolled epilepsy, or gastrointestinal bleeding (Class
III, Level C). Increasing age alone is not a
contraindication to oral anticoagulation (Class I, Level A)
 Patients with cardioembolic stroke unrelated to AF should
receive anticoagulants (INR 2.0-3.0) if the risk of
recurrence is high (Class III, Level C)
Carotid Endarterectomy (CEA)
• Background1,2
– CEA reduces the risk by 48% of recurrent disabling
stroke or death in patients with 70-99%NASCET ipsilateral

carotid artery stenosis
– If perioperative complications exceed 6%, the benefit
of CEA will diminish; if it approaches 10%, the benefit
will vanish entirely
– There is also some risk reduction in male patients with
50 - 69% stenosis of the ipsilateral carotid artery,
provided that the complication rate is below 3%
1: NASCET Collaborators: NEJM (1991) 325:445-453

2: Warlow C: Lancet (1991) 337:1235-1243 Guidelines Ischaemic Stroke 2008
Carotid Endarterectomy
• Specific issues
– CEA should be performed as soon as possible (ideally
within 2 weeks) after the last cerebrovascular event1,2

– Elderly patients (>75 years) without organ failure or
serious cardiac dysfunction benefit from CEA1
– Women with symptomatic stenosis >70% should
undergo CEA. Women with moderate stenosis should
be treated medically2
1: Rothwell PM et al.: Lancet (2004) 363:915-924

2: Rothwell PM et al.: Stroke (2004) 35:2855-61 Guidelines Ischaemic Stroke 2008
Effect of time from last
symptomatic event to
randomisation on the 5-
year relative risk (RR) of
ipsilateral ischaemic
stroke and any operative
stroke or death with CEA
(pooled data from ECST
and NASCET1)
1: Rothwell PM et al.: Stroke (2004) 35:2855-61 Guidelines Ischaemic Stroke 2008

• Specific issues
– The benefit from CEA is lower with lacunar stroke
– Patients with leuko-araiosis should be made aware of

the increased operative risk
– Occlusion of the contralateral ICA carries a higher
perioperative risk
– Continuation of aspirin is required until surgery, but
heparin may be used in very severe stenosis
– All grading of stenoses should be according to
NASCET-criteria

Carotid Artery Stenting (CAS)
• Background
– No randomized trial has demonstrated equivalent
periprocedural risk for CAS compared to CEA in

treatment of symptomatic carotid artery stenosis
– A European study only marginally failed to prove the
non-inferiority of CAS compared to CEA
– A French study was stopped prematurely because of a
2.5 fold higher risk of any stroke or death after CAS2
1: Ringleb PA et al.: Lancet (2006) 368:1239-1247

2: Mas JL et al.: NEJM (2006) 355:1660-1671 Guidelines Ischaemic Stroke 2008
Carotid Artery Stenting
Metaanalysis CAS vs. CEA
Endpoint: any periprocedural stroke or death
1: Kastrup A et al.: Acta Chir Belg (2007) 107:119-28 Guidelines Ischaemic Stroke 2008
Intracranial Occlusive Disease
• Background
– Extracranial-Intracranial bypass is not beneficial in
preventing stroke in patients with MCA or ICA stenosis

or occlusion1
– No randomized controlled trials have evaluated
angioplasty, stenting, or both for intracranial stenosis
– Several non-randomized trials have shown feasibility
and acceptable safety of intracranial stenting, but the
risk of re-stenosis remains high2,3
1: The EC/IC Bypass Grp: N Engl J Med (1985) 313:1191-200

2: Bose A et al.: Stroke (2007) 38:1531-7
3: SSYLVIA Study investigators: Stroke (2004) 35:1388-92 Guidelines Ischaemic Stroke 2008
Surgery and Angioplasty
 CEA is recommended for patients with 70–99% stenosis
(NASCET criteria) (Class I, Level A). CEA should only be

performed in centres with a perioperative complication
rate (all strokes and death) of less than 6% (Class I,
Level A)
 CEA should be performed as soon as possible after the
last ischaemic event, ideally within 2 weeks (Class II,
Level B)

 CEA may be indicated for certain patients with stenosis of
50–69% (NASCET criteria); males with very recent

hemispheric symptoms are most likely to benefit (Class
III, Level C). CEA for stenosis of 50–69% (NASCET
criteria) should only be performed in centres with a
perioperative complication rate (all stroke and death) of
less than 3% (Class I, Level A)
 CEA is not recommended for patients with stenosis of
less than 50% (NASCET criteria) (Class I, Level A)

 Patients should remain on antiplatelet therapy both before
and after surgery (Class I, Level A)

 Carotid percutaneous transluminal angioplasty and/or
stenting (CAS) is only recommended in selected patients
(Class I, Level A). It should be restricted to the following
subgroups of patients with severe symptomatic carotid
artery stenosis: those with contra-indications to CEA,
stenosis at a surgically inaccessible site, re-stenosis after
earlier CEA, and post-radiation stenosis (Class IV, GCP)

 Patients should receive a combination of clopidogrel and
aspirin immediately before and for at least 1 months after

stenting (Class IV, GCP)
 Endovascular treatment may be considered in patients
with symptomatic intracranial stenosis (Class IV, GPC)

ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
General Stroke Treatment
• Content
– Monitoring
General Treatment
– Pulmonary and airway care

– Fluid balance
– Blood pressure
– Glucose metabolism
– Body temperature

Monitoring
• Continuous monitoring
– Heart rate
General Treatment
– Breathing rate
– O2 saturation
• Discontinuous monitoring
– Blood pressure
– Blood glucose
– Vigilance (GCS), pupils
– Neurological status (e.g. NIH stroke scale or
Scandinavian stroke scale)
Pulmonary function
• Background
– Adequate oxygenation is important
General Treatment
– Improve blood oxygenation by administration of > 2 l

O2
– Risk for aspiration in patients with side positioning
– Hypoventilation may be caused by pathological
respiration pattern
– Risk of airway obstruction (vomiting, oropharyngeal
muscular hypotonia): mechanical airway protection

Blood pressure
• Background
– Elevated in most patients with acute stroke
General Treatment
– BP drops spontaneously during the first days after

stroke
– Blood flow in the critical penumbra passively
dependent on the mean arterial pressure
– There are no adequately sized randomised, controlled
studies guiding BP management

Blood pressure
• Specific issues
– Elevated BP (e.g. up to 200mmHg systolic or
General Treatment
110mmHg diastolic) may be tolerated in the acute

phase of ischaemic stroke without intervention
– BP may be lowered if this is required by cardiac
conditions
– Upper level of systolic BP in patients undergoing
thrombolytic therapy is 180mmHg
– Avoid and treat hypotension
– Avoid drastic reduction in BP

Glucose metabolism
• Background
– High glucose levels in acute stroke may increase the
General Treatment
size of the infarction and reduce functional outcome

– Hypoglycemia can mimic acute ischaemic infarction
– Routine use of glucose potassium insulin (GKI)
infusion regimes in patients with mild to moderate
hyperglycaemia did not improve outcome1
• It is common practise to treat hyperglycemia with insulin
when blood glucose exceeds 180mg/dl2 (10mmol/l)
1: Gray CS et al.: Lancet Neurol (2007) 6:397-406

2: Langhorne P et al.: Age Ageing (2002) 31:365-71. Guidelines Ischaemic Stroke 2008
Body temperature
• Background
– Fever is associated with poorer neurological outcome
General Treatment
after stroke
– Fever increases infarct size in experimental stroke
– Many patients with acute stroke develop a febrile
infection
• There are no adequately sized trials guiding temperature
management after stroke
• It is common practice treat fever (and its cause) when the
temperature reaches 37.5°C

 Intermittent monitoring of neurological status, pulse, blood
General Treatment
pressure, temperature and oxygen saturation is

recommended for 72 hours in patients with significant
persisting neurological deficits (Class IV, GCP)
 Oxygen should be administered if sPO2 falls below 95%
(Class IV, GCP)
 Regular monitoring of fluid balance and electrolytes is
recommended in patients with severe stroke or
swallowing problems (Class IV, GCP)

 Normal saline (0.9%) is recommended for fluid
General Treatment
replacement during the first 24 hours after stroke (Class

IV, GCP)
 Routine blood pressure lowering is not recommended
following acute stroke (Class IV, GCP)
 Cautious blood pressure lowering is recommended in
patients with any of the following; extremely high blood
pressures (>220/120 mmHg) on repeated measurements,
or severe cardiac failure, aortic dissection, or hyper-
tensive encephalopathy (Class IV, GCP)
 Abrupt blood pressure lowering should be avoided (Class
General Treatment
II, Level C)
 Low blood pressure secondary to hypovolaemia or
associated with neurological deterioration in acute stroke
should be treated with volume expanders (Class IV GCP)
 Monitoring serum glucose levels is recommended (Class
IV, GCP)
 Treatment of serum glucose levels >180mg/dl
(>10mmol/l) with insulin titration is recommended (Class
IV, GCP)
 Severe hypoglycaemia (<50 mg/dl [<2.8 mmol/l]) should
General Treatment
be treated with intravenous dextrose or infusion of 10–

20% glucose (Class IV, GCP points)
 The presence of pyrexia (temperature >37.5°C) should
prompt a search for concurrent infection (Class IV, GCP)
 Treatment of pyrexia (>37.5°C) with paracetamol and
fanning is recommended (Class III, Level C)
 Antibiotic prophylaxis is not recommended in
immunocompetent patients (Class II, Level B)

ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
Specific Stroke Treatment
• Content
– Thrombolytic therapy
Specific Treatment
– Early antithrombotic treatment

– Treatment of elevated intracranial pressure
– Prevention and management of complications

Thrombolytic Therapy (i.v. rtPA)
• Background (NINDS1, ECASS I2 + II3, ATLANTIS4)

– Intravenous rtPA (0.9mg/kg, max 90mg) given within 3
Specific Treatment
hours of stroke onset, significantly improves outcome

in patients with acute ischaemic stroke
– Benefit from the use of i.v. rtPA beyond 3 hours is
smaller, but may be present up to at least 4.5 hours
– Several contraindications
1: NINDS rt-PA Grp: New Engl J Med (1995) 333:1581-1587

2: Hacke W et al.: JAMA (1995) 274:1017-1025
3: Hacke W et al.: Lancet (1998) 352:1245-1251
4: Clark WM et al.: Jama (1999) 282:2019-26. Guidelines Ischaemic Stroke 2008
• Specific issues
– A pooled analysis of the 6 i.v. rtPA trials confirms that
Specific Treatment
i.v. thrombolysis may work up to 4.5 hours1

– Caution is advised when considering i.v. rtPA in
persons with severe stroke (NIHSSS>25), or if the CT
demonstrates extended early infarcts signs
– Thrombolytic therapy must be given by an experienced
stroke physician after the imaging of the brain is
assessed by physicians experienced in reading this
imaging study2
1: Hacke W et al.: Lancet (2004) 363:768-74

2: Wahlgren N et al.: Lancet (2007) 369:275-82 Guidelines Ischaemic Stroke 2008
• Specific issues
– Factors associated with increased bleeding risk1
Specific Treatment
• elevated serum glucose

• history of diabetes
• baseline symptom severity
• advanced age
• increased time to treatment
• previous aspirin use
• history of congestive heart failure
• NINDS protocol violations
– None of these reversed the overall benefit of rtPA
1: Lansberg MG et al.: Stroke (2007) 38:2275-8 Guidelines Ischaemic Stroke 2008
Risk and outcome from 6,483 patients of the SITS-Most
treated with iv-rtPA within a 3 hour time window1
Specific Treatment
1: Wahlgren N et al.: Lancet (2007) 369:275-82 Guidelines Ischaemic Stroke 2008

• Mismatch based therapy

– The use of multimodal imaging criteria may be useful
Specific Treatment
for patient selection1,2

– Available data on mismatch, as defined by multimodal
MRI or CT, are too limited to guide thrombolysis in
routine practice3
– Data regarding the use of intravenous desmoteplase
administered 3 to 9 hours after acute ischaemic stroke
in patients selected on the basis of perfusion/diffusion
mismatch are conflicting
1: Köhrmann M et al.: Lancet Neurol (2006) 5:661-7
2: Chalela J et al.: Lancet (2007) 369:293-298
3: Kane I et al.: JNNP (2007) 78:485-490 Guidelines Ischaemic Stroke 2008
Thrombolytic Therapy (i.a.)
• Background: the use of i.a. rtPA, i.a. urokinase

– Only cases and some prospective uncontrolled case
Specific Treatment
series
• Facts: about use of i.a. pro-urokinase

– Efficacy demonstrated in small RCT, 6h window1
– Not approved and substance not available
1: Furlan A et al.: JAMA (1999) 282:2003-11 Guidelines Ischaemic Stroke 2008

Specific Treatment
 Intravenous rtPA (0.9 mg/kg BW, maximum 90 mg), with
Specific Treatment
10% of the dose given as a bolus followed by a 60-minute

infusion, is recommended within 3 hours of onset of
ischaemic stroke (Class I, Level A)
 Intravenous rtPA may be of benefit also for acute
ischaemic stroke beyond 3 hours after onset (Class I,
Level B) but is not recommended for routine clinical
practice. The use of multimodal imaging criteria may be
useful for patient selection (Class III, Level C)

Specific Treatment
 Blood pressures of 185/110 mmHg or higher must be
Specific Treatment
lowered before thrombolysis (Class IV, GCP)

 Intravenous rtPA may be used in patients with seizures at
stroke onset, if the neurological deficit is related to acute
cerebral ischaemia (Class IV, GCP)
 Intravenous rtPA may also be administered in selected
patients over 80 years of age, although this is outside the
current European labelling (Class III, Level C)

Specific Treatment
 Intra-arterial treatment of acute MCA occlusion within a 6-
Specific Treatment
hour time window is recommended as an option (Class II,

Level B)
 Intra-arterial thrombolysis is recommended for acute
basilar occlusion in selected patients (Class III, Level B)
Intravenous thrombolysis for basilar occlusion is an
acceptable alternative even after 3 hours (Class III, Level
B)

Antiplatelet therapy
• Background
– Aspirin was tested in large RCTs in acute (<48 h)
Specific Treatment
stroke1,2
– Significant reduction was seen in death and
dependency (NNT 70) and recurrence of stroke (NNT
140)
– A phase 3 trial for the glycoprotein-IIb-IIIa antagonist
abciximab was stopped prematurely because of an
increased rate of bleeding3
1: International-Stroke-Trial: Lancet (1997) 349:1569-1581

2: CAST-Collaborative-Group: Lancet (1997) 349:1641-1649
3: Adams HP, Jr. et al.: Stroke (2007) Guidelines Ischaemic Stroke 2008
Anticoagulation
• Unfractionated heparin
– No formal trial available testing standard i.v. heparin
Specific Treatment
– IST showed no net benefit for s.c. heparin treated

patients because of increased risk of ICH1
• Low molecular weight heparin
– No benefit on stroke outcome for low molecular
heparin (nadroparin, certoparin, tinzaparin, dalteparin)
• Heparinoid (orgaran)
– TOAST trial neutral2
1: International-Stroke-Trial: Lancet (1997) 349:1569-1581

2: TOAST Investigators: JAMA (1998) 279:1265-72. Guidelines Ischaemic Stroke 2008
Neuroprotection
• No adequately sized trial has yet shown

significant effect in predefined endpoints for any
Specific Treatment
neuroprotective substance
• A meta-analysis has suggested a mild benefit for
citocoline1
1: Davalos A et al.: Stroke (2002) 33:2850-7 Guidelines Ischaemic Stroke 2008

Specific Treatment
 Aspirin (160–325 mg loading dose) should be given within
Specific Treatment
48 hours after ischaemic stroke (Class I, Level A)

 If thrombolytic therapy is planned or given, aspirin or
other antithrombotic therapy should not be initiated within
24 hours (Class IV, GCP)
 The use of other antiplatelet agents (single or combined)
is not recommended in the setting of acute ischaemic
stroke (Class III, Level C)
 The administration of glycoprotein-IIb-IIIa inhibitors is not
recommended (Class I, Level A)
Specific Treatment
 Early administration of unfractionated heparin, low
Specific Treatment
molecular weight heparin or heparinoids is not

recommended for the treatment of patients with
ischaemic stroke (Class I, Level A)
 Currently, there is no recommendation to treat ischaemic
stroke patients with neuroprotective substances (Class I,
Level A)

Elevated Intracranial Pressure
• Basic management
– Head elevation up to 30°
Specific Treatment
– Pain relief and sedation

– Osmotic agents (glycerol, mannitol, hypertonic saline)
– Ventilatory support
– Barbiturates, hyperventilation, or THAM-buffer
– Achieve normothermia
• Hypothermia may reduce mortality1
1: Steiner T et al.: Neurology (2001) 57(Suppl 2):S61-8. Guidelines Ischaemic Stroke 2008
• Malignant MCA/hemispheric infarction

– Pooled analysis of three European RCTs (N=93)1,2:
Specific Treatment
• Significantly decreases mortality after 30 days

• Significantly more patients with mRS <4 or mRS <3
in the decompressive surgery group after one year
• No increase of patients surviving with mRS=5
– Surgery should be done within 48 hours1,2
– Side of infarction did affect outcome1,2
– Age >50 years is a predictor for poor outcome3
1: Vahedi K et al.: Lancet Neurol (2007) 6:215-22
2: Jüttler E et al.: Stroke (2007) 38:2518-25
3: Gupta R et al.: Stroke (2004) 35:539-43 Guidelines Ischaemic Stroke 2008
Absolute risk reduction (ARR) and odds ratio (OR) for unfavourable
outcome at 12 months: combined analysis of decompression trials1
Specific Treatment
1: Vahedi K et al.: Lancet Neurol (2007) 6:215-22 Guidelines Ischaemic Stroke 2008
 Surgical decompressive therapy within 48 hours after
Specific Treatment
symptom onset is recommended in patients up to 60

years of age with evolving malignant MCA infarcts (Class
I, Level A)
 Osmotherapy can be used to treat elevated intracranial
pressure prior to surgery if this is considered (Class III,
Level C)

 No recommendation can be given regarding hypothermic
Specific Treatment
therapy in patients with space-occupying infarctions

(Class IV, GCP)
 Ventriculostomy or surgical decompression can be
considered for treatment of large cerebellar infarctions
that compress the brainstem (Class III, Level C)

ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
Management of Complications
• Aspiration and pneumonia

– Bacterial pneumonia is one of the most important
Specific Treatment
complications in stroke patients1

– Preventive strategies
• Withhold oral feeding until demonstration of intact swallowing,
preferable using a standardized test
• Nasogastric (NG) or percutaneous enteral gastrostomy (PEG)
• Frequent changes of the patient’s position in bed and
pulmonary physical therapy
– Prophylactic administration of levofloxacin is not
superior to optimal care2
1: Weimar C et al.: Eur Neurol (2002) 48:133-40
2: Chamorro A et al.: Stroke (2005) 36:1495-500 Guidelines Ischaemic Stroke 2008
• Urinary tract infections

– Most hospital-acquired urinary tract infections are
Specific Treatment
associated with the use of indwelling catheters1

– Intermittent catheterization does not reduce the risk of
infection
– If urinary infection is diagnosed, appropriate antibiotics
should be chosen following basic medical principles
1: Gerberding JL: Ann Intern Med (2002) 137:665-70c Guidelines Ischaemic Stroke 2008
• Deep vein thrombosis and pulmonary embolism

– Risk might be reduced by good hydration and early
Specific Treatment
mobilization
– Low-dose LMWH reduces the incidence of both DVT
(OR 0.34) and pulmonary embolism (OR 0.36), without
a significantly increased risk of intracerebral (OR 1.39)
or extracerebral haemorrhage (OR 1.44)1,2
1: Diener HC et al.: Stroke (2006) 37:139-44

2: Sherman DG et al.: Lancet (2007) 369:1347-55 Guidelines Ischaemic Stroke 2008
• Pressure ulcer
– Use of support surfaces, frequent repositioning,
Specific Treatment
optimizing nutritional status, and moisturizing sacral

skin are appropriate preventive strategies1
• Seizures
– Prophylactic anticonvulsive treatment is not beneficial
• Agitation
– Causal treatment must precede any type of sedation
or antipsychotic treatment
1: Reddy M et al.: JAMA (2006) 296:974-84 Guidelines Ischaemic Stroke 2008

• Falls
– Are common in every stage of stroke treatment
Specific Treatment
– Risk factors include cognitive impairment, depression,

polypharmacy and sensory impairment1
– A multidisciplinary package focusing on personal and
environmental factors might be preventive2
– Exercise, calcium supplements and bisphosphonates
improve bone strength and decrease fracture rates in
stroke patients3,4
1: Aizen E et al.: Arch Gerontol Geriatr (2007) 44:1-12
2: Oliver D et al.: BMJ (2007) 334:82
3: Pang MY et al.: Clin Rehabil (2006) 20:97-111
4: Sato Y et al.: Cerebrovasc Dis (2005) 20:187-92 Guidelines Ischaemic Stroke 2008
• Dysphagia and feeding

– Dysphagia occurs in up to 50% of patients with
Specific Treatment
unilateral hemiplegic stroke and is an independent

risk-factor for poor outcome1
– For patients with continuing dysphagia, options for
enteral nutrition include NG or PEG feeding
– PEG does not provide better nutritional status or
improved clinical outcome, compared to NG2,3
1: Martino R et al.: Stroke (2005) 36:2756-63

2: Dennis MS et al.: Lancet (2005) 365:764-72
3: Callahan CM et al.: J Am Geriatr Soc (2000) 48:1048-54 Guidelines Ischaemic Stroke 2008
 Infections after stroke should be treated with appropriate
Specific Treatment
antibiotics (Class IV, GCP)

 Prophylactic administration of antibiotics is not
recommended, and levofloxacin can be detrimental in
acute stroke patients (Class II, Level B)
 Early rehydration and graded compression stockings are
recommended to reduce the incidence of venous
thromboembolism (Class IV, GCP)
 Early mobilization is recommended to prevent compli-
cations such as aspiration pneumonia, DVT and pressure
ulcers (Class IV, GCP) Guidelines Ischaemic Stroke 2008
 Low-dose s.c. heparin or low molecular weight heparins
Specific Treatment
should be considered for patients at high risk of DVT or

pulmonary embolism (Class I, Level A)
 Administration of anticonvulsants is recommended to
prevent recurrent seizures (Class I, Level A)
 Prophylactic administration of anticonvulsants to patients
with recent stroke who have not had seizures is not
recommended (Class IV, GCP)
 An assessment of falls risk is recommended for every
stroke patient (Class IV, GCP)
 Calcium/vitamin-D supplements are recommended in
Specific Treatment
stroke patients at risk of falls (Class II, Level B)

 Bisphosphonates (alendronate, etidronate and
risedronate) are recommended in women with previous
fractures (Class II, Level B)
 In stroke patients with urinary incontinence, specialist
assessment and management is recommended (Class
III, Level C)
 Swallowing assessment is recommended but there are
insufficient data to recommend a specific approach for
treatment (Class III, GCP) Guidelines Ischaemic Stroke 2008
 Oral dietary supplements are only recommended for non-
Specific Treatment
dysphagic stroke patients who are malnourished (Class

II, Level B)
 Early commencement of nasogastric (NG) feeding (within
48 hours) is recommended in stroke patients with
impaired swallowing (Class II, Level B)
 Percutaneous enteral gastrostomy (PEG) feeding should
not be considered in stroke patients in the first 2 weeks
(Class II, Level B)

ESO Guidelines 2008
• Content:
– Stroke Unit
– Prevention
– Acute Treatment
– Rehabilitation
Rehabilitation
• Early rehabilitation
– More than 40 % of stroke patients need active
rehabilitation
Rehabilitation
– Active rehabilitation should start early, providing the

patient is clinically stable
– Passive rehabilitation should be given if the patient is
unconscious or paralysed
– Rehabilitation should be continued as long as
perceptable recovery is taking place

Rehabilitation
• Multidisciplinary stroke team for rehabilitation

– Stroke physician
– Nurses experienced in stroke management
Rehabilitation
– Physiotherapist trained in stroke rehabilitation

– Occupational therapist skilled in stroke
– Speech therapist familiar with speech problems in
stroke patients
– Neuropsychologist accustomed to stroke rehabilitation
– Social worker familiar with the problems of stroke
patients
Setting of Rehabilitation
 Admission to a stroke unit is recommended for acute
stroke patients to receive coordinated multidisciplinary
Rehabilitation
rehabilitation (Class I, Level A)

 Early discharge from stroke unit care is possible in
medically stable patients with mild or moderate
impairment providing that rehabilitation is delivered in the
community by a multidisciplinary team with stroke
expertise (Class I, Level A)

Setting of Rehabilitation
 Rehabilitation should be continued after discharge during
the first year after stroke (Class II, Level A)
Rehabilitation
 Early initiation of rehabilitation is recommended (Class III,

Level C)
 It is recommended that the duration and intensity of
rehabilitation is increased (Class II, Level B)

Elements of Rehabilitation
 Physiotherapy is recommended, but the optimal mode of
delivery is unclear (Class I, Level A)
Rehabilitation
 Occupational therapy is recommended, but the optimal

mode of delivery is unclear (Class I, Level A)
 While assessment for communication deficits is
recommended, there are insufficient data to recommend
specific treatments (Class III, GCP)
 Information should be provided to patient and carers but
evidence does not support use of a dedicated stroke
liaison service for all patients (Class II, Level B)
 Rehabilitation must be considered for all stroke patients,
but there is limited evidence to guide appropriate
Rehabilitation
treatment for the most severely disabled (Class II, Level

B)
 While assessment for cognitive deficits appears desirable,
there are insufficient data to recommend specific
treatments (Class I, Level A)
 Patients should be monitored for depression during
hospital stay and throughout follow up (Class IV, Level B)

 Drug therapy and non-drug interventions are
recommended to improve mood (Class I, Level A)
Rehabilitation
 Drug therapy should be considered to treat post stroke

emotionalism (Class II, Level B)
 Tricyclic or anticonvulsant therapy are recommended to
treat post-stroke neuropathic pain in selected patients
 Botulinum toxin should be considered to treat post-stroke
spasticity, but functional benefits are uncertain (Class III,
Level B)

ESO Stroke Guideline 2008

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ESO Stroke Guideline 2008

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Guidelines for Management of

Ischaemic Stroke 2008

The European Stroke Organization

To reduce the incidence and burden

Guidelines Ischaemic Stroke 2008

Guidelines Ischaemic Stroke 2008

Guidelines Ischaemic Stroke 2008

Guidelines Ischaemic Stroke 2008

Guidelines Ischaemic Stroke 2008

1: Lopez AD et al. Lancet (2006) 367:1747-1757

• Emergency care in acute stroke depends on a

• Delays during acute stroke management have

Guidelines Ischaemic Stroke 2008

Guidelines Ischaemic Stroke 2008

• The time window for treatment of patients with

Guidelines Ischaemic Stroke 2008

• The initial examination should include

Guidelines Ischaemic Stroke 2008

– Diffusion and perfusion MR or perfusion CT

Guidelines Ischaemic Stroke 2008

Guidelines Ischaemic Stroke 2008

• Typical components of stroke units include

• Treatment at a stroke unit compared to treatment

• All types of patients, irrespective of gender, age,

Guidelines Ischaemic Stroke 2008

• Differentiate between different types of stroke

• Provide a basis for physiological monitoring of

Guidelines Ischaemic Stroke 2008

• Cranial Computed Tomography (CT)

– Detects signs of ischaemia as early as 2 h after stroke

1: von Kummer R et al. Radiology (2001) 219:95-100

• Magnetic Resonance Imaging (MRI)

– DWI can be negative in patients with definite stroke1

1: Ay H et al. Cerebrovasc Dis (2002) 14:177-186 Guidelines Ischaemic Stroke 2008

further ischaemic damage1

– It is therefore applicable to patients unable to co-

1: Allendörfer J et al. Lancet Neurology (2005) 5:835-840

patients at particularly high risk1

1: Rothwell P et al. Lancet Neurol (2005) 5:323-331

– Arrhythmias may induce stroke, stroke may cause

• Echocardiography (TTE / TOE)

– It is particularly required in patients with history of

1: Lerakis S et al. Am J Med Sci (2005) 329:310-6

Guidelines Ischaemic Stroke 2008

electrocardiography (ECG) is recommended (Class I,

Guidelines Ischaemic Stroke 2008

when arrhythmias are suspected and no other causes of

Guidelines Ischaemic Stroke 2008

Guidelines Ischaemic Stroke 2008

• Conditions and lifestyle characteristics identified

High blood pressure High Cholesterol

Guidelines Ischaemic Stroke 2008

important and prevalent modifiable risk factor for

1: Neal B et al. Lancet (2000) 356:1955-64

– Improving glucose control may not reduce stroke1

1: Turner RC et al. JAMA (1999) 281:2005-12

1: Amarenco P et al.: Stroke (2004) 35:2902-2909

1: Shinton R et al.: BMJ (1989) 298:789-94.

haemorrhagic stroke (RR 2.18) with heavy alcohol

1: Reynolds K et al.: JAMA (2003) 289:579-88

associated with a decreased risk of stroke

1: Lee C et al.: Stroke (2003) 34:2475-2481

stroke in men and women1