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The European Stroke Organization- ESO -

Executive Committee andWriting Committee

Guidelines for Management of

Ischaemic Stroke 2008



Guidelines Ischaemic Stroke 2008

MISSION OF ESO

To reduce the incidence and burdenof stroke by changing the way

stroke is viewed and treated in Europe




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; HeinrichP. 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. BerndRingelstein, 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; LászlóCsiba, Debrecen, Hungary; Jan Lodder, Maastricht, TheNetherlands; Nils Gunnar Wahlgren, Stockholm


http://slidepdf.com/reader/full/eso08-slides-25thapril 7/151Guidelines Ischaemic Stroke 2008


• 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 StibrantSunnerhagen, Göteborg, Sweden; Marion F. Walker,Nottingham, UK; Substantial assistance: YvonneTeuschl, Isabel Henriques, Terence Quinn



Definitions of Levels of Evidence

Level A Established as useful/predictive or not useful/predictive for adiagnostic measure or established as effective, ineffective or harmfulfor a therapeutic intervention; requires at least one convincing Class Istudy or at least two consistent, convincing Class II studies.

Level B Established as useful/predictive or not useful/predictive for a

diagnostic measure or established as effective, ineffective or harmfulfor a therapeutic intervention; requires at least one convincing Class IIstudy or overwhelming Class III evidence.

Level C Established as useful/predictive or not useful/predictive for adiagnostic measure or established as effective, ineffective or harmfulfor a therapeutic intervention; requires at least two Class III studies.

GoodClinicalPractice(GCP)

Recommended best practice based on the experience of the guidelinedevelopment group. Usually based on Class IV evidence indicatinglarge clinical uncertainty, such GCP points can be useful for healthworkers.




Classification of Evidence

Evidence classification scheme for a therapeutic intervention

Class I An adequately powered, prospective, randomized, controlled clinicaltrial with masked outcome assessment in a representative populationor an adequately powered systematic review of prospectiverandomized 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 criterionfor class I evidence.

Class III All other controlled trials (including well-defined natural historycontrols or patients serving as own controls) in a representativepopulation, where outcome assessment is independent of patienttreatment.

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 thesuspected condition, using a „gold standard‟ for case definition, where

the test is applied in a blinded evaluation, and enabling theassessment of appropriate tests of diagnostic accuracy.

Class II A prospective study of a narrow spectrum of persons with thesuspected condition, or a well-designed retrospective study of a broadspectrum of persons with an established condition (by „gold standard‟)

compared to a broad spectrum of controls, where test is applied in ablinded evaluation, and enabling the assessment of appropriate testsof diagnostic accuracy.

Class III Evidence provided by a retrospective study where either persons withthe established condition or controls are of a narrow spectrum, andwhere test is applied in a blinded evaluation.

Class IV Evidence from uncontrolled studies, case series, case reports, or expert opinion.




ESO Guidelines 2008


– Stroke Unit




– Rehabilitation



E d u c a t i o n

, R e f e r r a l , E m e r g e n c y m a n a g e m e n t


Stroke as an Emergency

• Background – Stroke is the most important cause of morbidity and

long term disability in Europe1

– Demographic changes are likely to result in anincrease 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) 366:1773-17833: O'Brien JT et al. Lancet Neurol (2003) 2:89-98



E d u c a t i o n




• Background – Stroke is a medical and occasionally a surgical

emergency

– The majority of ischaemic stroke patients do not reachthe hospital quickly enough

– The delay between stroke onset and hospitaladmission is;

• reduced if the Emergency Medical Systems (EMS)are used

• increased if doctors outside the hospital areconsulted first



E d u c a t i o n




• Emergency care in acute stroke depends on afour-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 receivinghospital

– Immediate emergency room triage, clinical, laboratoryand imaging evaluation, accurate diagnosis, andadministration of appropriate treatments at thereceiving hospital.



E d u c a t i o n

, R e f e r r a l , E m e

r g e n c y m a n a g e m e n t



• Delays during acute stroke management havebeen 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 neuroimagingand inefficient in-hospital care

1:Kwan J et al. Age Ageing (2004) 33:116-121



E d u c a t i o n




Education

Recommendations

Educational programmes to increase awareness of strokeat the population level are recommended (Class II,

Level B) Educational programmes to increase stroke awareness

among professionals (paramedics, emergencyphysicians) are recommended (Class II, Level B)



E d u c a t i o n




Referral

Recommendations (1/2)

Immediate EMS contact and priority EMS dispatch arerecommended (Class II, Level B)

Priority transport with advance notification of the receivinghospital is recommended (Class III, Level B)

Suspected stroke victims should be transported withoutdelay 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)



E d u c a t i o n




Referral


Dispatchers and ambulance personnel should be trainedto recognise stroke using simple instruments such as theFace-Arm-Speech-Test (Class IV, GCP)

Immediate emergency room triage, clinical, laboratoryand imaging evaluation, accurate diagnosis, therapeuticdecision 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 totreatment (Class III, Level C)



E d u c a t i o n




Emergency Management

• The time window for treatment of patients withacute stroke is narrow

– Acute emergency management of stroke requires

parallel processes operating at different levels of patient management

– Acute assessment of neurological and vital functionsparallels the treatment of acutely life-threatening

conditions• Time is the most important factor



E d u c a t i o n





• 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 andhaematology studies

– Observation of early signs of dysphagia

– Targeted neurological examination

– Careful medical history focussing on risk factors for

arteriosclerosis and cardiac disease



D i a g n o s

t i c s


Ancillary Diagnostic Tests

• In all patients – Brain Imaging: CT or MRI

– ECG

– 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



D i a g n o s

t i c s


Ancillary Diagnostic Tests

• In selected patients – Duplex / Doppler ultrasound

– MRA or CTA

– Diffusion and perfusion MR or perfusion CT – Echocardiography, Chest X-ray

– Pulse oximetry and arterial blood gas analysis

– Lumbar puncture

– EEG

– Toxicology screen



E d u c a t i o n ,

R e f e r r a l , E m e




Recommendations

Organization of pre-hospital and in-hospital pathways andsystems for acute stroke patients is recommended (Class

III, Level C)

All patients should receive brain imaging, ECG, andlaboratory tests. Additional diagnostic examinations arenecessary in selected patients (Class IV, GCP)




ESO Guidelines 2008


– Stroke Unit




– Rehabilitation



E d u c a t i o n ,




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 multidisciplinaryexpert 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



E d u c a t i o n ,




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



E d u c a t i o n ,




Stroke Unit

• Treatment at a stroke unit compared to treatmentin 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 tobenefit from treatment in stroke units1

1:Stroke Unit Trialists' Collaboration Cochrane Rev (2007)



E d u c a t i o n ,




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 strokepatients can access high technology medical and surgicalstroke care when required (Class III, Level B)

The development of clinical networks, including

telemedicine, is recommended to expand the access tohigh technology specialist stroke care (Class II, Level B)




ESO Guidelines 2008


– Stroke Unit




– Rehabilitation



D i a g n o s

t i c s


Emergency Diagnostic Tests

• Differentiate between different types of stroke – Assess the underlying cause of brain ischaemia

– Assess prognosis

• Provide a basis for physiological monitoring of the stroke patient

• Identify concurrent diseases or complications

associated with stroke• Rule out other brain diseases



D i a g n o s

t i c s



• Cranial Computed Tomography (CT) – Immediate plain CT scanning distinguishes reliably

between haemorrhagic and ischaemic stroke

– Detects signs of ischaemia as early as 2 h after strokeonset1

– Helps to identify other neurological diseases (e.g.neoplasms)

– Most cost-effective strategy for imaging acute strokepatients2

1: von Kummer R et al. Radiology (2001) 219:95-1002: Wardlaw J et al. Stroke (2004) 35:2477-2483



D i a g n o s

t i c s



• Magnetic Resonance Imaging (MRI) – Diffusion-weighted MRI (DWI) is more sensitive for

detection of early ischaemic changes than CT

– 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



D i a g n o s

t i c s



• Mismatch Concept – Mismatch between tissue abnormal on DWI and tissue

with reduced perfusion may reflect tissue at risk of further ischaemic damage1

– There is disagreement on how to best identifyirreversible ischaemic brain injury and to definecritically impaired blood flow2

– There is no clear evidence that patients with particular perfusion patterns are more or less likely to benefitfrom thrombolysis3

1: Jansen O et al. Lancet (1999) 353:2036-2037

2: Kane I et al. Stroke (2007) 38:3158-31643: Albers GW et al. Ann Neurol (2006) 60:508-517



D i a g n o s

t i c s



• Ultrasound studies – Cerebrovascular ultrasound is fast and non-invasive

and can be administered using portable machines.

– It is therefore applicable to patients unable to co-operate with MRA or CTA1

– Combinations of ultrasound imaging techniques andMRA can produce excellent results that are equal to

Digital subtraction angiography (DSA)2

1: Allendörfer J et al. Lancet Neurology (2005) 5:835-8402: Nederkoorn P et al. Stroke (2003) 34:1324-1332



D i a g n o s

t i c s



• Imaging in TIA-patients – Up to 10% recurrence risk in the first 48 hours1

– Simple clinical scoring systems can be used to identify

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 providesbetter 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) 57:848-8543: Redgrave J et al. Stroke (2007) 38:1482-1488



D i a g n o s

t i c s



• Electrocardiogram (ECG) – Cardiac abnormalities are common in acute stroke

patients1

– Arrhythmias may induce stroke, stroke may causearrhythmias

– Holter monitoring is superior to routine ECG for thedetection of atrial fibrillation (AF)2

– It is unclear whether continuous ECG recording at thebedside is equivalent to Holter monitoring for thedetection of AF

1: Christensen H et al. Neurol Sci (2005) 234:99 –1032: Gunalp M et al. Adv Ther (2006) 23:854-60



D i a g n o s

t i c s



• Echocardiography (TTE / TOE) – Echocardiography can detect many potential causes of

stroke1

– It is particularly required in patients with history of cardiac disease, ECG pathologies, suspected sourceof embolism, suspected aortic disease, suspectedparadoxical embolism

– Transoesophageal echocardiography (TOE) might besuperior to transthoracic echocardiography (TTE) for the detection of potential cardiac sources of embolism2

1: Lerakis S et al. Am J Med Sci (2005) 329:310-62: de Bruijn SF et al. Stroke (2006) 37:2531-4



D i a g n o s

t i c s



• Laboratory tests – Haematology (RBC, WBC, platelet count)

– Basic clotting parameters

– Electrolytes – Renal and hepatic chemistry

– Blood Glucose

– CRP, sedimentation rate



E d u c a t i o n ,


r g e n c y m a n a g e

m e n t


Diagnostic Imaging

Recommendations

In patients with suspected TIA or stroke, urgent cranialCT (Class I), or alternatively MRI (Class II), isrecommended (Level A)

If MRI is used, the inclusion of diffusion weighted imaging(DWI) and T2*-weighted gradient echo sequences isrecommended (Class II, Level A)

In patients with TIA, minor stroke, or early spontaneousrecovery immediate diagnostic work-up, including urgentvascular imaging (ultrasound, CT-angiography, or MRangiography) is recommended (Class I, Level A)



D i a g n o s

t i c s


Other Diagnostics


In patients with acute stroke and TIA, early evaluation of physiological parameters, routine blood tests, andelectrocardiography (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)



D i a g n o s

t i c s


Other Diagnostics


For stroke and TIA patients seen after the acute phase,24-hour Holter ECG monitoring should be performedwhen 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 testsis recommended

Echocardiography is recommended in selected patients(Class III, Level B)




ESO Guidelines 2008


– Stroke Unit




– Rehabilitation



P r i m a r y P r e

v e n t i o n


Primary Prevention

• Content – Management of vascular risk factors

– Antithrombotic therapy

– Carotid surgery and angioplasty



P r i m a r y P r e

v e n t i o n


Vascular Risk Factors

• Conditions and lifestyle characteristics identifiedas a risk factors for stroke

High blood pressure High Cholesterol

Atrial fibrillation Hyper-homocysteinaemiaDiabetes mellitus Smoking

Carotid artery disease Heavy alcohol use

Myocardial infarction Physical inactivity

Obesity



P r i m a r y P r e

v e n t i o n


High blood pressure (BP)

• Background – High blood pressure (>120/80mmHg) is the most

important and prevalent modifiable risk factor for stroke

– Significant reduction of stroke incidence with adecrease 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) 356:1955-642: Dahlof B et al. Lancet (2002) 359:995-1003.3: Mancia G et al. Eur Heart J (2007) 28:1462-536



P r i m a r y P r e

v e n t i o n


• Background – Independent risk factor for ischaemic stroke

– 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

Diabetes mellitus

1: Turner RC et al. JAMA (1999) 281:2005-122: Mancia GJ: Hypertens Suppl (2007) 25:S7-123: Sever PS et al. Diabetes Care (2005) 28:1151-7



P r i m a r y P r e

v e n t i o n


• Background – Statin treatment reduces the incidence of stroke from

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)

High Cholesterol

1: Amarenco P et al.: Stroke (2004) 35:2902-29092: HPS Group: Lancet (2002) 360:7-22.



P r i m a r y P r e

v e n t i o n


• Background – Independent risk factor for ischaemic stroke in men

and women

– 2-3 fold increased risk compared to non-smokers1

– Spousal cigarette smoking may be associated with anincreased stroke risk2

– 50% risk reduction by 2 years after stopping smoking3

Cigarette Smoking

1: Shinton R et al.: BMJ (1989) 298:789-94.2: Qureshi A et al.: Stroke (2005) 36:74-763: Colditz GA et al.: N Engl J Med (1988) 318:937-41.



P r i m a r y P r e

v e n t i o n


• Background – Increased risk for both ischaemic (RR 1.69) and

haemorrhagic stroke (RR 2.18) with heavy alcoholconsumption (>60g/day)1

– BP elevation might be a reasonable explanation3

– Light alcohol consumption (<12g/day) associated withreduced ischaemic (RR 0.80) and haemorrhagic

stroke1

– Red wine consumption carries the lowest risk2

Alcohol Consumption

1: Reynolds K et al.: JAMA (2003) 289:579-882: Mukamal K et al.: Ann Intern Med (2005) 142:11-193: Bazzano LA et al.: Ann Neurol (2007)



P r i m a r y P r e

v e n t i o n


• Background – Regular exercise (at least 3x30min/week) is

associated with a decreased risk of stroke

– Physically active individuals have a lower risk of strokeor death than those with low activity (RR 0.73)1

– This is mediated, in part, through beneficial effects onbody weight, blood pressure, serum cholesterol, and

glucose tolerance2

Physical Activity

1: Lee C et al.: Stroke (2003) 34:2475-24812: Deplanque D et al.: Neurology (2006) 67:1403-1410)



P r i m a r y P r e

v e n t i o n


Body Weight, Diet, Nutrition

• Background – High body mass index (BMI ≥25) increases risk of

stroke in men and women1

– Abdominal adiposity is a risk factor for stroke in menbut not women2

– A randomized trial in women found no effect of dietaryinterventions to reduce the incidence of stroke3

– Tocopherol and beta carotene supplementation do notreduce the risk of stroke. Vitamin E might increasemortality when used at high-dose (≥400 IU/d)

1: Kurth T et al.: Circulation (2005) 111:1992-19982: Hu G et al.: Arch Intern Med (2007) 167:1420-14273: Howard B et al.: JAMA (2006) 295:655-666



P r i m a r y P r e

v e n t i o n


• Background – Stroke rates rise rapidly in women after the

menopause

– Hormone replacement therapy in postmenopausalwomen is associated with an 44% increased risk of stroke1

Hormone Replacement Therapy

1: Gabriel S et al.: Cochrane Review (2005) CD002229



P r i m a r y P r e

v e n t i o n


Risk Factor Management

Recommendations (1/4) Blood pressure should be checked regularly. High blood

pressure should be managed with lifestyle modificationand individualized pharmacological therapy (Class I,

Level A) aiming at normal levels of 120/80 mmHg (Class

IV, GCP)



P r i m a r y P r e

v e n t i o n



Recommendations (2/4) Blood glucose should be checked regularly. Diabetes

should be managed with lifestyle modification andindividualized pharmacological therapy (Class IV, Level

C).

In diabetic patients, high blood pressure should bemanaged intensively (Class I, Level A) aiming for levels

below 130/80 mmHg (Class IV, Level C). Wherepossible, treatment should include an angiotensinconverting enzyme inhibitor or angiotensin receptor antagonist (Class I, Level A)



P r i m a r y P r e v e n t i o n



Recommendations (3/4) Blood cholesterol should be checked regularly. High

blood cholesterol (e.g. LDL>150mg/dl [3,9mMol/l]) shouldbe 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)






Recommendations (4/4) A diet low in salt and saturated fat, high in fruit and

vegetables and rich in fibre is recommended (Class III,

Level B)

Subjects with an elevated body mass index arerecommended 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)





• Background – In low risk persons low dose aspirin reduced coronary

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 asymptomaticcarotid artery disease3

Antithrombotic Therapy

1: Bartolucci A et al.: Am J Cardiol (2006) 98:746-7502: Berger J et al.: JAMA (2006) 295:306-3133: Hobson R, 2nd et al.: J Vasc Surg (1993) 17:257-263





• Background – Average stroke rate of 5% per year

– Aspirin reduces stroke (RR 0.78) in patients with non-valvular AF1

– Warfarin (INR 2.0-3.0) is more effective than aspirin atreducing 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

Atrial fibrillation (AF)

1: Hart RG et al.: Ann Intern Med (2007) 146:857-8672: Connolly S et al.: Lancet (2006) 367:1903-1912





• Background – Anticoagulation with an INR below 2.0 is not effective

– 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

Atrial fibrillation (AF)

1: Rash A et al.: Age Ageing (2007) 36:151-1562: Mant J et al.: Lancet (2007) 370:493-503






Recommendations (1/4) Low-dose aspirin is recommended in women aged 45

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 theprimary prevention of myocardial infarction; however, itdoes not reduce the risk of ischaemic stroke (Class I,

Level A)






Recommendations (2/4) Antiplatelet agents other than aspirin are not

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 oralanticoagulant (international normalized ratio [INR] 2.0-3.0) is recommended for patients with non-valvular AFwho are aged 65-75 years and free of vascular risk

factors (Class I, Level A)






Recommendations (3/4) Unless contraindicated, an oral anticoagulant (INR 2.0 –

3.0) is recommended for patients with non-valvular AFwho 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)






Recommendations (4/4) Patients with AF who are unable to receive oral

anticoagulants should be offered aspirin (Class I, Level

A)

Patients with AF who have mechanical prosthetic heartvalves should receive long-term anticoagulation with atarget INR based on the prosthesis type, but not less thanINR 2 –3 (Class II, Level B)

Low dose aspirin is recommended for patients withasymptomatic internal carotid artery (ICA) stenosis >50%to reduce their risk of vascular events (Class II, Level B)

Asymptomatic carotid artery





• Background1,2

– Carotid endarterectomy (CEA) is still a matter of 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%

Asymptomatic carotid artery(ICA) stenosis

1: ACAS: JAMA (1995) 273:1421-8.

2: ACST: Lancet (2004) 363:1491-1502

Asymptomatic carotid artery





• Specific issues – No prospective trials tested the benefit of antiplatelet

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 donot benefit from endarterectomy3

– Women have lower benefit from CEA than men3

– Aspirin reduces stroke risk during and after CEA4

Asymptomatic carotid artery(ICA) stenosis

1: Chambers BR et al.: Cochrane Review (2005)2: ECST Group: Lancet (1995) 345:209-123: Baker WH et al.: Stroke (2000) 31:2330-4

4: Engelter S et al.: Cochrane Reviews (2003)





Carotid Surgery and Angioplasty

Recommendations Carotid surgery is not recommended for asymptomatic

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 notrecommended for patients with asymptomatic carotidstenosis (Class IV, GCP)

Patients should take aspirin before and after CEA (Class

I, Level A)



S e c o n d a r y P

r e v e n t i o n


Secondary Prevention

• Content – Management of vascular risk factors

– Antithrombotic therapy

– Surgery and angioplasty



S e c o n d a r y P

r e v e n t i o n


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 baselineBP and type of stroke2

1: Rashid P et al.: Stroke (2003) 34:2741-82: PROGRESS group: Lancet (2001) 358:1033-41



S e c o n d a r y P

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• 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 endpoint of death and major vascular events (HR 0.78;95%CI 0.60-1.02; P=0.067)1

Diabetes mellitus

1: Wilcox R et al.: Stroke (2007) 38:865-73



S e c o n d a r y P

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• Background – Atorvastatin (80mg) reduces stroke recurrence by

16%1

– Simvastatin (40mg) reduces risk of vascular events inpatients with prior stroke, and of stroke in patients withother 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 beharmful3

High Cholesterol

1: Amarenco P et al.: N Engl J Med (2006) 355:549-5592: Heart Protection Study: Lancet (2002) 360:7-22

3: Blanco M et al.: Neurology (2007) 69:904-10



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• Background – Beta carotene increased the risk (RR 1.10) of

cardiovascular death1

– Antioxidant supplements may increase mortality2

– Folate, B12, B6 vitamins given to lower homocysteinelevels may not reduce stroke recurrence and mayincrease vascular events3

Vitamins

1: Vivekananthan D et al.: Lancet (2003) 361:2017-20232: Bjelakovic G et al.: JAMA (2007) 297:842-857

3: Bonaa K et al.: N Engl J Med (2006) 354:1578-1588



S e c o n d a r y P

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• Background – Oestrogen therapy is not effective in secondary

prevention after TIA or stroke and may increase strokeseverity1

Hormone Replacement Therapy

1: Viscoli CM et al.: N Engl J Med (2001) 345:1243-9.



S e c o n d a r y P

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• Background – Sleep-disordered breathing (SDB) is both a risk factor

and a consequence of stroke

– More than 50% of stroke patients have SDB, mostly inthe form of obstructive sleep apnoea (OSA).

– SDB is linked with poorer long-term outcome andincreased long-term stroke mortality1

– Continuous positive airway pressure is the treatment of choice for OSA.

Sleep-disordered Breathing

1: Bassetti CL: Semin Neurol (2005) 25:19-32



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Recommendations (1/3) 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. Diabetesshould be managed with lifestyle modification andindividualized pharmacological therapy (Class IV, GCP)

In patients with type 2 diabetes who do not need insulin,treatment with pioglitazone is recommended after stroke(Class III, Level B)



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Recommendations (2/3) 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)



S e c o n d a r y P

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Recommendations (3/3) 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 continuouspositive airway pressure breathing (Class III, Level GCP)

A i h b i Th



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• 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 dosedependent

– No difference in effectiveness amongst low (< 160mg),

medium (160 – 325mg) or high (500 - 1500mg) doseaspirin

1: Antithrombotic Trialists' Collaboration: BMJ (2002) 324:71-86

A tith b ti Th



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• Background: Dipyridamole plus aspirin – Relative risk reduction of vascular death, stroke or

myocardial infarction with the combination issignificantly 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) 143:1-132: Halkes P et al.: Lancet (2006) 367:1665-1673

3: Chang YJ et al.: Cerebrovasc Dis (2006) 22:258-62

A tith b ti Th



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• 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

A tith b ti Th



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• Background: Clopidogrel: – Clopidogrel is slightly but significantly more effective

than medium-dose aspirin (RRR 8.7%, ARR 0,5%) inpreventing vascular events in patients with previous

stroke, MI or PAD1

1: CAPRIE Steering Committee: Lancet (1996) 348:1329-1339

A tith b ti Th



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• Background: Clopidogrel plus aspirin – Compared with clopidogrel the combination of aspirin

and clopidogrel does not reduce the risk of ischaemicstroke, myocardial infarction, vascular death, or re-

hospitalisation1

– Compared with aspirin alone the combination does notreduce the risk of myocardial infarction, stroke, or cardiovascular death2

– Risk of life-threatening or major bleeding isincreased1,2

1: Diener H et al.: Lancet (2004) 364:331-337

2: Bhatt D et al.: N Engl J Med (2006) 354:1706-1717

A tith b ti Th



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Recommendations (1/4) Patients should receive antithrombotic therapy (Class I,

Level A)

Patients not requiring anticoagulation should receiveantiplatelet therapy (Class I, Level A). Where possible,combined aspirin and dipyridamole, or clopidogrel alone,should be given. Alternatively, aspirin alone, or triflusalalone, may be used (Class I, Level A)

A tith b ti Th



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Recommendations (2/4) 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 9months after the event (Class I, Level A)

Patients who have a stroke on antiplatelet therapy shouldbe re-evaluated for pathophysiology and risk factors(Class IV, GCP)

A ti l ti



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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 prostheticvalve replacement, rheumatic valvular heart disease,ventricular aneurysm and cardiomyopathy

– There is no indication for oral anticoagulation inpatients 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

A ti l ti



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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, fusiformbasilar 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) 152:967-732: Dressler FA et al.: J Am Coll Cardiol (1998) 31:134-83: Echiverri HC et al.: Stroke (1989) 20:1741-74: Engelter ST et al.: Stroke (2007) 38:2605-11

5: Mas JL et al.: N Engl J Med (2001) 345:1740-6

A tith b ti Th



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Recommendations (3/4) Anticoagulation should not be used after non-cardio-

embolic ischaemic stroke, except in some specificsituations, such as aortic atheromas, fusiform aneurysms

of the basilar artery, cervical artery dissection, or patentforamen ovale in the presence of proven deep veinthrombosis (DVT) or atrial septal aneurysm (Class IV,

GCP)

If oral anticoagulation is contraindicated, combined lowdose aspirin and dipyridamole should be given (Class IV,

GCP)




S e c o n d a r y P

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Recommendations (4/4) 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 acontraindication to oral anticoagulation (Class I, Level A)

Patients with cardioembolic stroke unrelated to AF shouldreceive anticoagulants (INR 2.0-3.0) if the risk of recurrence is high (Class III, Level C)

Carotid Endarterectomy (CEA)



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r e v e n t i o n


Carotid Endarterectomy (CEA)

• Background1,2

– CEA reduces the risk by 48% of recurrent disablingstroke or death in patients with 70-99%NASCET

ipsilateral carotid artery stenosis

– If perioperative complications exceed 6%, the benefitof CEA will diminish; if it approaches 10%, the benefitwill vanish entirely

– There is also some risk reduction in male patients with50 - 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

Carotid Endarterectomy



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• Specific issues

– CEA should be performed as soon as possible (ideallywithin 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% shouldundergo CEA. Women with moderate stenosis should

be treated medically

2

1: Rothwell PM et al.: Lancet (2004) 363:915-924

2: Rothwell PM et al.: Stroke (2004) 35:2855-61




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Effect of time from lastsymptomatic event torandomisation on the 5-year relative risk (RR) of

ipsilateral ischaemicstroke and any operativestroke or death with CEA(pooled data from ECST

and NASCET1)

1: Rothwell PM et al.: Stroke (2004) 35:2855-61




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• 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)



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Carotid Artery Stenting (CAS)

• Background

– No randomized trial has demonstrated equivalentperiprocedural risk for CAS compared to CEA intreatment of symptomatic carotid artery stenosis

– A European study only marginally failed to prove thenon-inferiority of CAS compared to CEA

– A French study was stopped prematurely because of a2.5 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

Carotid Artery Stenting



S e c o n d a r y P r e v e n t i o n


Carotid Artery Stenting

Metaanalysis CAS vs. CEAEndpoint: any periprocedural stroke or death

1: Kastrup A et al.: Acta Chir Belg (2007) 107:119-28

Intracranial Occlusive Disease





Intracranial Occlusive Disease

• Background – Extracranial-Intracranial bypass is not beneficial in

preventing stroke in patients with MCA or ICA stenosisor occlusion1

– No randomized controlled trials have evaluatedangioplasty, stenting, or both for intracranial stenosis

– Several non-randomized trials have shown feasibilityand acceptable safety of intracranial stenting, but therisk of re-stenosis remains high2,3

1: The EC/IC Bypass Grp: N Engl J Med (1985) 313:1191-2002: Bose A et al.: Stroke (2007) 38:1531-7

3: SSYLVIA Study investigators: Stroke (2004) 35:1388-92

Surgery and Angioplasty






Recommendations (1/4) CEA is recommended for patients with 70 –99% stenosis

(NASCET criteria) (Class I, Level A). CEA should only beperformed 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 thelast ischaemic event, ideally within 2 weeks (Class II,

Level B)







Recommendations (2/4) CEA may be indicated for certain patients with stenosis of

50 –69% (NASCET criteria); males with very recenthemispheric symptoms are most likely to benefit (Class

III, Level C). CEA for stenosis of 50 –69% (NASCETcriteria) should only be performed in centres with aperioperative 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)







Recommendations (3/4) 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 followingsubgroups of patients with severe symptomatic carotidartery 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)







Recommendations (4/4) 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 patientswith symptomatic intracranial stenosis (Class IV, GPC)

ESO Guidelines 2008




ESO Guidelines 2008


– Stroke Unit




– Rehabilitation

General Stroke Treatment



G e n e r a l T r e a t m e n t



• Content – Monitoring

– Pulmonary and airway care

– Fluid balance

– Blood pressure

– Glucose metabolism

– Body temperature

Monitoring





Monitoring

• Continuous monitoring – Heart rate

– 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





Pulmonary function

• Background – Adequate oxygenation is important

– Improve blood oxygenation by administration of > 2 lO2

– Risk for aspiration in patients with side positioning

– Hypoventilation may be caused by pathologicalrespiration pattern

– Risk of airway obstruction (vomiting, oropharyngealmuscular hypotonia): mechanical airway protection

Blood pressure





Blood pressure

• Background – Elevated in most patients with acute stroke

– BP drops spontaneously during the first days after stroke

– Blood flow in the critical penumbra passivelydependent on the mean arterial pressure

– There are no adequately sized randomised, controlled

studies guiding BP management

Blood pressure





Blood pressure

• Specific issues – Elevated BP (e.g. up to 200mmHg systolic or

110mmHg diastolic) may be tolerated in the acutephase of ischaemic stroke without intervention

– BP may be lowered if this is required by cardiacconditions

– Upper level of systolic BP in patients undergoingthrombolytic therapy is 180mmHg

– Avoid and treat hypotension

– Avoid drastic reduction in BP

Glucose metabolism





Glucose metabolism

• Background – High glucose levels in acute stroke may increase the

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 moderatehyperglycaemia did not improve outcome1

• It is common practise to treat hyperglycemia with insulinwhen 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.

Body temperature



G e n e r a l T

r e a t m e n t


Body temperature

• Background – Fever is associated with poorer neurological outcome

after stroke

– Fever increases infarct size in experimental stroke

– Many patients with acute stroke develop a febrileinfection

• 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




G e n e r a l T

r e a t m e n t



Recommendations (1/4) Intermittent monitoring of neurological status, pulse, blood

pressure, temperature and oxygen saturation isrecommended 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 isrecommended in patients with severe stroke or swallowing problems (Class IV, GCP)




G e n e r a l T

r e a t m e n t



Recommendations (2/4) Normal saline (0.9%) is recommended for fluid

replacement during the first 24 hours after stroke (Class

IV, GCP)

Routine blood pressure lowering is not recommendedfollowing acute stroke (Class IV, GCP)

Cautious blood pressure lowering is recommended inpatients with any of the following; extremely high bloodpressures (>220/120 mmHg) on repeated measurements,or severe cardiac failure, aortic dissection, or hyper-tensive encephalopathy (Class IV, GCP)




G e n e r a l T

r e a t m e n t



Recommendations (3/4) Abrupt blood pressure lowering should be avoided (Class

II, Level C)

Low blood pressure secondary to hypovolaemia or

associated with neurological deterioration in acute strokeshould 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)




G e n e r a l T

r e a t m e n t



Recommendations (4/4) Severe hypoglycaemia (<50 mg/dl [<2.8 mmol/l]) should

be treated with intravenous dextrose or infusion of 10 –20% glucose (Class IV, GCP points)

The presence of pyrexia (temperature >37.5°C) shouldprompt a search for concurrent infection (Class IV, GCP)

Treatment of pyrexia (>37.5°C) with paracetamol andfanning is recommended (Class III, Level C)

Antibiotic prophylaxis is not recommended inimmunocompetent patients (Class II, Level B)

ESO Guidelines 2008





– Stroke Unit



– Acute Treatment

– Management of Complications

– Rehabilitation

Specific Stroke Treatment



S p e c i f i c T

r e a t m e n t


Specific Stroke Treatment

• Content – Thrombolytic therapy

– Early antithrombotic treatment

– Treatment of elevated intracranial pressure

– Prevention and management of complications

Thrombolytic Therapy (i.v. rtPA)



S p e c i f i c T

r e a t m e n t



• Background (NINDS1, ECASS I2 + II3, ATLANTIS4) – Intravenous rtPA (0.9mg/kg, max 90mg) given within 3

hours of stroke onset, significantly improves outcomein patients with acute ischaemic stroke

– Benefit from the use of i.v. rtPA beyond 3 hours issmaller, but may be present up to at least 4.5 hours

– Several contraindications

1: NINDS rt-PA Grp: New Engl J Med (1995) 333:1581-15872: Hacke W et al.: JAMA (1995) 274:1017-10253: Hacke W et al.: Lancet (1998) 352:1245-1251

4: Clark WM et al.: Jama (1999) 282:2019-26.




S p e c i f i c T

r e a t m e n t



• Specific issues – A pooled analysis of the 6 i.v. rtPA trials confirms that

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 CTdemonstrates extended early infarcts signs

– Thrombolytic therapy must be given by an experiencedstroke physician after the imaging of the brain isassessed by physicians experienced in reading thisimaging study2

1: Hacke W et al.: Lancet (2004) 363:768-74

2: Wahlgren N et al.: Lancet (2007) 369:275-82




S p e c i f i c T

r e a t m e n t


y py ( )

• Specific issues – Factors associated with increased bleeding risk1

• 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




S p e c i f i c T

r e a t m e n t


y py ( )

Risk and outcome from 6,483 patients of the SITS-Mosttreated with iv-rtPA within a 3 hour time window1

1: Wahlgren N et al.: Lancet (2007) 369:275-82




S p e c i f i c T

r e a t m e n t


y py ( )

• Mismatch based therapy – The use of multimodal imaging criteria may be useful

for patient selection1,2

– Available data on mismatch, as defined by multimodal

MRI or CT, are too limited to guide thrombolysis inroutine practice3

– Data regarding the use of intravenous desmoteplaseadministered 3 to 9 hours after acute ischaemic strokein patients selected on the basis of perfusion/diffusionmismatch are conflicting

1: Köhrmann M et al.: Lancet Neurol (2006) 5:661-72: Chalela J et al.: Lancet (2007) 369:293-298

3: Kane I et al.: JNNP (2007) 78:485-490

Thrombolytic Therapy (i.a.)



S p e c i f i c T

r e a t m e n t


y py ( )

• Background: the use of i.a. rtPA, i.a. urokinase – Only cases and some prospective uncontrolled case

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

Specific Treatment



S p e c i f i c T

r e a t m e n t


p

Recommendations (1/5) Intravenous rtPA (0.9 mg/kg BW, maximum 90 mg), with

10% of the dose given as a bolus followed by a 60-minuteinfusion, 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 beuseful for patient selection (Class III, Level C)

Specific Treatment



S p e c i f i c T

r e a t m e n t


p

Recommendations (2/5) Blood pressures of 185/110 mmHg or higher must be

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 acutecerebral ischaemia (Class IV, GCP)

Intravenous rtPA may also be administered in selectedpatients over 80 years of age, although this is outside thecurrent European labelling (Class III, Level C)

Specific Treatment



S p e c i f i c T

r e a t m e n t


p

Recommendations (3/5) Intra-arterial treatment of acute MCA occlusion within a 6-

hour time window is recommended as an option (Class II,

Level B)

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

B)

Antiplatelet therapy



S p e c i f i c T

r e a t m e n t


p py

• Background – Aspirin was tested in large RCTs in acute (<48 h)

stroke1,2

– Significant reduction was seen in death and

dependency (NNT 70) and recurrence of stroke (NNT140)

– A phase 3 trial for the glycoprotein-IIb-IIIa antagonistabciximab was stopped prematurely because of anincreased rate of bleeding3

1: International-Stroke-Trial: Lancet (1997) 349:1569-15812: CAST-Collaborative-Group: Lancet (1997) 349:1641-1649

3: Adams HP, Jr. et al.: Stroke (2007)

Anticoagulation



S p e c i f i c T

r e a t m e n t


g

• Unfractionated heparin – No formal trial available testing standard i.v. heparin

– IST showed no net benefit for s.c. heparin treatedpatients 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.



Specific Treatment



S p e c i f i c T

r e a t m e n t


Recommendations (4/5) Aspirin (160 –325 mg loading dose) should be given within

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 within24 hours (Class IV, GCP)

The use of other antiplatelet agents (single or combined)is not recommended in the setting of acute ischaemicstroke (Class III, Level C)

The administration of glycoprotein-IIb-IIIa inhibitors is notrecommended (Class I, Level A)

Specific Treatment



S p e c i f i c T

r e a t m e n t


Recommendations (5/5) Early administration of unfractionated heparin, low

molecular weight heparin or heparinoids is notrecommended 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



S p e c i f i c T

r e a t m e n t


• Basic management – Head elevation up to 30°

– 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.




S p e c i f i c T

r e a t m e n t


• Malignant MCA/hemispheric infarction – Pooled analysis of three European RCTs (N=93)1,2:

• Significantly decreases mortality after 30 days

• Significantly more patients with mRS <4 or mRS <3in 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) 6:215-222: Jüttler E et al.: Stroke (2007) 38:2518-25

3: Gupta R et al.: Stroke (2004) 35:539-43




S p e c i f i c T

r e a t m e n t


Absolute risk reduction (ARR) and odds ratio (OR) for unfavourableoutcome at 12 months: combined analysis of decompression trials1

1: Vahedi K et al.: Lancet Neurol (2007) 6:215-22




S p e c i f i c T

r e a t m e n t


Recommendations (1/2) Surgical decompressive therapy within 48 hours after

symptom onset is recommended in patients up to 60years 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)




S p e c i f i c T

r e a t m e n t


Recommendations (2/2) No recommendation can be given regarding hypothermic

therapy in patients with space-occupying infarctions(Class IV, GCP)

Ventriculostomy or surgical decompression can beconsidered for treatment of large cerebellar infarctionsthat compress the brainstem (Class III, Level C)



Management of Complications



S p e c i f i c T

r e a t m e n t


• Aspiration and pneumonia – Bacterial pneumonia is one of the most important

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




S p e c i f i c T

r e a t m e n t


• Urinary tract infections – Most hospital-acquired urinary tract infections are

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




S p e c i f i c T

r e a t m e n t


• Deep vein thrombosis and pulmonary embolism – Risk might be reduced by good hydration and early

mobilization

– Low-dose LMWH reduces the incidence of both DVT

(OR 0.34) and pulmonary embolism (OR 0.36), withouta 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




S p e c i f i c T

r e a t m e n t


• Pressure ulcer – Use of support surfaces, frequent repositioning,

optimizing nutritional status, and moisturizing sacralskin 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




S p e c i f i c T

r e a t m e n t


• Falls – Are common in every stage of stroke treatment

– Risk factors include cognitive impairment, depression,polypharmacy and sensory impairment1

– A multidisciplinary package focusing on personal andenvironmental factors might be preventive2

– Exercise, calcium supplements and bisphosphonatesimprove bone strength and decrease fracture rates instroke patients3,4

1: Aizen E et al.: Arch Gerontol Geriatr (2007) 44:1-122: Oliver D et al.: BMJ (2007) 334:823: Pang MY et al.: Clin Rehabil (2006) 20:97-111

4: Sato Y et al.: Cerebrovasc Dis (2005) 20:187-92




S p e c i f i c T

r e a t m e n t


• Dysphagia and feeding – Dysphagia occurs in up to 50% of patients with

unilateral hemiplegic stroke and is an independentrisk-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) 36:2756-632: Dennis MS et al.: Lancet (2005) 365:764-72

3: Callahan CM et al.: J Am Geriatr Soc (2000) 48:1048-54




S p e c i f i c T

r e a t m e n t


Recommendations (1/4) Infections after stroke should be treated with appropriate

antibiotics (Class IV, GCP)

Prophylactic administration of antibiotics is not

recommended, and levofloxacin can be detrimental inacute stroke patients (Class II, Level B)

Early rehydration and graded compression stockings arerecommended to reduce the incidence of venous

thromboembolism (Class IV, GCP)

Early mobilization is recommended to prevent compli-cations such as aspiration pneumonia, DVT and pressureulcers (Class IV, GCP)




S p e c i f i c T

r e a t m e n t


Recommendations (2/4) Low-dose s.c. heparin or low molecular weight heparins

should be considered for patients at high risk of DVT or pulmonary embolism (Class I, Level A)

Administration of anticonvulsants is recommended toprevent recurrent seizures (Class I, Level A)

Prophylactic administration of anticonvulsants to patientswith recent stroke who have not had seizures is not

recommended (Class IV, GCP)

An assessment of falls risk is recommended for everystroke patient (Class IV, GCP)




S p e c i f i c T

r e a t m e n t


Recommendations (3/4) Calcium/vitamin-D supplements are recommended in

stroke patients at risk of falls (Class II, Level B)

Bisphosphonates (alendronate, etidronate and

risedronate) are recommended in women with previousfractures (Class II, Level B)

In stroke patients with urinary incontinence, specialistassessment and management is recommended (Class

III, Level C)

Swallowing assessment is recommended but there areinsufficient data to recommend a specific approach for treatment (Class III, GCP)




S p e c i f i c T

r e a t m e n t


Recommendations (4/4) Oral dietary supplements are only recommended for non-

dysphagic stroke patients who are malnourished (Class

II, Level B)

Early commencement of nasogastric (NG) feeding (within48 hours) is recommended in stroke patients withimpaired 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





– Stroke Unit

– Imaging and Diagnostics

– Prevention


– Acute Treatment

– Management of Complications

– Rehabilitation

Rehabilitation



R e h a b

i l i t a t i o n


• Early rehabilitation – More than 40 % of stroke patients need active

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 asperceptable recovery is taking place

Rehabilitation



R e h a b

i l i t a t i o n


• Multidisciplinary stroke team for rehabilitation – Stroke physician

– Nurses experienced in stroke management

– Physiotherapist trained in stroke rehabilitation

– Occupational therapist skilled in stroke

– Speech therapist familiar with speech problems instroke patients

– Neuropsychologist accustomed to stroke rehabilitation – Social worker familiar with the problems of stroke

patients

Setting of Rehabilitation



R e h a b

i l i t a t i o n


Recommendations (1/2) Admission to a stroke unit is recommended for acute

stroke patients to receive coordinated multidisciplinaryrehabilitation (Class I, Level A)

Early discharge from stroke unit care is possible inmedically stable patients with mild or moderateimpairment providing that rehabilitation is delivered in thecommunity by a multidisciplinary team with stroke

expertise (Class I, Level A)

Setting of Rehabilitation



R e h a b

i l i t a t i o n


Recommendations (2/2) Rehabilitation should be continued after discharge during

the first year after stroke (Class II, Level A)

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



R e h a b

i l i t a t i o n


Recommendations (1/3) Physiotherapy is recommended, but the optimal mode of

delivery is unclear (Class I, Level A)

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 recommendspecific treatments (Class III, GCP)

Information should be provided to patient and carers butevidence does not support use of a dedicated strokeliaison service for all patients (Class II, Level B)

Elements of Rehabilitation



R e h a b

i l i t a t i o n


Recommendations (2/3) Rehabilitation must be considered for all stroke patients,

but there is limited evidence to guide appropriatetreatment for the most severely disabled (Class II, Level

B) While assessment for cognitive deficits appears

desirable, there are insufficient data to recommendspecific treatments (Class I, Level A)

Patients should be monitored for depression duringhospital stay and throughout follow up (Class IV, Level

B)

ESO08 Slides 25thApril

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