Eusi Stroke

- SYMPOSIUM

RECOMMENDATIONS FOR STROKE MANAGEMENT

European Federation of Neurological SocietiesEFNS Copenhagn 2000


• Part 1: Organizing Modern Stroke CareTom Skyhoj Olsen, Copenhagn (DEN)

• Part 2: Risk Factors and Primary PreventionJulien Bogousslavsky, Lausanne (SUI)

• Part 3: Acute Stroke Care - General TherapyMarkku Kaste, Helsinki (FIN)

• Part 4: Acute Stroke Care - Specific TherapyWerner Hacke, Heidelberg (GER)

• Part 5: Rehabilitation and Secondary PreventionJean-Marc Orgogozo, Bordeaux (FRA)


• Part 1: Organizing Modern Stroke CareTom Skyhoj Olsen, Copenhagn (DEN)


• Part 2: Risk Factors and Primary PreventionJulien Bogousslavsky, Lausanne (SUI)


• Part 3: Acute Stroke Care - General TherapyMarkku Kaste, Helsinki (FIN)


• Part 4: Acute Stroke Care - Specific TherapyWerner Hacke, Heidelberg (GER)


• Part 5: Rehabilitation and Secondary PreventionJean-Marc Orgogozo, Bordeaux (FRA)

Definitions of Levels of Evidencemodified from Adams et al. 1994

• Level I: Highest Level of Evidence

Sources: a) Primary endpoint of double blind RCT with adequate sample size

b) Meta-analysis of qualitatively outstanding RCTs

• Level II: Intermediate Level of Evidence

Sources: a) Randomised not blinded trials

b) Small randomised trials

c) Predefined secondary endpoints of large RCTs

• Level III: Lower Level of Evidence

Sources: a) Prospective case series with concurrent or historical control

b) Post hoc analyses of large RCTs

• Level IV: Undetermined Level of Evidence

Sources: a) Small uncontrolled case series

b) General agreement despite lack of evidence

Acute Stroke Care-Emergency Diagnostic Tests

• Differentiation between different types of stroke• Ruling out other brain diseases• Assessing the underlying cause of brain ischemia• Providing a basis for physiological monitoring of

the stroke patient• Identifying concurrent diseases or complications

associated with stroke

Emergency Diagnostic Tests

• Cranial computed tomography (CCT)– distinguishes reliably between hemorrhagic and

ischemic stroke– early signs of ischemia detected as early as 2 h

after stroke onset– identifies hemorrhages almost immediately– detects SAH in the majority of cases– helps to identify other neurological diseases

(e.g. neoplasms)


• Magnetic resonance imaging (MRI)– only helpful in centres using modern MRI

techniques– diffusion- and perfusion-weighted MRI may help

to differentiate between infarcted tissue and tissue at risk


• Electrocardiogram– high incidence of heart involvement in stroke

patients– coincidence of stroke and myocardial infarction– ischemic stroke may cause arrhythmias– detection of atrial fibrillation as a possible cause

of embolic stroke


• Ultrasound studies– cw/pw- Doppler and/or duplex sonography of

the extracranial cervical and the basal intracranial arteries

• identification of vessel stenosis, occlusion, state of collaterals, or recanalisation

– transesophageal echocardiography to screen for cardiogenic emboli (not in the ER but recommended within the first 24 h after stroke onset)


• Laboratory tests– hematology– clotting parameters– electrolytes– renal and hepatic chemistry– cardiac enzymes– basic parameters of infection


• EUSI Recommendations

1. CCT is the most important diagnostic tool in patients with suspected stroke (Level IV)

2.Early evaluation of physiological parameters, blood chemistry and hematology, and cardiac function (ECG, pulsoximetry, chest x-ray) is recommended in the management of acute stroke patients



3. Cardiac and Neurological ultrasound should be readily available (Level IV)

Acute Stroke Care-General Management

• EUSI-recommendations include– Pulmonary and airway care– Blood pressure– Body temperature– Glucose metabolism– Fluid and electrolyte management

General Management

• Monitoring of vital and neurological functions– continuous monitoring:

• heart rate

• O2 saturation

– discontinuous monitoring• Blood pressure (e.g. automatic inflatable

sphygmomanometry)• Clinical: Vigilance / GCS, pupils• Neurological (e.g. NIH and Scandinavian stroke

scale)

General treatment

• Pulmonary function and airway protection– Adequate oxygenation important for preservation of the

penumbra– Improved blood oxygenation by administration of > 2 l O2

(SO2 -guided)– Risk for aspiration in patients with pseudobulbar/bulbar

paralysis and reduced vigilance: side positioning, consider tracheotomia

– Consider hypoventilation by pathological respiration pattern

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

General treatment

• Blood pressure (BP)– elevated in most of the patients with acute

stroke– Flow in the critical penumbra passively

dependent on the mean arterial pressure– Sufficient post-stenotic flow requires high blood

pressure

General treatment

• Blood pressure– There are no controlled, randomised studies

guiding BP management• Recommended target BP in patients with prior

hypertension: 180 / 100-105 mmHg• Recommended target BP in previously normotonic

patients: 160-180 / 90-100 mmHg• Avoid and treat hypotension or drastic reductions in

BP

General treatment

• Blood pressure– Indications for immediate antihypertensive

therapy in acute stroke:• Non-ischemic cause for stroke• Cardiac insufficiency• Aortic dissection• Acute renal failure• Hypertensive encephalopathy

General treatment

• Body temperature– Facts

• Fever negatively influences neurological outcome after stroke

• Experimentally, fever increases infarct size• Many patients with acute stroke develop a febrile

infection after stroke– Although no controlled trial supporting treatment of an

elevated temperature, consider to treat fever when the body temperature reaches 37.5°C rectally

General treatment

• Glucose metabolism– Facts

• Pre-existent diabetic metabolic derangement can be worsened

• High glucose levels in the acute phase of stroke may increase the size of the infarction and reduce functional outcome

• Hypoglycemia worsens outcome as well• Hypoglycemia can mimic an acute ischemic

infarction

General treatment

• Fluid and electrolyte management– Serious electrolyte abnormalities are rare after

ischemic stroke but frequent after ICH and SAH– Balanced electrolyte and fluid status are

important to avoid:• plasma volume contraction• raised hematocrit• impaired rheologic properties

General treatment


1. Neurological status and vital functions should be monitored

2. Glucose and body temperature should be monitored and corrected, if elevated (Level III)

3. Do not treat hypertension in patients with ischemic stroke, if they do not have critically elevated BP levels (Level III)

General treatment


4. Secure airways and supply oxygen to patients with severe acute stroke (Level IV)

5. Monitoring and correction of electrolyte and fluid disturbances are advised (Level IV)

Acute Stroke Care-Specific Treatment

• EUSI-recommendations include– Acute anti-thrombotic therapy

• Thrombolytic therapy• Defibrinogenating enzymes• ASA

– Neuroprotection– Treatment of elevated ICP and brain edema

• Medical treatment• Surgical treatment

Thrombolytic Therapy

• IV-Thrombolysis (rtPA)– Facts (NINDS Pt. 1 + 2, ECASS I + II, ATLANTIS)

• 3h time window approved in USA, CDN, MEX, I.V. 0.9mg/kg, max 90mg

• Not yet approved in Europe• Efficacy signal beyond 3h (meta-analysis)

• IV-Thrombolysis (SK)– Facts (MAST-I, MAST-E, AST)

• Although some efficacy signal in early time windwow, SK currently abandoned


• IA-Thrombolysis (rtPA, UK)– Facts

• Only cases and some prospective uncontrolled case series

• IA-Thrombolysis (rPUK)– Facts (PROACT I and II)

• Efficacy proven in small RCT, 6h window,• Not approved, PROACT III?


• EUSI Recommendations (for centers offering thrombolysis)

1. I.V. rtPA (0.9mg/kg; max 90mg, 10% bolus, followed by 60 min infusion) is recommended within 3 hours after stroke onset (Level I)

2. The benefit from the use of I.V. rtPA beyond 3 hours is smaller, but present in selected patients (Level I)

3. I.V. rtPA is not recommended when time of onset is uncertain


• EUSI Recommendations (for centers offering thrombolysis)

4. I.V. SK outside of the setting of acontrolled clinical trial is dangerous and not indicated for the management of persons with ischemic stroke (Level I)

5. Intra-arterial treatment of acute M1 occlusion in a 6 h time window using rPUK results in a significantly improved outcome (Level II)

3. Acute BA-occlusion may be treted with I.A, therapy in selected centers (Level IV)

Defibrinogenating Therapy

• ANCROD– Treatment of acute ischemic stroke with I.V.

Ancrod in a 3 h time window results in significantly improved outcome (primary endpoint only (STAT)

– Futility analysis of 6 h trial (ESTAT) led to premature termination of the trial

Defibrinogenating Therapy

• EUSI Recommendation

1. Ancrod given in a 3 h time window significantly improves outcome after acute ischemic stroke (Level II)

Platelet Inhibitors

• ASA – only substance tested in acute (<48 h)

stroke (IST, CAST)

– CT not required for randomisation– small but significant reduction of mortality

and recurrence of stroke in combined analysis of both trials

Platelet Inhibitors

• EUSI-recommendation

1. Aspirin 100-300 mg/day may be given to an unselected stroke population (Level II)

Therapeutic Anticoagulation

• Unfractionated heparin – no formal trial available testing standard I.V.

heparin– IST showed no benefit for sc heparin treated

patients, increased risk of ICH• Low molecular weight heparins

– Postive effect seen in small pilot trial (Kay 1995) was not found in subsequent trial (fisBIS)

• Heparinoid (Orgaran)– TOAST trial negative

Therapeutic Antioagulation

• EUSI-recommendation 1. There is no recommendation for the general

use of heparin, low molecular weight heparines or heparinoids after ischemic stroke (Level I)

2. Full dose heparin may be used in selected indications such as AF, other cardiac sources with high risk of re-embolism, arterial dissection, or high grade arterial stenosis (Level IV)

3. Administration for DVT-prophylaxis see general treatment

Neuroprotection

• Up to now, not a single neuroprotective substance has been shown to influence outcome after stroke.

• Currently there is no recommendation to treat patients with neuroprotective drugs after ischaemic stroke (Level I)

Elevated Intracranial Pressure and Brain Edema Treatment

• Medical therapy – Basic management

• Head positioning <30°• Pain relief and sedation• Normothermia• Osmotic agents

– Glycerol– Mannitol– Hypertonic saline

• Barbiturates, hyperventilation and THAM-buffer


• Surgical Therapy– Ventricular drainage

• Posterior fossa space occupying infarction• Thalamic infarction (rare)

– Decompressive surgery• Posterior fossa space occupying infarctian• Malignant MCA/hemispheric infarction

– Encouraging reduction of mortality with decent outcome i prospective case series

– RCT (HEADFIRST) starts recruiting


• EUSI-recommendations

1. Osmotherapy is recommended for patients whose condition is deteriorating secondary to increased ICP, including those with herniation syndromes (Level III)

2. Surgical decompression of large cerebellar infarctions that compress the brainstem is justified (Level III)

3.Surgical decompression of large hemispheric infarction can be life-saving (Level III)

Stroke Units

• Definition:– Hospital or part of a hospital that (nearly)

exclusively takes care of stroke patients– Specialised staff with multidisciplinary approach

to treatment and care– Core disciplines: medical treatment, nursing,

physiotherapy, occupational therapy, speech and language therapy, social work

Stroke Units

• Facts (Stroke Unit Trialist´s Collaboration)

– Acute treatment in a stroke unit results in significant reduction in mortality, death, dependence, or need of institutional care in comparison to a general medical ward

Stroke Units

• Types of stroke units:1. Acute stroke unit

• acute treatment < 1 week (2-3 days)

2. Combined acute and rehabilitation stroke unit• acute phase + reha for several weeks / months

3. Rehabilitation stroke unit• admission after 1to 2 weeks after stroke onset

4. Mobile stroke team• offers stroke care and treatment on a variety of

wards

Stroke Units


1. Stroke patients should be treated in specialised stroke units (Level I)

Rehabilitation

• Early rehabilitation– 40% of stroke patients need active reha

services– active rehabilitation should start as soon as

possible– if the patient is unconscious, rehabilitation is

passive to prevent contractions and other immobilisation-associated complications

Rehabilitation

• Rehabilitation programs

- Assessment for the degree of disability (motor, cognitive, sensory, visual)

- Assessment of the ability to respond to rehabilitation (financial burden, chances to return to social activities and work and to live alone, need of help)

- adaptation of the intensity of the rehabilitation to status and the degree of disability

Rehabilitation

• Rehabilitation programs

- daily documentation of the patients progress

- teaching and involvement of the patient and his family members

- home visitation as early as possible (smoothing the transit, increasing motivation)

- planning the transfer to a specialised rehabilitation hospital if a longer reha period is expected

Rehabilitation

• ideal multidisciplinary stroke team for adequate rehabilitation

- stroke physician and nurses experienced in stroke management

- physiotherapist, speech therapist and occupational therapist trained in stroke rehabilitation

- neuropsychologist and social worker accustomed to stroke rehabilitation

Rehabilitation


1. Rehabilitation should be initiated early after stroke (Level I)

2. Every patient should have access to evaluation for rehabilitation (Level III)

3. Rehabilitation services should be provided by a multidisciplinary team (Level III)

Primary Prevention

• Conditions and lifestyle factors identified as a risk for stroke:– arterial hypertension– myocardial infarction– atrial fibrillation– diabetes mellitus– elevated cholesterol levels– carotid artery disease– smoking– alcohol use– physical activity

Primary Prevention

• Hypertension– Facts

• most prevalent and modifiable risk factor for stroke• significant reduction of stroke incidence with a

decrease of 5 mmHg in diastolic BP or teatment of isolated systolic BP elevation

Primary Prevention

• Diabetes mellitus

– Facts• independent risk factor for ischemic stroke• strict control of blood glucose not established for

stroke prevention• elevated blood glucose at stroke onset worsens

mortality and functional outcome

Primary Prevention

• Hypercholesterolemia– Facts

• no strong association between serum cholesterol levels and stroke

• reduction in the relative risk of stroke with pravastatin therapy

• reduction of stroke mortality by statin therapy: controversial

Primary Prevention

• Cigarette smoking

– Facts (Cohort studies)• independent risk factor for ischemic stroke in men

and women• 6-fold risk compared to non-smokers• 50% risk reduction by stop of smoking

Primary Prevention

• Alcohol consumption– decreased risk by moderate consumption (men:

20-30 mg/die)– increased risk for both ischemic and

hemorrhagic stroke by heavy alcohol consumption

Primary Prevention

• Physical activity– Facts

• vigorous exercise is associated with a decreased risk of stroke

– this effect may be mediated by reduction in body weight, BP, cholesterol and increased glucose tolerance

Primary Prevention

• Antithrombotic drugs– Facts

• trend to higher incidence of disabling strokes (hemorrhagic) by aspirin ingestion (325-500 mg/die) in males

• no risk alteration in women• risk reduction in MI for both men and women

Primary Prevention

• EUSI-recommendations 1. BP measurement should be an essential

component of regular health care visits; BP should be lowered to normal (140/85 mmHg) values by means of life-style and/or pharmacological treatment (Level I)

2. Although strict control of glucose or high cholesterol levels has not been proven to be associated with a decreased risk of stroke, it should be encouraged because of benefits in terms of other diseases (Level III)

Primary Prevention


3. In coronary patients, treatment with simvastatin or pravastatin clearly reduces the risk of stroke (Level II). Statins should be prescribed in patients with CHD and high or moderate cholesterol levels; the benefits of statins probably extend to patients with stroke and high cholesterol levels.

4. Cigarette smoking should be discouraged (Level II)

Primary Prevention


5. Heavy use of alcohol should be avoided, while moderate consumption may be permitted

(Level II)

6. Regular physical activity is recommended (Level II)

7. There is no scientific support for prescribing aspirin to reduce the risk of stroke in asymptomatic patients (Level I); however, aspirin may reduce the risk of MI (Level I)

Primary Prevention

• Atrial fibrillation (AF)– Facts

• average stroke rate of 5% per year• warfarin reduces the rate of ischemic strokes by 25 %• anticoagulation with an INR of 2.0 to 3.0 reduces the

rate of ischemic and hemorrhagic events by 80% when compared to below 2.0, where non-significant reduction in thromboembolic events is seen

• unacceptable risk for bleeding complications with an INR > 5.0

Primary Prevention

• Atrial fibrillation– Facts

• aspirin (300 mg) achieves a pooled risk reduction of 21 %

• aspirin is less efficacious than warfarin• patients less than 65 years of age with “lone AF” are

at low risk, whereas patients older than 65 years are at moderate risk for embolic stroke

Primary Prevention

• Atrial fibrillation: EUSI-recommendations

1. Long-term oral anticoagulation therapy (target INR 2.5; range 2.0 - 3.0) should be considered for all AF patients who are at high risk for stroke (Level I)

2. Patients aged less than 65 years with no cardiovascular disease or patients who are unable to receive anticoagulants should be offered 300 mg aspirin per day (Level I)

Primary Prevention

• Atrial fibrillation: EUSI-recommendations

3. Although not yet established by randomised studies, patients over 65 years of age without risk factors could be offered both AC and aspirin 300 mg/ day (Level III)

4. Although not yet established by randomised studies, patients over 75 years of age, warfarin may be used with a lower INR (target INR of 2.0; range 1.6. - 2.5) to decrease the risk of hemorrhage (Level III)

Primary Prevention

• Asymptomatic carotid artery stenosis– CEA is still a matter of controversy– 5-year relative risk reduction by CEA for carotid

artery stenosis >65% of 50% (absolute reduction about 6%)

– absolute risk reduction by medical treatment of 11%/ 5 years

Secondary Prevention

• Antithrombotic drugs– Aspirin: Facts

• 25% risk reduction• optimal dose still matter of debate• no proven advantage by low (< 160 mg) versus

medium (160 - 325) or high (500 - 1500 mg) doses


• Antithrombotic drugs– Dipyridamole + aspirin:

• ESPS II: risk reduction of stroke with a combination is significantly higher (37%) than with aspirin alone


• Antithrombotic drugs– Clopidogrel

• CAPRIE: Clopidogrel is slightly but significantly more effective than medium-dose aspirin



1. Low- or medium-dose ASA (50-325 mg) should be given as first-choice agent to reduce stroke recurrence (Level I).

2. Alternatively, where available, the combination of ASA (25 mg) and dipyridamole (200 mg) twice daily may be given as first choice (Level I)



3. Clopidogrel is slightly more effective than aspirin (Level I). It may be prescribed as first-choice or when aspirin is not tolerated or efficacious, and in special indications, such as in high-risk patients (Level III)



4. Patients starting treatment with thienopyridine derivatives should receive clopidogrel instead of ticlopidine since it has fewer side-effects

(Level I);

patients who have already been treated with ticlopidine for a long time should be maintained on this regimen because the most severe side-effects (neutropenia and rash) appear at the beginning of treatment



5. Patients who do not tolerate both ASA or clopidogrel may be treated with dipyridamol ret 2x200 mg daily (Level I)


• Anticoagulation after thromboembolic stroke– Facts (EAFT)

• oral anticoagulation with an INR of 2 - 3 reduces the risk of recurrent stroke in patients with AF

– Oral anticoagulation is well established for other causes of embolism such as mechanical prosthetic valve replacement, rheumatic valvular heart disease, ventricular aneurysm, cardiomyopathy, or PFO



1. Oral anticoagulation (INR 2.0 - 3.0) is indicated after stroke associated with

AF (Level I)

2. Patients with mechanical prosthetic valves should receive long-term anticoagulation therapy with a target INR between 3.0 and 4.0 (Level III)



3. Patients with proven cardioembolic stroke should be anticoagulated if the risk of recurrence is high, with a target INR between 2.0 and 3.0 (Level III)


• Carotid Endarterectomy (CEA)– Facts (NASCET, ECST)

• surgery is efficacious for symptomatic patients with ipsilateral carotid stenosis > 70%

• if perioperative complications exceed 2.5 %, 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


• Percutaneous Transluminal Angioplasty (PTA)– Advantages

• short hospital stay• avoidance of general anesthesia and surgical incision• ability to treat surgically inaccessible sites

– PTA and stenting as most effective means of treating restenosis after CEA

– preliminary results of controlled trials:comparable procedural risks compared to CEA



1. CEA is indicated in symptomatic patients with stenosis of 70 - 90%. This is valid only for centres with a perioperative complication rate (all strokes and death) < 6% (Level I)



2. CEA may be indicated in some patients with stenosis of 50 - 59% without a severe neurologic deficit. This is valid only for centres with a perioperative complication rate of < 6%. Males with recent hemispheric symptoms are the subgroup of patients most likely to benefit from surgery (Level I)



3. CEA is not recommended for symptomatic patients with stenosis < 50% (Level I)

4. CEA should not be performed in centres not exhibiting equally low complication rates like NASCET or ECST.



5. CEA may be indicated for some patients with stenosis between 60 and 99%. Only patients with a low surgical risk (<3%) and a life expectancy of at least 5 years are likely to benefit from surgery (Level II)

Primary Prevention


6. Surgery for asymptomatic carotid stenosis is not generally recommended (Level II).

7. It may be recommended in individual patients if the surgical risk is low


• EUSI-recommendations 8. Carotid PTA with or without stenting may be

performed in patients with contra-indications to CEA (Level IV)9. Carotid PTA with or without stenting may be

indicated in patients with stenosis at surgically inaccessible sites (Level IV)

10. Carotid PTA and stenting may be indicated in patients with re-stenosis after initial CEA

(Level IV)

Education

Eusi Stroke