- SYMPOSIUM
RECOMMENDATIONS FOR
STROKE MANAGEMENT
European Federation of
Neurological Societies
EFNS Copenhagn 2000
RECOMMENDATIONS FOR
STROKE MANAGEMENT
• Part 1: Organizing Modern Stroke Care
Tom Skyhoj Olsen, Copenhagn (DEN)
• Part 2: Risk Factors and Primary Prevention
Julien Bogousslavsky, Lausanne (SUI)
• Part 3: Acute Stroke Care - General Therapy
Markku Kaste, Helsinki (FIN)
• Part 4: Acute Stroke Care - Specific Therapy
Werner Hacke, Heidelberg (GER)
• Part 5: Rehabilitation and Secondary Prevention
Jean-Marc Orgogozo, Bordeaux (FRA)
RECOMMENDATIONS FOR
STROKE MANAGEMENT
• Part 1: Organizing Modern Stroke Care
Tom Skyhoj Olsen, Copenhagn (DEN)
RECOMMENDATIONS FOR
STROKE MANAGEMENT
• Part 2: Risk Factors and Primary Prevention
Julien Bogousslavsky, Lausanne (SUI)
RECOMMENDATIONS FOR
STROKE MANAGEMENT
• Part 3: Acute Stroke Care - General Therapy
Markku Kaste, Helsinki (FIN)
RECOMMENDATIONS FOR
STROKE MANAGEMENT
• Part 4: Acute Stroke Care - Specific Therapy
Werner Hacke, Heidelberg (GER)
RECOMMENDATIONS FOR
STROKE MANAGEMENT
• Part 5: Rehabilitation and Secondary Prevention
Jean-Marc Orgogozo, Bordeaux (FRA)
Definitions of Levels of Evidence
modified from Adams et al. 1994
• Level I:
Sources:
Highest Level of Evidence
a) Primary endpoint of double blind RCT with adequate sample size
b) Meta-analysis of qualitatively outstanding RCTs
• Level II:
Sources:
Intermediate Level of Evidence
a) Randomised not blinded trials
b) Small randomised trials
c) Predefined secondary endpoints of large RCTs
• Level III:
Sources:
Lower Level of Evidence
a) Prospective case series with concurrent or historical control
b) Post hoc analyses of large RCTs
• Level IV:
Sources:
Undetermined Level of Evidence
a) Small uncontrolled case series
b) General agreement despite lack of evidence
Acute Stroke CareEmergency Diagnostic Tests
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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)
Emergency Diagnostic Tests
• 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
Emergency Diagnostic Tests
• 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
Emergency Diagnostic Tests
• 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)
Emergency Diagnostic Tests
• Laboratory tests
– hematology
– clotting parameters
– electrolytes
– renal and hepatic chemistry
– cardiac enzymes
– basic parameters of infection
Emergency Diagnostic Tests
• 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
Emergency Diagnostic Tests
• EUSI Recommendations
3. Cardiac and Neurological ultrasound should be
readily available (Level IV)
Acute Stroke CareGeneral 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:
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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
• EUSI Recommendations
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
• EUSI Recommendations
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 CareSpecific 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
Thrombolytic Therapy
• 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?
Thrombolytic Therapy
• 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
Thrombolytic Therapy
• 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
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Head positioning <30°
Pain relief and sedation
Normothermia
Osmotic agents
– Glycerol
– Mannitol
– Hypertonic saline
• Barbiturates, hyperventilation and THAM-buffer
Elevated Intracranial Pressure and
Brain Edema Treatment
• 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
Elevated Intracranial Pressure and
Brain Edema Treatment
• 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
• EUSI Recommendations
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
• EUSI Recommendations
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:
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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
• EUSI-recommendations
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
• EUSI-recommendations
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
Secondary Prevention
• Antithrombotic drugs
– Dipyridamole + aspirin:
• ESPS II: risk reduction of stroke with a combination is
significantly higher (37%) than with aspirin alone
Secondary Prevention
• Antithrombotic drugs
– Clopidogrel
• CAPRIE: Clopidogrel is slightly but significantly more
effective than medium-dose aspirin
Secondary Prevention
• EUSI-recommendations
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)
Secondary Prevention
• EUSI-recommendations
3. Clopidogrel is slightly more effective than
aspirin (Level I). It may be prescribed as firstchoice or when aspirin is not tolerated or
efficacious, and in special indications, such as
in high-risk patients (Level III)
Secondary Prevention
• EUSI-recommendations
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 sideeffects (neutropenia and rash) appear at the
beginning of treatment
Secondary Prevention
• EUSI-recommendations
5. Patients who do not tolerate both ASA or
clopidogrel may be treated with dipyridamol ret
2x200 mg daily (Level I)
Secondary Prevention
• 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
Secondary Prevention
• EUSI-recommendation
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)
Secondary Prevention
• EUSI-recommendation
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)
Secondary Prevention
• 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
Secondary Prevention
• 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
Secondary Prevention
• EUSI-recommendations
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)
Secondary Prevention
• EUSI-recommendations
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)
Secondary Prevention
• EUSI-recommendations
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.
Secondary Prevention
• EUSI-recommendations
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
• EUSI-recommendations
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
Secondary Prevention
• 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)