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The Management of Acute Stroke: Selected Topics

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The Management of Acute Stroke: Selected Topics L. Jay Turkewitz M.D., F.A.A.N. Types of Stroke Ischemia with Bleeding 10-15% Amyloid Angiopathy LOBAR Hypertensive ... – PowerPoint PPT presentation

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Title: The Management of Acute Stroke: Selected Topics


1
The Management of Acute Stroke Selected Topics
  • L. Jay Turkewitz M.D., F.A.A.N.

2
STROKE DEFINITION
  • THE SUDDEN ONSET OF FOCAL NEUROLOGIC DYSFUNCTION
  • SPEECH ISSUES APHASIA OR DYSARTHRIA
  • HEMIPARESIS
  • HEMI SENSORY ISSUES
  • VISUAL LOSS
  • ATAXIA

3
Types of Stroke
85 Ischemic
15 Primary Bleeds
4
Ischemia with Bleeding 10-15
5
Amyloid Angiopathy
  • LOBAR

6
Hypertensive BleedBASAL GANGLIA, PONS, CEREBELLUM
7
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8
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9
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10
In addition to thrombotic occlusion at the site
of cerebral artery atherosclerosis, ischemic
infarction can be produced by emboli arising from
proximally situated atheromatus lesions to
vessels located more distal in the arterial tree.
10
11
Ischemic Strokes
  • Large Vessel Occlusion of the Major Vessels of
    the Neck Outside the Cranial Vault i.e. Carotid
    or Vertebral Occlusion
  • Large or Medium Sized Vessels in the Cranial
    Vault i.e. Middle Cerebral or Basilar occlusion
  • Embolic material breaking away from the heart and
    occluding a vessel down stream so called
    cardiogenic embolus
  • Embolic material breaking away from carotid or
    basilar atheromatous disease in the neck or
    within the cranium and blocking a vessel down
    stream so called artery to artery embolus
  • Small Vessel Occlusions of penetrating vessels
    which take off at right angles so called Lacunar
    Strokes

12
Many Causes of Stroke
13
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14
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15
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16
16
17
Lacunar Strokes
  • Small Penentrating Blood Vessels
  • Pure Motor Stroke
  • Pure Sensory Stroke
  • Ataxia-Hemiparesis
  • Clumsy Hand Dysarthria
  • Excellent prognosis for recovery

18
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19
Stroke Mimics
  • Hypoglycemia
  • Hyperglycemia
  • Seizure
  • Subdural Hematoma

20
Stroke Differential Diagnosis
21
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

Guidelines Ischaemic Stroke 2008
22
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23
DWI Images
  • Acute

24
STROKE
  • MRI

T2
DWI
ADC
25
Perfusion MRI Weighted Image
26
Perfusion Diffusion Mismatch The HOLY GRAIL
  • Acute

27
Emergency Diagnostic Tests
  • 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 identify
    irreversible ischaemic brain injury and to define
    critically impaired blood flow2
  • There is no clear evidence that patients with
    particular perfusion patterns are more or less
    likely to benefit from thrombolysis3

1 Jansen O et al. Lancet (1999) 3532036-2037 2
Kane I et al. Stroke (2007) 383158-3164 3
Albers GW et al. Ann Neurol (2006) 60508-517
28
TPA 3-4.5 Hours
  • ECASS 3 CRUCIAL EFFICACY NOT CLEAR SAFETY IS
  • Excludes anyone on Coumadin even if INR is normal
  • Excludes anyone over 80
  • Excludes NIH Stroke Scale Score over 25
  • Excludes patients with HTN and DM
  • Does not compare to other therapies i.e. mixed
    IV/IA or IA TPA

29
Blood Pressure Management
  • Do NOT Treat BP in Ischemic Stroke unless it is
    over 220/120 or the patient is having an MI,
    Dissection or Acute Glomerulonephritis
  • Stop ALL HOME BP Meds, Trandelenberg, Raise BP???
  • The key is the shift of the auto-regulatory curve
    to the right in hypertensives and the need to
    maintain perfusion
  • Small Changes IN Local Perfusion NOT represented
    by lowering of BP may cause deterioration or
    fluctuation

30
PFO A LONG STORY
  • Percutaneous Device Closure of Patent Foramen
    Ovale for Secondary Stroke Prevention
  • A Call for Completion of Randomized Clinical
    Trials A Science Advisory From the American Heart
    Association/American Stroke Association and the
    American College of Cardiology Foundation The
    American Academy of Neurology affirms the value
    of this science advisory
  • AJC ARTICLE
  • Size
  • ASD
  • ASA
  • ???Anti-Platelets vs Anti-Coagulation

31
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 an
    increase in both incidence and prevalence
  • Stroke is also the second most common cause of
    dementia, the most frequent cause of epilepsy in
    the elderly, and a frequent cause of depression2,3

1 Lopez AD et al. Lancet (2006) 3671747-1757 2
Rothwell PM et al. Lancet (2005) 3661773-1783 3
O'Brien JT et al. Lancet Neurol (2003) 289-98
32
Stroke as an Emergency
  • Background
  • Stroke is a medical and occasionally a surgical
    emergency
  • The majority of ischaemic stroke patients do not
    reach the hospital quickly enough
  • The delay between stroke onset and hospital
    admission is
  • reduced if the Emergency Medical Systems (EMS)
    are used
  • increased if doctors outside the hospital are
    consulted first

33
Stroke as an Emergency
  • Emergency care in acute stroke depends on a
    four-step chain
  • Rapid recognition of, and reaction to, stroke
    signs and symptoms
  • Immediate EMS contact and priority EMS dispatch
  • Priority transport with notification of the
    receiving hospital
  • Immediate emergency room triage, clinical,
    laboratory and imaging evaluation, accurate
    diagnosis, and administration of appropriate
    treatments at the receiving hospital.

34
Stroke as an Emergency
  • Delays during acute stroke management have been
    identified at three different levels1
  • at the population level, due to failure to
    recognize the symptoms of stroke and contact
    emergency services
  • at the level of the emergency services and
    emergency physicians, due to a failure to
    prioritize transport of stroke patients
  • at the hospital level, due to delays in
    neuroimaging and inefficient in-hospital care

1Kwan J et al. Age Ageing (2004) 33116-121
35
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36
Education
  • Recommendations
  • Educational programmes to increase awareness of
    stroke at the population level are recommended
    (Class II,Level B)
  • Educational programmes to increase stroke
    awareness among professionals (paramedics,
    emergency physicians) are recommended (Class II,
    Level B)

37
Referral
  • Recommendations (1/2)
  • Immediate EMS contact and priority EMS dispatch
    are recommended (Class II, Level B)
  • Priority transport with advance notification of
    the receiving hospital is recommended (Class III,
    Level B)
  • Suspected stroke victims should be transported
    without delay to the nearest medical centre with
    a stroke unit that can provide ultra-early
    treatment (Class III, Level B)
  • Patients with suspected TIA should be referred
    without delay to a TIA clinic or a stroke unit
    (Class III, Level B)

38
Referral
  • Recommendations (2/2)
  • Dispatchers and ambulance personnel should be
    trained to recognise stroke using simple
    instruments such as the Face-Arm-Speech-Test
    (Class IV, GCP)
  • Immediate emergency room triage, clinical,
    laboratory and imaging evaluation, accurate
    diagnosis, therapeutic decision and
    administration of appropriate treatments are
    recommended (Class III, Level B)
  • In remote or rural areas helicopter transfer and
    telemedicine should be considered to improve
    access to treatment (Class III, Level C)

39
Emergency Management
  • The time window for treatment of patients with
    acute stroke is narrow
  • Acute emergency management of stroke requires
    parallel processes operating at different levels
    of patient management
  • Acute assessment of neurological and vital
    functions parallels the treatment of acutely
    life-threatening conditions
  • Time is the most important factor

40
Emergency Management
  • The initial examination should include
  • Observation of breathing and pulmonary function
    and concomitant heart disease
  • Assessment of blood pressure and heart rate
  • Determination of arterial oxygen saturation
  • Blood samples for clinical chemistry, coagulation
    and haematology studies
  • Observation of early signs of dysphagia
  • Targeted neurological examination
  • Careful medical history focussing on risk factors
    for arteriosclerosis and cardiac disease

41
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

42
Emergency Management
  • Recommendations
  • Organization of pre-hospital and in-hospital
    pathways and systems for acute stroke patients is
    recommended (Class III, Level C)
  • All patients should receive brain imaging, ECG,
    and laboratory tests. Additional diagnostic
    examinations are necessary in selected patients
    (Class IV, GCP)

43
Stroke Services and Stroke Units
  • Recommendations
  • All stroke patients should be treated in a stroke
    unit(Class I, Level A)
  • Healthcare systems must ensure that acute stroke
    patients can access high technology medical and
    surgical stroke care when required (Class III,
    Level B)
  • The development of clinical networks, including
    telemedicine, is recommended to expand the access
    to high technology specialist stroke care (Class
    II, Level B)

44
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

45
Emergency Diagnostic Tests
  • 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
    stroke onset1
  • Helps to identify other neurological diseases
    (e.g. neoplasms)
  • Most cost-effective strategy for imaging acute
    stroke patients2

1 von Kummer R et al. Radiology (2001)
21995-100 2 Wardlaw J et al. Stroke (2004)
352477-2483
46
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47
DWI Images
  • Acute

48
Emergency Diagnostic Tests
  • 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

Guidelines Ischaemic Stroke 2008
1 Ay H et al. Cerebrovasc Dis (2002) 14177-186
49
Emergency Diagnostic Tests
  • 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 identify
    irreversible ischaemic brain injury and to define
    critically impaired blood flow2
  • There is no clear evidence that patients with
    particular perfusion patterns are more or less
    likely to benefit from thrombolysis3

1 Jansen O et al. Lancet (1999) 3532036-2037 2
Kane I et al. Stroke (2007) 383158-3164 3
Albers GW et al. Ann Neurol (2006) 60508-517
50
Emergency Diagnostic Tests
  • 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 and
    MRA can produce excellent results that are equal
    to Digital subtraction angiography (DSA)2

1 Allendörfer J et al. Lancet Neurology (2005)
5835-840 2 Nederkoorn P et al. Stroke (2003)
341324-1332
51
Emergency Diagnostic Tests
  • 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 provides
    better stroke prediction than clinical risk
    scores3

1 Rothwell P et al. Lancet Neurol (2005)
5323-331 2 Coutts S et al. Ann Neurol (2005)
57848-854 3 Redgrave J et al. Stroke (2007)
381482-1488
52
Emergency Diagnostic Tests
  • Electrocardiogram (ECG)
  • Cardiac abnormalities are common in acute stroke
    patients1
  • Arrhythmias may induce stroke, stroke may cause
    arrhythmias
  • Holter monitoring is superior to routine ECG for
    the detection of atrial fibrillation (AF)2
  • It is unclear whether continuous ECG recording at
    the bedside is equivalent to Holter monitoring
    for the detection of AF

1 Christensen H et al. Neurol Sci (2005) 23499
103 2 Gunalp M et al. Adv Ther (2006) 23854-60
53
Emergency Diagnostic Tests
  • 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 source of embolism, suspected aortic
    disease, suspected paradoxical embolism
  • Transoesophageal echocardiography (TOE) might be
    superior to transthoracic echocardiography (TTE)
    for the detection of potential cardiac sources of
    embolism2

1 Lerakis S et al. Am J Med Sci (2005)
329310-6 2 de Bruijn SF et al. Stroke (2006)
372531-4
54
Emergency Diagnostic Tests
  • Laboratory tests
  • Haematology (RBC, WBC, platelet count)
  • Basic clotting parameters
  • Electrolytes
  • Renal and hepatic chemistry
  • Blood Glucose
  • CRP, sedimentation rate
  • RPR, ANA, Rheumatoid factor
  • Fasting Lipids
  • Homocysteine

55
Hpercoag Work-Up
  • Antiphospholipid Antibodies (Anti-Cardioppin
    Antibodies and Lupus Anti-Coagulant-PTT proxy)
  • Factor V Leiden
  • Anti Thrombin Three Activity
  • Protein C
  • Protein S
  • Prothrombin Gene Mutation

56
Diagnostic Imaging
  • Recommendations
  • In patients with suspected TIA or stroke, urgent
    cranial CT (Class I), or alternatively MRI (Class
    II), is recommended (Level A)
  • If MRI is used, the inclusion of diffusion
    weighted imaging (DWI) and T2-weighted gradient
    echo sequences is recommended (Class II, Level A)
  • In patients with TIA, minor stroke, or early
    spontaneous recovery immediate diagnostic
    work-up, including urgent vascular imaging
    (ultrasound, CT-angiography, or MR angiography)
    is recommended (Class I, Level A)

57
Other Diagnostics
  • Recommendations (1/2)
  • In patients with acute stroke and TIA, early
    evaluation of physiological parameters, routine
    blood tests, and electrocardiography (ECG) is
    recommended (Class I, Level A)
  • All acute stroke and TIA patients should have a
    12-channel ECG. Continuous ECG recording is
    recommended for ischaemic stroke and TIA patients
    (Class I, Level A)

58
Other Diagnostics
  • Recommendations (2/2)
  • For stroke and TIA patients seen after the acute
    phase, 24-hour Holter ECG monitoring should be
    performed when arrhythmias are suspected and no
    other causes of stroke are found (Class I, Level
    A)
  • For all stroke and TIA patients, a sequence of
    blood tests is recommended
  • Echocardiography is recommended in selected
    patients (Class III, Level B)

59
Primary Prevention
  • Content
  • Management of vascular risk factors
  • Antithrombotic therapy
  • Carotid surgery and angioplasty

60
Vascular Risk Factors
  • Conditions and lifestyle characteristics
    identified as a risk factors for stroke
  • High blood pressure High Cholesterol
  • Atrial fibrillation Hyper-homocysteinaemia
  • Diabetes mellitus Smoking
  • Carotid artery disease Heavy alcohol use
  • Myocardial infarction Physical inactivity
  • Obesity

61
High blood pressure (BP)
  • Background
  • High blood pressure (gt120/80mmHg) is the most
    important and prevalent modifiable risk factor
    for stroke
  • Significant reduction of stroke incidence with a
    decrease in BP1
  • No class of antihypertensive is clearly superior
  • LIFE lorsatan is superior to atenolol2
  • ALLHAT chlorthalidone is more effective than
    amlodipine and lisinopril3

1 Neal B et al. Lancet (2000) 3561955-64 2
Dahlof B et al. Lancet (2002) 359995-1003. 3
Mancia G et al. Eur Heart J (2007) 281462-536
62
Diabetes mellitus
  • Background
  • Independent risk factor for ischaemic stroke
  • Improving glucose control may not reduce stroke1
  • BP in patients with diabetes should be
    lt130/80mmHg2
  • Statin treatment reduces the risk of major
    vascular events, including stroke3
  • Elevated blood glucose in the early phase of
    stroke is associated with death and poor recovery

1 Turner RC et al. JAMA (1999) 2812005-12 2
Mancia GJ Hypertens Suppl (2007) 25S7-12 3
Sever PS et al. Diabetes Care (2005) 281151-7
63
High Cholesterol
  • Background
  • Statin treatment reduces the incidence of stroke
    from 3.4 to 2.71
  • 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 lt150 mg/dl (3.9 mmol/l)

1 Amarenco P et al. Stroke (2004)
352902-2909 2 HPS Group Lancet (2002) 3607-22.
64
Cigarette Smoking
  • 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
    an increased stroke risk2
  • 50 risk reduction by 2 years after stopping
    smoking3

1 Shinton R et al. BMJ (1989) 298789-94. 2
Qureshi A et al. Stroke (2005) 3674-76 3
Colditz GA et al. N Engl J Med (1988) 318937-41.
65
Alcohol Consumption
  • Background
  • Increased risk for both ischaemic (RR 1.69) and
    haemorrhagic stroke (RR 2.18) with heavy alcohol
    consumption (gt60g/day)1
  • BP elevation might be a reasonable explanation3
  • Light alcohol consumption (lt12g/day) associated
    with reduced ischaemic (RR 0.80) and haemorrhagic
    stroke1
  • Red wine consumption carries the lowest risk2

1 Reynolds K et al. JAMA (2003) 289579-88 2
Mukamal K et al. Ann Intern Med (2005)
14211-19 3 Bazzano LA et al. Ann Neurol (2007)
66
Physical Activity
  • Background
  • Regular exercise (at least 3x30min/week) is
    associated with a decreased risk of stroke
  • Physically active individuals have a lower risk
    of stroke or death than those with low activity
    (RR 0.73)1
  • This is mediated, in part, through beneficial
    effects on body weight, blood pressure, serum
    cholesterol, and glucose tolerance2

1 Lee C et al. Stroke (2003) 342475-2481 2
Deplanque D et al. Neurology (2006)
671403-1410)
67
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 men but not women2
  • A randomized trial in women found no effect of
    dietary interventions to reduce the incidence of
    stroke3
  • Tocopherol and beta carotene supplementation do
    not reduce the risk of stroke. Vitamin E might
    increase mortality when used at high-dose (400
    IU/d)

1 Kurth T et al. Circulation (2005)
1111992-1998 2 Hu G et al. Arch Intern Med
(2007) 1671420-1427 3 Howard B et al. JAMA
(2006) 295655-666
68
Hormone Replacement Therapy
  • Background
  • Stroke rates rise rapidly in women after the
    menopause
  • Hormone replacement therapy in postmenopausal
    women is associated with an 44 increased risk of
    stroke1

1 Gabriel S et al. Cochrane Review (2005)
CD002229
69
Risk Factor Management
  • Recommendations (1/4)
  • Blood pressure should be checked regularly. High
    blood pressure should be managed with lifestyle
    modification and individualized pharmacological
    therapy (Class I, Level A) aiming at normal
    levels of 120/80 mmHg (Class IV, GCP)

70
Risk Factor Management
  • Recommendations (2/4)
  • Blood glucose should be checked regularly.
    Diabetes should be managed with lifestyle
    modification and individualized pharmacological
    therapy (Class IV, Level C).
  • In diabetic patients, high blood pressure should
    be managed intensively (Class I, Level A) aiming
    for levels below 130/80 mmHg (Class IV, Level C).
    Where possible, treatment should include an
    angiotensin converting enzyme inhibitor or
    angiotensin receptor antagonist (Class I, Level A)

71
Risk Factor Management
  • Recommendations (3/4)
  • Blood cholesterol should be checked regularly.
    High blood cholesterol (e.g. LDLgt150mg/dl
    3,9mMol/l) should be managed with lifestyle
    modification (Class IV, Level C) and a statin
    (Class I, Level A)
  • Cigarette smoking should be discouraged (Class
    III, Level B)
  • Heavy use of alcohol should be discouraged (Class
    III, Level B)
  • Regular physical activity is recommended (Class
    III, Level B)

72
Risk Factor Management
  • 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 are
    recommended to take a weight-reducing diet (Class
    III, Level B)
  • Antioxidant vitamin supplements are not
    recommended (Class I, Level A)
  • Hormone replacement therapy is not recommended
    for the primary prevention of stroke (Class I,
    Level A)

73
Antithrombotic Therapy
  • 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 95CI 0.63-0.93) 2
  • Aspirin reduces MI in patients with asymptomatic
    carotid artery disease3

1 Bartolucci A et al. Am J Cardiol (2006)
98746-750 2 Berger J et al. JAMA (2006)
295306-313 3 Hobson R, 2nd et al. J Vasc Surg
(1993) 17257-263
74
Atrial fibrillation (AF)
  • 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 at reducing stroke (RR 0.36 95CI
    0.26-0.51)1
  • Combination of aspirin and clopidogrel is less
    effective than warfarin and has a similar
    bleeding rate2

1 Hart RG et al. Ann Intern Med (2007)
146857-867 2 Connolly S et al. Lancet (2006)
3671903-1912
75
Atrial fibrillation (AF)
  • Background
  • Anticoagulation with an INR below 2.0 is not
    effective
  • Increased risk for bleeding complications with an
    INR gt 3.5
  • Patients lt65 years of age with lone AF (without
    other risk factors) are at low risk, whereas
    patients older than 65 years are at a higher risk
    for embolic stroke
  • Anticoagulation can be safe and effective in
    older individuals1, 2

1 Rash A et al. Age Ageing (2007) 36151-156 2
Mant J et al. Lancet (2007) 370493-503
76
Antithrombotic Therapy
  • 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 the
    primary prevention of myocardial infarction
    however, it does not reduce the risk of ischaemic
    stroke (Class I, Level A)

77
Antithrombotic Therapy
  • Recommendations (3/4)
  • Unless contraindicated, an oral anticoagulant
    (INR 2.03.0) is recommended for patients with
    non-valvular AF who are aged gt75, or who are
    younger but have risk factors such as high blood
    pressure, left ventricular dysfunction, or
    diabetes mellitus (Class I, Level A)

78
Antithrombotic Therapy
  • 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
    heart valves should receive long-term
    anticoagulation with a target INR based on the
    prosthesis type, but not less than INR 23 (Class
    II, Level B)
  • Low dose aspirin is recommended for patients with
    asymptomatic internal carotid artery (ICA)
    stenosis gt50 to reduce their risk of vascular
    events (Class II, Level B)

79
Asymptomatic carotid artery (ICA) stenosis
  • Background1,2
  • Carotid endarterectomy (CEA) is still a matter of
    controversy in asymptomatic individuals
  • RRR for stenosis gt60NASCET is 38-53
  • ARR is 5.9-12.6
  • NNT to avoid one stroke/year is 63-166
  • The combined surgical risk must not exceed 3

1 ACAS JAMA (1995) 2731421-8. 2 ACST Lancet
(2004) 3631491-1502
80
Asymptomatic carotid artery (ICA) stenosis
  • 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 do not benefit from endarterectomy3
  • Women have lower benefit from CEA than men3
  • Aspirin reduces stroke risk during and after CEA4

1 Chambers BR et al. Cochrane Review (2005) 2
ECST Group Lancet (1995) 345209-12 3 Baker WH
et al. Stroke (2000) 312330-4 4 Engelter S et
al. Cochrane Reviews (2003)
81
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
    not recommended for patients with asymptomatic
    carotid stenosis (Class IV, GCP)
  • Patients should take aspirin before and after CEA
    (Class I, Level A)

82
Secondary Prevention
  • Content
  • Management of vascular risk factors
  • Antithrombotic therapy
  • Surgery and angioplasty

83
Blood pressure control
  • Background
  • Antihypertensive drugs reduce stroke recurrence
    risk after stroke or TIA (RR 0.76 95CI
    0.63-0.92)1
  • Target BP level and reduction should be
    individualized
  • The reduction in stroke occurs regardless of
    baseline BP and type of stroke2

1 Rashid P et al. Stroke (2003) 342741-8 2
PROGRESS group Lancet (2001) 3581033-41
84
Diabetes Mellitus
  • Background
  • In people with type 2 diabetes with previous
    stroke pioglitazone reduces fatal or nonfatal
    stroke (HR 0.53 95CI 0.34-0.85 P0.0085)1
  • In addition there is a trend to reduce the
    combined end point of death and major vascular
    events (HR 0.78 95CI 0.60-1.02 P0.067)1

1 Wilcox R et al. Stroke (2007) 38865-73
85
High Cholesterol
  • Background
  • Atorvastatin (80mg) reduces stroke recurrence by
    161
  • Simvastatin (40mg) reduces risk of vascular
    events in patients with prior stroke, and of
    stroke in patients with other vascular disease
    (RR 0.76)2
  • ARR for statin treatment is low (NNT 112-143 for
    1 year)1
  • Statin withdrawal at the acute stage of stroke
    may be harmful3

1 Amarenco P et al. N Engl J Med (2006)
355549-559 2 Heart Protection Study Lancet
(2002) 3607-22 3 Blanco M et al. Neurology
(2007) 69904-10
86
Vitamins
  • Background
  • Beta carotene increased the risk (RR 1.10) of
    cardiovascular death1
  • Antioxidant supplements may increase mortality2
  • Folate, B12, B6 vitamins given to lower
    homocysteine levels may not reduce stroke
    recurrence and may increase vascular events3

1 Vivekananthan D et al. Lancet (2003)
3612017-2023 2 Bjelakovic G et al. JAMA (2007)
297842-857 3 Bonaa K et al. N Engl J Med
(2006) 3541578-1588
87
Hormone Replacement Therapy
  • Background
  • Oestrogen therapy is not effective in secondary
    prevention after TIA or stroke and may increase
    stroke severity1

1 Viscoli CM et al. N Engl J Med (2001)
3451243-9.
88
Sleep-disordered Breathing
  • Background
  • Sleep-disordered breathing (SDB) is both a risk
    factor and a consequence of stroke
  • More than 50 of stroke patients have SDB, mostly
    in the form of obstructive sleep apnoea (OSA).
  • SDB is linked with poorer long-term outcome and
    increased long-term stroke mortality1
  • Continuous positive airway pressure is the
    treatment of choice for OSA.

1 Bassetti CL Semin Neurol (2005) 2519-32
89
Risk Factor Management
  • 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.
    Diabetes should be managed with lifestyle
    modification and individualized pharmacological
    therapy (Class IV, GCP)
  • In patients with type 2 diabetes who do not need
    insulin, treatment with pioglitazone is
    recommended after stroke (Class III, Level B)

90
Risk Factor Management
  • 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)

91
Risk Factor Management
  • 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
    continuous positive airway pressure breathing
    (Class III, Level GCP)

92
Antithrombotic Therapy
  • Background Aspirin
  • 13 relative risk reduction for stroke after TIA
    or stroke1
  • Most widely studied dosages of aspirin are
    50-150mg
  • The incidence of GI-disturbances with aspirin is
    dose dependent
  • No difference in effectiveness amongst low (lt
    160mg), medium (160 325mg) or high (500 -
    1500mg) dose aspirin

1 Antithrombotic Trialists' Collaboration BMJ
(2002) 32471-86
93
Antithrombotic Therapy
  • Background Dipyridamole plus aspirin
  • Relative risk reduction of vascular death, stroke
    or myocardial infarction with the combination is
    significantly greater (RR 0.82 95CI 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)
1431-13 2 Halkes P et al. Lancet (2006)
3671665-1673 3 Chang YJ et al. Cerebrovasc Dis
(2006) 22258-62
94
Antithrombotic Therapy
  • 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) 3671665-1673
95
Antithrombotic Therapy
  • Background Clopidogrel
  • Clopidogrel is slightly but significantly more
    effective than medium-dose aspirin (RRR 8.7, ARR
    0,5) in preventing vascular events in patients
    with previous stroke, MI or PAD1

1 CAPRIE Steering Committee Lancet (1996)
3481329-1339
96
Antithrombotic Therapy
  • Background Clopidogrel plus aspirin
  • Compared with clopidogrel the combination of
    aspirin and clopidogrel does not reduce the risk
    of ischaemic stroke, myocardial infarction,
    vascular death, or re-hospitalisation1
  • Compared with aspirin alone the combination does
    not reduce the risk of myocardial infarction,
    stroke, or cardiovascular death2
  • Risk of life-threatening or major bleeding is
    increased1,2

1 Diener H et al. Lancet (2004) 364331-337 2
Bhatt D et al. N Engl J Med (2006) 3541706-1717
97
Antithrombotic Therapy
  • Recommendations (1/4)
  • Patients should receive antithrombotic therapy
    (Class I, Level A)
  • Patients not requiring anticoagulation should
    receive antiplatelet therapy (Class I, Level A).
    Where possible, combined aspirin and
    dipyridamole, or clopidogrel alone, should be
    given. Alternatively, aspirin alone, or triflusal
    alone, may be used (Class I, Level A)

98
Antithrombotic Therapy
  • 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 9
    months after the event (Class I, Level A)
  • Patients who have a stroke on antiplatelet
    therapy should be re-evaluated for
    pathophysiology and risk factors (Class IV, GCP)

99
Anticoagulation
  • Background
  • Oral antiocoagulation (target INR 2.0 3.0)
    reduces the risk of recurrent stroke in patients
    with AF1
  • Oral anticoagulation is well established for
    other causes of embolism such as mechanical
    prosthetic valve replacement, rheumatic valvular
    heart disease, ventricular aneurysm and
    cardiomyopathy
  • There is no indication for oral anticoagulation
    in patients with non-cardiac cause of ischaemic
    stroke2

1 EAFT Study Group Lancet (1993)
3421255-1262 2 Mohr JP et al. N Engl J Med
(2001) 3451444-1451
100
Anticoagulation
  • Specific issues
  • In patients with AF and stable coronary disease,
    aspirin should not be added to oral
    anticoagulation1
  • Some retrospective studies suggest that
    anticoagu-lation may be beneficial in aortic
    atheroma2, fusiform basilar artery aneurysms3, or
    arterial dissection4
  • It is unclear if patients with patent foramen
    ovale (PFO) benefit from oral anticoagulation5

1 Flaker GC et al. Am Heart J (2006)
152967-73 2 Dressler FA et al. J Am Coll
Cardiol (1998) 31134-8 3 Echiverri HC et al.
Stroke (1989) 201741-7 4 Engelter ST et al.
Stroke (2007) 382605-11 5 Mas JL et al. N Engl
J Med (2001) 3451740-6
101
Antithrombotic Therapy
  • Recommendations (3/4)
  • Anticoagulation should not be used after
    non-cardio-embolic ischaemic stroke, except in
    some specific situations, such as aortic
    atheromas, fusiform aneurysms of the basilar
    artery, cervical artery dissection, or patent
    foramen ovale in the presence of proven deep vein
    thrombosis (DVT) or atrial septal aneurysm (Class
    IV, GCP)
  • If oral anticoagulation is contraindicated,
    combined low dose aspirin and dipyridamole should
    be given (Class IV, GCP)

102
Antithrombotic Therapy
  • Recommendations (4/4)
  • Oral anticoagulation (INR 2.03.0) is recommended
    after ischaemic stroke associated with AF (Class
    I, Level A). Oral anticoagulation is not
    recommended in patients with co-morbid conditions
    such as falls, poor compliance, uncontrolled
    epilepsy, or gastrointestinal bleeding (Class
    III, Level C). Increasing age alone is not a
    contraindication to oral anticoagulation (Class
    I, Level A)
  • Patients with cardioembolic stroke unrelated to
    AF should receive anticoagulants (INR 2.0-3.0) if
    the risk of recurrence is high (Class III, Level
    C)

103
Carotid Endarterectomy (CEA)
  • Background1,2
  • CEA reduces the risk by 48 of recurrent
    disabling stroke or death in patients with
    70-99NASCET ipsilateral carotid artery stenosis
  • If perioperative complications exceed 6, the
    benefit of CEA will diminish if it approaches
    10, the benefit will vanish entirely
  • There is also some risk reduction in male
    patients with 50 - 69 stenosis of the
    ipsilateral carotid artery, provided that the
    complication rate is below 3

1 NASCET Collaborators NEJM (1991)
325445-453 2 Warlow C Lancet (1991)
3371235-1243
104
Carotid Endarterectomy
  • Specific issues
  • CEA should be performed as soon as possible
    (ideally within 2 weeks) after the last
    cerebrovascular event1,2
  • Elderly patients (gt75 years) without organ
    failure or serious cardiac dysfunction benefit
    from CEA1
  • Women with symptomatic stenosis gt70 should
    undergo CEA. Women with moderate stenosis should
    be treated medically2

1 Rothwell PM et al. Lancet (2004)
363915-924 2 Rothwell PM et al. Stroke (2004)
352855-61
105
Carotid Endarterectomy
  • Effect of time from last symptomatic event to
    randomisation on the 5-year relative risk (RR) of
    ipsilateral ischaemic stroke and any operative
    stroke or death with CEA (pooled data from ECST
    and NASCET1)

1 Rothwell PM et al. Stroke (2004) 352855-61
106
Carotid Endarterectomy
  • 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

107
Carotid Artery Stenting (CAS)
  • Background
  • No randomized trial has demonstrated equivalent
    periprocedural risk for CAS compared to CEA in
    treatment of symptomatic carotid artery stenosis
  • A European study only marginally failed to prove
    the non-inferiority of CAS compared to CEA
  • A French study was stopped prematurely because of
    a 2.5 fold higher risk of any stroke or death
    after CAS2

1 Ringleb PA et al. Lancet (2006)
3681239-1247 2 Mas JL et al. NEJM (2006)
3551660-1671
108
Carotid Artery Stenting
  • Metaanalysis CAS vs. CEA Endpoint any
    periprocedural stroke or death

1 Kastrup A et al. Acta Chir Belg (2007)
107119-28
109
CREST STUDY
  • Landmark NIH Clinical Trial Comparing Two Stroke
    Prevention Procedures Shows Surgery and Stenting
    Equally Safe and Effective
  • Opportunities Exist to Target the Treatment to
    the Patient

110
Intracranial Occlusive Disease
  • Background
  • Extracranial-Intracranial bypass is not
    beneficial in preventing stroke in patients with
    MCA or ICA stenosis or occlusion1
  • No randomized controlled trials have evaluated
    angioplasty, stenting, or both for intracranial
    stenosis
  • Several non-randomized trials have shown
    feasibility and acceptable safety of intracranial
    stenting, but the risk of re-stenosis remains
    high2,3

1 The EC/IC Bypass Grp N Engl J Med (1985)
3131191-200 2 Bose A et al. Stroke (2007)
381531-7 3 SSYLVIA Study investigators Stroke
(2004) 351388-92
111
Surgery and Angioplasty
  • Recommendations (1/4)
  • CEA is recommended for patients with 7099
    stenosis (NASCET criteria) (Class I, Level A).
    CEA should only be performed in centres with a
    perioperative complication rate (all strokes and
    death) of less than 6 (Class I, Level A)
  • CEA should be performed as soon as possible after
    the last ischaemic event, ideally within 2 weeks
    (Class II, Level B)

112
Surgery and Angioplasty
  • Recommendations (2/4)
  • CEA may be indicated for certain patients with
    stenosis of 5069 (NASCET criteria) males with
    very recent hemispheric symptoms are most likely
    to benefit (Class III, Level C). CEA for stenosis
    of 5069 (NASCET criteria) should only be
    performed in centres with a perioperative
    complication rate (all stroke and death) of less
    than 3 (Class I, Level A)
  • CEA is not recommended for patients with stenosis
    of less than 50 (NASCET criteria) (Class I,
    Level A)

113
Surgery and Angioplasty
  • 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 following subgroups of
    patients with severe symptomatic carotid artery
    stenosis those with contra-indications to CEA,
    stenosis at a surgically inaccessible site,
    re-stenosis after earlier CEA, and post-radiation
    stenosis (Class IV, GCP)

114
Surgery and Angioplasty
  • 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
    patients with symptomatic intracranial stenosis
    (Class IV, GPC)

115
General Stroke Treatment
  • Content
  • Monitoring
  • Pulmonary and airway care
  • Fluid balance
  • Blood pressure
  • Glucose metabolism
  • Body temperature

116
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)

117
Pulmonary function
  • Background
  • Adequate oxygenation is important
  • Improve blood oxygenation by administration of gt
    2 l O2
  • Risk for aspiration in patients with side
    positioning
  • Hypoventilation may be caused by pathological
    respiration pattern
  • Risk of airway obstruction (vomiting,
    oropharyngeal muscular hypotonia) mechanical
    airway protection

118
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 passively
    dependent on the mean arterial pressure
  • There are no adequately sized randomised,
    controlled studies guiding BP management

119
Blood pressure
  • Specific issues
  • Elevated BP (e.g. up to 200mmHg systolic or
    110mmHg diastolic) may be tolerated in the acute
    phase of ischaemic stroke without intervention
  • BP may be lowered if this is required by cardiac
    conditions
  • Upper level of systolic BP in patients undergoing
    thrombolytic therapy is 180mmHg
  • Avoid and treat hypotension
  • Avoid drastic reduction in BP

120
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
    moderate hyperglycaemia did not improve outcome1
  • It is common practise to treat hyperglycemia with
    insulin when blood glucose exceeds 180mg/dl2
    (10mmol/l)

1 Gray CS et al. Lancet Neurol (2007)
6397-406 2 Langhorne P et al. Age Ageing
(2002) 31365-71.
121
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 febrile
    infection
  • There are no adequately sized trials guiding
    temperature management after stroke
  • It is common practice treat fever (and its cause)
    when the temperature reaches 37.5C

122
General Stroke Treatment
  • Recommendations (1/4)
  • Intermittent monitoring of neurological status,
    pulse, blood pressure, temperature and oxygen
    saturation is recommended for 72 hours in
    patients with significant persisting neurological
    deficits (Class IV, GCP)
  • Oxygen should be administered if sPO2 falls below
    95 (Class IV, GCP)
  • Regular monitoring of fluid balance and
    electrolytes is recommended in patients with
    severe stroke or swallowing problems (Class IV,
    GCP)

123
General Stroke Treatment
  • 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
    recommended following acute stroke (Class IV,
    GCP)
  • Cautious blood pressure lowering is recommended
    in patients with any of the following extremely
    high blood pressures (gt220/120 mmHg) on repeated
    measurements, or severe cardiac failure, aortic
    dissection, or hyper-tensive encephalopathy
    (Class IV, GCP)

124
General Stroke Treatment
  • 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 stroke should be treated with volume
    expanders (Class IV GCP)
  • Monitoring serum glucose levels is recommended
    (Class IV, GCP)
  • Treatment of serum glucose levels gt180mg/dl
    (gt10mmol/l) with insulin titration is recommended
    (Class IV, GCP)

125
General Stroke Treatment
  • Recommendations (4/4)
  • Severe hypoglycaemia (lt50 mg/dl lt2.8 mmol/l)
    should be treated with intravenous dextrose or
    infusion of 1020 glucose (Class IV, GCP points)
  • The presence of pyrexia (temperature gt37.5C)
    should prompt a search for concurrent infection
    (Class IV, GCP)
  • Treatment of pyrexia (gt37.5C) with paracetamol
    and fanning is recommended (Class III, Level C)
  • Antibiotic prophylaxis is not recommended in
    immunocompetent patients (Class II, Level B)

126
Specific Stroke Treatment
  • Content
  • Thrombolytic therapy
  • Early antithrombotic treatment
  • Treatment of elevated intracranial pressure
  • Prevention and management of complications

127
Thrombolytic Therapy (i.v. rtPA)
  • Background (NINDS1, ECASS I2 II3, ATLANTIS4)
  • Intravenous rtPA (0.9mg/kg, max 90mg) given
    within 3 hours of stroke onset, significantly
    improves outcome in patients with acute ischaemic
    stroke
  • Benefit from the use of i.v. rtPA beyond 3 hours
    is smaller, but may be present up to at least 4.5
    hours
  • Several contraindications

1 NINDS rt-PA Grp New Engl J Med (1995)
3331581-1587 2 Hacke W et al. JAMA (1995)
2741017-1025 3 Hacke W et al. Lancet (1998)
3521245-1251 4 Clark WM et al. Jama (1999)
2822019-26.
128
Thrombolytic Therapy (i.v. rtPA)
  • 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 (NIHSSSgt25), or if the
    CT demonstrates extended early infarcts signs
  • Thrombolytic therapy must be given by an
    experienced stroke physician after the imaging of
    the brain is assessed by physicians experienced
    in reading this imaging study2

1 Hacke W et al. Lancet (2004) 363768-74 2
Wahlgren N et al. Lancet (2007) 369275-82
129
Thrombolytic Therapy (i.v. rtPA)
  • 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) 382275-8
130
Thrombolytic Therapy (i.v. rtPA)
  • Risk and outcome from 6,483 patients of the
    SITS-Most treated with iv-rtPA within a 3 hour
    time window1

1 Wahlgren N et al. Lancet (2007) 369275-82
131
Thrombolytic Therapy (i.v. rtPA)
  • 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 in routine practice3
  • Data regarding the use of intravenous
    desmoteplase administered 3 to 9 hours after
    acute ischaemic stroke in patients selected on
    the basis of perfusion/diffusion mismatch are
    conflicting

1 Köhrmann M et al. Lancet Neurol (2006)
5661-7 2 Chalela J et al. Lancet (2007)
369293-298 3 Kane I et al. JNNP (2007)
78485-490
132
Thrombolytic Therapy (i.a.)
  • 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) 2822003-11
133
Specific Treatment
  • 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-minute infusion, is recommended within 3
    hours of onset of ischaemic stroke (Class I,
    Level A)
  • Intravenous rtPA may be of benefit also for acute
    ischaemic stroke beyond 3 hours after onset
    (Class I, Level B) but is not recommended for
    routine clinical practice. The use of multimodal
    imaging criteria may be useful for patient
    selection (Class III, Level C)

134
Specific Treatment
  • 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 acute cerebral ischaemia
    (Class IV, GCP)
  • Intravenous rtPA may also be administered in
    selected patients over 80 years of age, although
    this is outside the current European labelling
    (Class III, Level C)

135
Specific Treatment
  • 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
    acute basilar occlusion in selected patients
    (Class III, Level B) Intravenous thrombolysis for
    basilar occlusion is an acceptable alternative
    even after 3 hours (Class III, Level B)

136
Antiplatelet therapy
  • Background
  • Aspirin was tested in large RCTs in acute (lt48 h)
    stroke1,2
  • Significant reduction was seen in death and
    dependency (NNT 70) and recurrence of stroke (NNT
    140)
  • A phase 3 trial for the glycoprotein-IIb-IIIa
    antagonist abciximab was stopped prematurely
    because of an increased rate of bleeding3

1 International-Stroke-Trial Lancet (1997)
3491569-1581 2 CAST-Collaborative-Group
Lancet (1997) 3491641-1649 3 Adams HP, Jr. et
al. Stroke (2007)
137
Anticoagulation
  • Unfractionated heparin
  • No formal trial available testing standard i.v.
    heparin
  • IST showed no net benefit for s.c. heparin
    treated patients because of increased risk of
    ICH1
  • Low molecular weight heparin
  • No benefit on stroke outcome for low molecular
    heparin (nadroparin, certoparin, tinzaparin,
    dalteparin)
  • Heparinoid (orgaran)
  • TOAST trial neutral2

1 International-Stroke-Trial Lancet (1997)
3491569-1581 2 TOAST Investigators JAMA (1998)
2791265-72.
138
Neuroprotection
  • No adequately sized trial has yet shown
    significant effect in predefined endpoints for
    any neuroprotective substance
  • A meta-analysis has suggested a mild benefit for
    citocoline1

1 Davalos A et al. Stroke (2002) 332850-7
139
Specific Treatment
  • Recommendations (4/5)
  • Aspirin (160325 mg loading dose) should be given
    within 48 hours after ischaemic s
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