Stroke

1
Stroke These slides were kindly provided
by AstraZeneca
2
Stroke definitions
An injury to the brain caused by

• Interruption of blood flow
  (ischaemic stroke)
• or
• Bleeding into or around the brain
  (haemorrhagic stroke)

3
Transient ischaemic attack (TIA)

• Brief episode in which neurological deficits
  suddenly occur, then disappear can persist up to
  24 hours
• Temporary arterial blockage, with no resultant
  brain damage

4
Stroke - definitions
Stroke
IschaemicOcclusion of a vessel
HaemorrhagicRupture of a vessel
Ischaemia
Clot /occlusion
Carotidartery

• Focal stroke Neurological deficit lasting more
  than 24 hours caused by reduced blood flow that
  ultimately results in infarction
• Transient ischaemic attack (TIA) lt24 hours

5
Ischaemic strokes
Forebrain
Thalamus

• Areas of brain affected
• Forebrain (frontal lobe and thalamus) gt Brainstem
  gt Cerebellum gt Spinal cord
• Lacunar stroke
• Area of infarction has form of lacune or cavity
  (lt15 mm). These are smaller strokes

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Stroke definitions
Stroke
IschaemicOcclusion of a vessel
HaemorrhagicRupture of a vessel
Ischaemia
Clot /occlusion
Rupture producesinjury by distorting,compressing
andtearing thesurrounding braintissue or
byincreasingintracranialpressure
Carotidartery
7
Causes of haemorrhagic strokes
Approximately 50 due to

• Aneurysm rupture (often a subarachnoid
  haemorrhage occurs first)
• AV malformation

Other causes

• Intracerebral haemorrhage
• Rupture of small penetrating arteries with direct
  bleeding into brain or ventricles
• Lobar haemorrhage (small vessels)
• Amyloid angiopathy

8
Stroke definitions
Stroke
IschaemicOcclusion of a vessel
HaemorrhagicRupture of a vessel
Ischaemia
Clot /occlusion
Rupture producesinjury by distorting,compressing
andtearing thesurrounding braintissue or
byincreasingintracranialpressure
Carotidartery

• Stroke leads to the death of brain cells. This
  can result in
• Paralysis
• Speech and sensory problems
• Memory and reasoning deficits

• Coma
• Possibly death

9
Stroke incidence and prevalence
Cause of death
1. Cardiovascular disease 2. Cancer 3. Stroke
531.000 new cases of strokeand 200.000
recurrences ofstroke each year in the US
In 22 European countries with acombined
population of approximately 500 million, almost
one million strokes areestimated to occur each
year
Sorelle R. Circulation 2000102E9047-9 Brainin M
et al. Eur J Neurol 199975-10
10
Stroke high rate of morbidity

• Leading cause of morbidity and long-term
  disability in most industrialised nations

Percent of stroke patients
71
31
20
16
Institutionalised
Walking assistance required
Daily care required
Impaired ability to work
When examined an average of 7 years after
occurrence of stroke
American Heart Association 1996
11
Stroke aetiology

• Ischaemic strokes
• Cerebrovascular disease
• Embolism

85
Ischaemicstrokes
15
Haemorrhagicstrokes

• Haemorrhagic strokes
• Hypertension
• Aneurysms
• Arteriovenous malformations

Cerabral Embolism Task Force. Arch Neurol
19864371-84
12
Stroke aetiology

• Ischaemic strokes
• Cerebrovascular disease
• Embolism

CardiogenicEmboli
85
20
Ischaemicstrokes
80
15
Other
Haemorrhagicstrokes

• Haemorrhagic strokes
• Hypertension
• Aneurysms
• Arteriovenous malformations

Cerabral Embolism Task Force. Arch Neurol
19864371-84
13
Stroke aetiology

• Ischaemic strokes
• Cerebrovascular disease
• Embolism

Mitral stenosis
Prosthetic valves
CardiogenicEmboli
Less common sources
85
20
10
Ischaemicstrokes
10
45
10
80
15
10
Other
Haemorrhagicstrokes
15
Ventricular dysfunction

• Haemorrhagic strokes
• Hypertension
• Aneurysms
• Arteriovenous malformations

Myocardial infarction
Nonvalvular atrial fibrillation
Cerabral Embolism Task Force. Arch Neurol
19864371-84
14
Atrial fibrillation key risk factor for stroke
Ischaemic Stroke
Sources of cardiogenic emboli
80 Other
Less commonsources
Prostheticvalves
10
20CardiogenicEmboli
Nonvalvular atrial fibrillation
10
45
Mitralstenosis
10
10
Ventricular dysfunction
15
Myocardialinfarction
Cerabral Embolism Task Force. Arch Neurol
19864371-84
15
Stroke risk factors
Non-modifiable risk factors
Potentially modifiable risk factors

• Age
• Male gender
• Ethnicity
• Genetic factors

• Cardiac disease
• Hypertension
• Hyperlipidaemia
• Cigarette smoking
• Diabetes mellitus
• Physical inactivity
• Drug abuse

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Well documented modifiable risk factors for stroke

• Prevalence Relative Factor risk Risk
  reduction with treatment
• Hypertension 38- 50 years 20 4.0- 60
  years 30 3.0- 70 years 40 2.0- 80
  years 55 1.4- 90 years 60 1.0 Smoking 25 1.8 50
  within 1 year, baseline after 5 years
• Diabetes 20 1.8-6.0 Reduction of stroke risk in
  hypertensive diabetics with blood pressure
  control. No demonstrated benefit in stroke
  reduction with tight glycemic
  controlAsymptomatic 2-8 2.0 50
• carotid stenosis
• Hyperlipidemia 20-30 with statins in patients
  with known coronary disease- adults lt35
  years 8-9 1.8
• men 55 years 25 2.6
• women 65 years 40
• Atrial fibrillation (nonvalvular) 68 warfarin
  21 aspirin - 50-59 years 0.5 4.0 - 60-69
  years 1.8 2.6 - 70-79 years 4.8 3.3- 80-89
  years 8.8 4.5

Goldstein LB et al. Circulation 2001103163-82
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Ischaemic stroke
18
Cerebral ischaemia
19
Cerebral ischaemia
Ischaemia

• Severity of the insult determines
• Transient ischaemic attack (TIA)
• Selective necrosis
• Cerebral infarction (pan-necrosis)

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Cerebral ischaemia
Duration of ischaemia
21
Cerebral ischaemia
Duration of ischaemia

• Cerebral ischaemia can produce irreversible
  injury to highly vulnerable neurons in 5 minutes

22
Cerebral ischaemia
Duration of ischaemia

• Cerebral ischaemia can produce irreversible
  injury to highly vulnerable neurons in 5 minutes
• If cerebral ischaemia persists for gt6 hours,
  infarction of part or all of the involved
  vascular territory is completed

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Cerebral ischaemia
Duration of ischaemia

• Cerebral ischaemia can produce irreversible
  injury to highly vulnerable neurons in 5 minutes
• If cerebral ischaemia persists for gt6 hours,
  infarction of part or all of the involved
  vascular territory is completed
• Clinical evidence depends on the location of
  stroke

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Degree of neurologic injury
Neurologic injury
100
NR
75
50
ET50
25
CR
0
0
100
200
300
400
500
Duration of ischaemia (min)
Zivin JA. Neurology 199850599603
25
Intracranial haemorrhage
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Intracranial haemorrhage
Anteriorcerebral artery (ACA)
Middlecerebral artery (MCA)
Basilarartery
Vertebral arteries
Posterior cerebral artery
27
Intracranial haemorrhage
Anteriorcerebral artery (ACA)
Middlecerebral artery (MCA)
Basilarartery
Vertebral arteries
Posterior cerebral artery
28
Intracranial haemorrhage
Anteriorcerebral artery (ACA)
Middlecerebral artery (MCA)
Basilarartery
Vertebral arteries
Posterior cerebral artery
29
Intracranial haemorrhage
Anteriorcerebral artery (ACA)
Middlecerebral artery (MCA)
Basilarartery
Blood in subarachnoid space
Vertebral arteries
Posterior cerebral artery
30
Intracranial haemorrhage
Circle of Willis
Anteriorcerebral artery (ACA)
Middlecerebral artery (MCA)
Basilarartery
Blood in subarachnoid space
Vertebral arteries
Posterior cerebral artery
31
Intracranial haemorrhage
Circle of Willis
Anteriorcerebral artery (ACA)
Middlecerebral artery (MCA)
Basilarartery
Blood in subarachnoid space
Vertebral arteries
Posterior cerebral artery

• Intraparenchymal haemorrhage may be relatively
  benign
• Bleeding into the region of previous infarction
  causes no additional functional loss
• At the site of rupture, bleeding into the brain
  may cause traumatic injury to the exposed tissue,
  and blood or its breakdown products in the
  parenchyma damages brain tissues

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Stroke cerebrovascular accident (CVA)
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Functional impact of stroke
Transient
11
Fatal
31
Non-disabling
17
11
Moderately disabling
28
Severe neurological deficit
109 episodes in 100 patients
Fisher CM. Geriatrics 19793459-61
34
AF-related stroke

• In patients with AF, there is a greater risk of
  stroke being fatal or leaving the patient with a
  long-term disability compared with patients
  without AF, resulting in
• increased duration of hospital stay and need for
  long-term institutional care
• greater family, social and financial burden of
  stroke

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Permanent neurological deficits of stroke

• Weakness or paralysis
• Loss of sensation
• Problems with vision
• Difficulty in speech comprehension / talking
• Difficulty with organization or perception
• Clumsiness or lack of balance

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What stroke can mean for patients

• Sudden numbness or weakness of the face, arm or
  leg, especially on one side of the body
• Sudden confusion, trouble speaking or
  understanding speech
• Sudden trouble seeing, on one or both eyes
• Sudden trouble walking, dizziness, loss of
  balance or co-ordination
• Sudden severe headache with no known cause

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What stroke can mean for family and carers

• Recovery from stroke is seldom complete and it is
  estimated that 40 of patients living at home
  after stroke need help in daily living.
•  
• Four out of five patients survive a stroke, ten
  years later the patient has only a 50 chance of
  still being alive.

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Stroke diagnosis
Stroke

• Common symptoms
• Weakness and sensory loss down one side of the
  body
• Disturbances of consciousness and confusion
• Impariment of speech, vision and co-ordination of
  movement

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Computed tomography (CT) and magnetic resonance
imaging (MRI)
CT scan
MRI scan
40
Computed tomography (CT) and magnetic resonance
imaging (MRI)
CT scan
MRI scan

• Images taken in two-dimensional slices
• Can be reconstructed into three-dimensional images

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Computed tomography (CT)

• Principle differential absorption of x-ray beams
  by different tissues
• Less time
• Less expensive
• More available in emergency rooms
• Not reliable if done too early

CT scan

• Easily detects
• Blood products (haemorrhages larger than 1 cm
  diameter)
• Hydrocephalus
• Brain oedema
• Herniation

42
Magnetic resonance imaging (MRI)
Cerebral infarction

• High-resolution neural imaging technique
• Principle protons in body water molecules are
  magnetised and then returned to equilibrium
  states in two relaxation times, T1 and T2
• Different parts of the brain have different
  signal intensities on T1- or T2-weighted images

MRI scan
43
Diffusion-weighted imaging (DWI) MRI

• Best way to image acute stroke
• Principle rapid-pulse sequence with average
  total time lt2 minutes
• Ischaemia can be visualised as early as within 30
  minutes of stroke
• Relies on reduction of random diffusion (Brownian
  motion) of water after acute stroke

MRI scan
44
Diffusion-weighted imaging (DWI) MRI

• Best way to image acute stroke
• Principle rapid-pulse sequence with average
  total time lt2 minutes
• Ischaemia can be visualised as early as within 30
  minutes of stroke
• Relies on reduction of random diffusion (Brownian
  motion) of water after acute stroke

MRI scan

• Features of ischaemic region
• Swollen cells
• Reduced extracellular space
• Decrease in diffusion of water molecules

Ischaemic region
45
Computed tomography (CT) scan
A
B
Chronic infarction
Early ischaemic changes
46
Computed tomography (CT) scan
47
Magnetic resonance imaging (MRI)
Early ischaemic changes after occlusion of the
left internal carotid artery
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Diffusion-weighted imaging (DWI) MRI
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Ischaemic damage

• Determinants of damage
• Duration of cerebral hypoperfusion
• Degree of cerebral hypoperfusion

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Ischaemic stroke prevention and treatment

• The first goal is to restore blood flow
  (thrombolysis)
• Prophylaxis of subsequent ischaemic strokes with
  antiplatelets such as acetylsalicylic acid

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Thrombolytics (t-PA)

• Some exclusion criteria for thrombolytics
• Should preferably be given within 3 hours of
  symptom onset
• No other likely explanation for the neurologic
  symptoms
• No significant risk of bleeding
• No evidence of bleeding on head CT scans
• No evidence of early infarct sign on head CT scan
• Benefit
• 30 likely to have minimal or no disabilities
  after 3 or 12 months
• Adverse effects (5)
• Significant brain haemorrhage

52
Antiplatelets
After first stroke

• Acetylsalicylic acid (ASA)
• Small benefit within 48 hours of stroke onset
• Delay for 24 hours if receiving thrombolytics
• After recurrent stroke with taking ASA
• Consider clopidogrel or dipyramidole/aspirin

53
Neuroprotective therapy
Neuroprotective therapy is designed to save the
penumbra, or the area surrounding the core of the
primary ischaemia, from the damage caused by
reduced blood flow to this region

• Neuroprotection targets
• Calcium channels
• Glutamate receptors
• Free radicals
• Nitric oxide
• Proteases
• Cell membrane components
• Apoptotic pathway molecules(e.g. Bcl-2 promoters)