Undergraduate Neuroscience Teaching
Half Day Teaching on Stroke
Who gets stroke and why
Martin M Brown
Professor of Stroke Medicine
UCL Institute of Neurology
Queen Square, London
Slides at http://www.ucl.ac.uk/ion/departments/sobell/Research/NWard
Objectives
At the end of the lecture you should:
• Have an idea of the impact of stroke in a
population
• Be able to classify stroke according to
pathophysiological abnormalities
• Be familiar with the major risk factors for
vascular disease
• Understand how risk factors lead to
ischaemic and haemorrhagic stroke
Syndrome definitions
• Stroke
– Acute focal cerebral deficit resulting from
vascular disease lasting > 24 hours
• Transient ischaemic attack (TIA)
– Acute focal cerebral deficit resulting from
vascular disease lasting < 24 hours*
• Brain attack
– Acute focal cerebral deficit likely to be the
result of vascular disease
*Some modern definitions classify symptoms as stroke if DWI
shows a relevant acute infarct, irrespective of duration
Burden of stroke in UK
• Annual incidence
– 150,000 strokes* (110,000 are first stroke)
– 20,000 TIAs
– 300 admitted to average DGH,
– 1,800 to UCLH HASU
• 12% of all deaths
• 450,000 disabled as a result of stroke
• Commonest cause of adult disability
• Hospital costs are 5% of NHS Budget
*similar to the number of heart attacks/year in UK
Annual incidence of stroke per 1,000
person years – Oxfordshire Community
Bamford et al JNNP 1990;53:16-22
Cumulative future probability of
stroke in an individual aged 45
Age reached
(years)
65
Men
(% with
stroke)
3
Women
(% with
stroke)
3
75
10
6
85
24
18
90
33
28
Classification of stroke by
macroscopic pathology
• Cerebral infarction (ischaemic stroke)
– 90% of stroke in well developed countries
• Cerebral haemorrhage
– Intracranial haemorrhage (haemorrhagic stroke)
• 5% of stroke
– Subarachnoid haemorrhage (SAH)
• 5% of stroke
Ischaemic stroke is due to occlusion of a cerebral artery by thrombus
CT Scan
showing a
very large
infarct in
the whole
of the MCA
territory
Ischaemic stroke is due to occlusion of a cerebral artery by thrombus
Thrombosis is attributable to any
Virchow’s triad …..
1.
2.
3.
Abnormality in vessel wall (atherosclerosis, dissection,
lipohyalinosis)
Abnormality of blood (e.g. polycythaemia, thrombophilia)
Disturbances of blood flow (e.g. atrial fibrillation)
Two main types of thrombus….
1.
2.
Platelets (fast flow areas such as ICA stenosis)
Fibrin and red blood cells (slow flow areas such as cardiac
atria in AF)
Sources of thrombus in ischaemic stroke
Platelet clots
Fibrin clots
Classification by mechanism: Ischaemic stroke
Large Artery
Disease 26%
Other 8%
Cardioembolism 28%
Lausanne Stroke Registry 1996-2003, n=2,415
Carrera E Cerebrovasc Dis 2007;24:97–103
What do we mean by large arteries?
The internal carotid artery is the commonest site at
which arterial disease develops and causes stroke
What do we mean by small arteries?
What do we mean by small arteries?
Brain cross section showing the arteries after injection of contrast
Disease causing artery narrowing:
Atherosclerosis
Greek origin: Athero, gruel or porridge +
Sclerosis, induration or hardening
Modern terms: Fatty deposits (cholesterol) +
Fibrosis (smooth muscle proliferation)
Causes of ischaemic stroke (1)
• Embolism (thrombus, calcific debris,
atheromatous material, vegetations)
– Cardiac source
• Valvular heart disease
• Atrial fibrillation
• Myocardial infarction
– Carotid or vertebral artery source
• Atheroma
• Dissection
Causes of ischaemic stroke (2)
• Thrombosis in situ
– Major vessel occlusion
– Small vessel disease (lacunar stroke)
• Microatheroma
• Lipo-hyaline degeneration
– Venous occlusion
Rarer causes of ischaemic stroke
•
•
•
•
•
•
•
•
•
Dissection
Vasculitis & SLE
Drug induced
Migraine
Meningitis
Endocarditis
Paradoxical embolism
Atrial myxoma
Haemodynamic stroke
• Antiphospholipid
syndrome
• Fabry’s disease
• Moyamoya disease
• Homocysteinuria
• CADASIL
• MELAS
• Cerebral venous
thrombosis
Normal
internal
carotid
artery
Dissected
internal
carotid
artery
Axial T2 weighted MRI scan
Intracerebral haemorrhage
• Common causes
– Small vessel disease (lipohyaline degeneration)
secondary to Hypertension
and Ageing (50%)
– Ruptured saccular
aneurysms and AVM’s
(30%)
– ICH associated with
bleeding disorders (10%)
– Cerebral Amyloid
Angiopathy (10%)
• Rarer causes
– tumours
– haemorrhagic
infarction
– cerebral vasculitis
– sympathomimetic
drugs
– mycotic aneurysms
– herpes simplex
encephalitis
– haemorrhagic
leukoencephalopathy
Common sites of ICH
Putamen
Lobar
(subcortical)
Cerebellum
Thalamus
Pons
Chronic hypertension leads to vasculopathy of small
perforating arteries, characterised by lipohyalinosis,
fibrinoid necrosis, and the formation of Charcot-Bouchard
micro-aneuryms.
Cerebral Amyloid Angiopathy
• Common cause of ICH in elderly
• Mostly sporadic, few AD families
• multiple , subcortical (especially
occipital and parietal lobes)
• Pathological changes found in
10% of septuagenarians and in
60% of those over 90 yrs.
• Association between CAA and
Alzheimer type pathology
• 10-30% of those with CAA have
a progressive dementia.
Prognosis of stroke
30-day
fatality
rate
1-year
fatality
rate
Survivors
dependent
at 1 year
All strokes 19
31
35
All infarcts 10
23
35
Lacunar
infarcts
1
10
34
ICH
50
62
32
SAH
46
48
24
Numbers are proportions (%)
Risk factors for stroke - 1
• Non-modifiable risk factors
– Increasing age
– Sex
– Family history
– Ethinicity
NB Risk factors are not causes, nor are
they useful in diagnosis!
They are factors that identify or promote
progression of arterial or heart disease or
promote thrombosis
Risk factors for stroke - 2
• Potential modifiable life style risk
factors
– Smoking
– Excess alcohol
– Obesity
– Poor diet
– Lack of exercise
– Lower socio-economic status
– Oestrogen containing OCPs
Risk factors for stroke - 3
• Common modifiable disease risk factors
– Transient ischaemic attack
– Hypertension
– Diabetes mellitus
– Hyperlipidemia
– Cardiac disease
• Ischaemic heart disease
• Cardiac failure
• Atrial fibrillation
– Carotid stenosis
– Peripheral vascular disease
Risk factors for stroke - 4
• Less common disease risk factors
– Polycythaemia
– Thrombocythaemia
– Hyperlipidaemias
– Sickle cell disease
– Migraine
Risk factor
Increasing age (55-64 v > 75 years)
Hypertension (160/95 versus 120/80)
Relative risk
for stroke
5
7
Smoking (current status)
Diabetes mellitus
Social class ( I versus V )
Ischaemic heart disease
Heart failure
Atrial fibrillation
Past TIA
Obesity
Physical activity (Little or none v. some)
2
2
1.6
3
5
5
5
4
2.5
NB Risk factors don’t add together, they multiply together
Objectives revisited
At the end of the lecture you should:
• Have an idea of the impact of stroke in a
population
• Be able to classify stroke according to
pathophysiological abnormalities
• Be familiar with the major risk factors for
vascular disease
• Understand how risk factors lead to
ischaemic and haemorrhagic stroke