Strokes

Front 1

3rd most common cause of death

Back 1

cerebrovascular disease

Front 2

TIA

Back 2

Transient ischemic attack: a cerebrovascular event causing neurological symptoms or signs lasting less than 24 h (usually 1- 30 min).
NB: warning sign for completed stroke (5% risk in first week)

Front 3

Types of stroke

Back 3

80% infarction
20% hemorrhage

Front 4

Causes of Stroke

Back 4

Infarction (ischemic and hemorrhagic)
Large artery athero-thrombosis
Small penetrating artery occlusion
Embolism (often hemorrhagic)
Global ischemia (cerebral hypoperfusion)
Hemorrhage
Intracerebral hemorrhage
Subarachnoid hemorrhage

Front 5

1. Large artery athero-thrombosis
SITES

Back 5

1. Extracranial vessels commonest site for atherosclerosis, especially internal carotid artery near common carotid bifurcation
2. Intracranial vessels: especially at origin of middle cerebral artery and ends of basilar artery

Front 6

Acute Brain Infarct CHANGES

Back 6

Softening
Swelling (raised intracranial pressure can cause brain stem compression and death)
Neutrophils
Ischemic (“red cell”) neuronal change

Front 7

Brain infarct: post-acute

Back 7

Foamy macrophages (start at about 3 days) - remove debris
Reactive astrocytes (start at about 10 days) - form glial scar
Cavitation

Front 8

Acute ischemia
Molecular events

Back 8

1. Decreased energy production
Failure of ionic pumps
Mitochondrial injury produces free radicals
2. Glutamate release
Increased intracellular calcium
Stimulation of reactive intermediates leading to membrane and DNA damage

Front 9

Brain infarct; Pathophysiology

Back 9

Neuronal electrical failure develops at 30% normal cerebral blood flow
Membrane failure develops at 15% normal cerebral blood flow
Ischemic penumbra retains viability if blood flow is restored
Some neurons more resistant to hypoxia (possibly due to different surface receptors)

Front 10

2. Small penetrating artery occlusion

Back 10

aka LACUNAR INFARCT
Occlusion (arterial wall fibrous thickening or atheroma) of a small penetrating artery
Causes small (up to 20 mm) infarct in deep structures of brain (basal ganglia, thalamus, internal capsule) and in the brain stem
Associated with arterial hypertension
Often clinically silent
Over 20 clinical syndromes, especially pure sensory or motor strokes and transient ischemic attacks

Front 11

secondary stroke or TIA prevention

Back 11

Medications
Anti-platelet agents (e.g., aspirin)
Statins (many different effects)
Anti-hypertensives
Angioplasty or stenting

Front 12

CADASIL

Back 12

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
Presents with TIAs or migraine, can progress to subcortical dementia
Notch 3 receptor gene mutations (also involved in familial hemiplegic migraine)

Front 13

3. Embolism

Back 13

Embolic infarcts are usually peripheral in the brain
Most are hemorrhagic (due to reflow of blood into the damaged area after lysis of the thrombus). These small thrombo-emboli can by lysed (unlike large in situ thrombi)
They may be multiple
Most are in the middle cerebral artery territory
Danger from anticoagulation therapy

Front 14

Sources of Emboli
THROMBO-EMBOLI

Back 14

THROMBO-EMBOLI
Heart
Left atrium
atrial fibrillation ++
mitral stenosis
Left ventricle (myocardial infarction)
Valves (infective or marantic endocarditis)
Artery (carotid artery, aortic arch)
Venous source + cardiac septal defect

Non-thrombotic emboli
Atheroma, cholesterol, calcific debris (from arteries or cardiac valves)
Atrial myxoma
Systemic emboli (fat, air, amniotic fluid)

Front 15

AF

Back 15

About 20% of ischemic strokes and TIAs happen in patients with atrial fibrillation
Aspirin is fairly ineffective to prevent these strokes

Front 16

4. Global ischemia (cerebral hypoperfusion)

Back 16

“Boundary zone” infarcts seen when abrupt hypotension followed by rapid recovery
Autoregulation fails in regions most remote from the main arterial stem, between arteries territories
Infarcts often seen between
Middle and anterior cerebral arteries
Middle and posterior cerebral arteries

Front 17

Venous infarction/hemorrhage

Back 17

Blocked vein causes back pressure on capillaries with leakage of blood into tissue
Superior sagittal sinus especially
White and grey matter affected
Often seen in infants and in pregnancy
Causes
Local (infection, trauma)
Systemic (increased coagulation, dehydration)

Front 18

5. Intracerebral hemorrhage

Back 18

Increasing incidence in many populations (increased no. elderly, increased use of anticoagulants and anti-platelet agents)
Hematoma in cerebrum, cerebellum, or brain stem
Deep intracerebral hemorrhages are associated with hypertension
Hemorrhage can progress (up to 12 h)
Edema around hemorrhage increases, and alters outcome
Hemorrhage resolves to a “slit” lined with hemosiderin-laden macrophages

Front 19

Intracerebral hemorrhage causes

Back 19

Arterial hypertension (deep sites)
Small artery degenerative changes
? microaneurysms
Vascular malformation
Capillary telangiectasia
Arteriovenous malformation
Hemorrhage into a brain tumour
Vascular amyloid (peripheral “lobar” hemorrhage) - same amyloid as in AD (AB), ApoE genotype effect, mutation in APP causes hereditary form
Systemic hemorrhagic disorder (e.g. leukemia, anticoagulants)

Front 20

6. Subarachnoid hemorrhage

Back 20

Symptoms from
Meningeal irritation (e.g. headache)
Increased intracranial pressure (e.g. decreased consciousness)
Vasospasm after bleed
Causes
Ruptured berry aneurysm ++
Arteriovenous malformation

Front 21

Berry Aneurysm

Back 21

Small outpouching at bifurcation of arteries
Most seen at the base of the brain (90% on anterior circulation)
Thin collagenous wall
Found in 2% of the population
May be multiple in 25% of patients
Increased incidence in first degree relatives
If > 10 mm diameter, 50% risk of bleeding per year

Front 22

Berry aneurysm
Possible pathogeneses

Back 22

1. Congenital
Medial defect at arterial bifurcation
Type III collagen deficiency
2. Acquired
Hemodynamic stress at bifurcation
Atherosclerosis
Hypertension

Front 23

Stroke Units

Back 23

–
Acute stroke units which accept patients acutely but discharge early (usually within 7 days).
–
Rehabilitation stroke units which accept patients after a delay of usually 7 days or more and focus on rehabilitation; and
–Comprehensive (ie combined acute and rehabilitation) stroke units

- Stroke unit care includes red. neuronal cell death risk factors such as fever and hyperglycaemia

Front 24

stroke unit outcomes

Back 24

•Reduction in death - 17%
•Reduction in death or institutionalisation - 25%
•Reduction in death or dependency - 31%
•Reduction in length of hospital stay - 8%
•NNT to prevent death : 22
•(NNT to prevent major adverse outcome in mild hypertension : 141)
•(NNT to prevent death or stroke after TIA : 6)

Front 25

Stroke Sx

Back 25

•Amaurosis fugax (transient monocular visual loss)
•(hemi-)paresis / weakness
•Sudden speaking probem
• hemiapnopia
• double vision

Front 26

Stroke Mimicry

Back 26

•Seizure
•Toxic
•Metabolic
•Sepsis
•Syncope
•Confusion
•Vestibular Dysfunction
•Peripheral nerve lesion
•Migraine

Front 27

Stroke DDx

Back 27

•acute onset
•neurologic deficit
•localizing signs
•well in last week

Front 28

TIA: last chance to prevent stroke!

Back 28

•25% risk of a vascular event or death within 90 d
•most of which occur within 48 h
•10% have a major stroke within 7 days
•Urgent assessment and treatment reduces the risk by 80%

Front 29

Risk factors for stroke

Back 29

Front 30

Ddx ischemic and Intracerebral hemorrhage strokes?

Back 30

Same Sx

- these people vomit a little more (unrealiable)

Front 31

tPA Outcomes

Back 31

0 No symptoms at all
1
No significant disability despite symptoms; able to carry out all usual duties and activities
2
Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
3
Moderate disability; requiring some help, but able to walk without assistance
4
Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
5
Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6
Dead

- not increasing mortality cf to placebo even though INC> the risk of bleeds

Front 32

Evolution of brain infarct

Back 32

Front 33

Time is brain

Back 33

Front 34

tPA
why 3 hrs?

Back 34

Front 35

Why do only 3% of all stroke patients receive acute treatment?

Back 35

•57% of all patients present too late (>3h) NSF Stroke audit
•Stroke doesn’t hurt
•No awareness “sleep it off”

Front 36

Endovascular Therapy

Back 36

•Ultrasound (EKOS)
•Shock-wave/ Vacuum: Angiojet
•Retrieval devices (NEED, MERCI)
•Laser devices (EPAR)
•Suction-Devices (Penumbra)
•Stent-retrievers (Solitaire)

Front 37

Endovascular therapy after IV t-PA
VS
tPA alone

Back 37

no different outcomes
- big problem is door to puncture time of greater than 2hrs

Front 38

Aspirin + Clopidogrel?

Back 38

no comparitive benefit
+ added risk esp, if the stroke is haemorrhagic

Front 39

RR of Stroke in AF

Back 39


Warfarin vs Placebo 62% (48 - 72%)

ASA vs Placebo 22% (2 - 38%)

Warfarin vs ASA 36% (14 - 52%)

Front 40

Aggressive medical managment of IC stenosis vs Stenting

Back 40

STENTING; doubles risk of stroke initially but then no added risk thereafter WHEREAS

medical therapy groups slowly catch up in the longer term

Front 41

What predicts survival/recovery?

Back 41

•Age
•Gender
•Severity of illness / condition
- HT is greatest risk factor
•Pre-existing illness or disability
•Use of effective treatments
•Compliance with effective treatments
•Issues related to general health
smoking
alcohol
physical activity
nutritional status
adequate income
marital status

Front 42

Rule of 1/3

Back 42

1 year after stroke
•1/3 die
•1/3 recover
•1/3 have persistent disability

Front 43

Prognosis after a stroke

Back 43

lots of people die early on then they seem to be parallel

Front 44

what time of day do stroke mostly occur?

Back 44

mornings

Front 45

risk if having a stroke following a TIA

Back 45

1 in 5

Front 46

ABCD2
score

Back 46

• Age 60 years or older (1point)
• Blood pressure elevation on first assessment after
TIA -systolic ≥140 mmHg or diastolic ≥90 mmHg (1point)
• Clinical features of TIA (unilateral weakness, 2points;
or speech impairment without weakness, (1point)
• Duration of TIA ≥60 minutes, 2 points; or 10–59
minutes (1 point)
• Diabetes (1 point)

Front 47

Assessing TIA or stroke

Back 47

1. ischaemic or hemorrhage
2. vascular territory involved
3. Pathophysiology of the event
4. vascular risk factors
5. Assoc. vascular disease

Front 48

Stroke Ix

Back 48

1. brain imaging (CT or MRI)
2. vascular imaging- carotid/vertebrobasilar US or CT/MRI angiogram
3. ECG, Echo
4. Blood test - coag screen, cholestrol...

Front 49

Treating an assymptomatic carotid stensois

Back 49

- 1% risk reduction per year

Front 50

Secondary prevention following minor stroke or TIA due to carotid stenosis

Back 50

emergency surgery therefore required

Front 51

Carotid endarterectomy
or carotid stent?

Back 51

- similar rates of death within 30days of surgery, there is a trend though towards surgerybeing more effective
- and after 2yrs similar rates of recurrent ipisilaterals

Front 52

Antiplatelet MOA

Back 52

Front 53

Aspirinr RR

Back 53

13% for stroke

Front 54

Clopidigrel vs Aspirin

Back 54

RRR; 7.3%
- fewer ICH and haemorrhagic deaths too

Front 55

When do you use clopidogrel?

Back 55

- more expensive thus use only when
- risk of GI complications
- an event has occured while on aspirin

Front 56

Dipyridamole and
Aspirin in
secondary prevention of stroke

Back 56

RR compared to placebo
DP; 16%
ASA: 18%
DP + ASA: 37%
- when together doubles RR and no added SE, no added haemorragic SE, except the headache at Tx initation
- also still cheaper than clopidogrel

Front 57

ASA + Clopidogrel

Back 57

- the combo was not significantly more effective than aspirin alone in reducing rates of MI, stroke, or death (CV)

Front 58

Warfarin vs ASA

Back 58

-no benefit over ASA in patients without AF or other cardiac sources of emboli

Front 59

AF risk stratification

Back 59

Front 60

Dabigatran vs Warfarin

Back 60

lower embolism or stroke: 1.11%/year vs 1.69%
- lower rates of haemorragic stroke (0.12% vs 0.38%)

problem;
\no inhibitor of dabigatran
/ no test for anti-coag activity

Front 61

Are all anti-hypertensives equally effective for secondary stroke prevention?

Back 61

- diuretiics, b-blockers, CCB, ACEI, AT2A

all effective

Front 62

What BP should be targeted?

Back 62

130/85 is hypertensive (ASA)

Front 63

Statsins

Back 63

effective in reducing
- major coronary
- any stroke (may be an inc. in haemorrhagic stroke)
- revascularisation
by 1/3 irrespective of age, sex, cholestrol level, other Tx

Front 64

Cholestrol Targets

Back 64

<4 total
<2.5 LDL

Front 65

Smoking

Back 65

INC risk
- 3.7 x stroke
- 9,8 x subarachnoid haemorrhage

STOP smoking the risk drops to baseline by 3-5yrs

Front 66

EtOH

Back 66

- heavy use INC. stroke
- haemorrhage assoc. with binge
- moderate use protective (INC. HDL) 1-1.2 STD female and 2 for males

Front 67

OC & HRT

Back 67

RR: 2.75 in OC (lower the dose of E lower the risk)
RR: 1.2 in HRT but mortality unaffected

Front 68

Cortical Sx of stroke

Back 68

anosagnosie
sensory neglect
dysarthria...

Front 69

Why is stroke a medical emergency?

Back 69

- ischaemic penumbra
- not yet reached the point energy and ion pump failure where the tissue can no longer maintain integrity

Front 70

DW-MRI

Back 70

- maps avergae apparent diffusion coefficient (ADC)
- ADC is red. following a stroke due to cytotoxic oedema (can tell within minutes), normal at week 1 and after that ADC increases

- can be combine with PWI using gadolinium to ID brain tissue that is reduced perfusion but not infarcted (Ischaemic Pneumbra)

Front 71

rTPA

Back 71

- 30% more likely to have minimal or no disability at 3 months
- mortality 17% and 21% placebo
- symptomatic ICH within 36hrs 6.4% rTPA vs 0.6% placebo
- significant benefit upto 4.5hrs

Front 72

MERCI Clot retriever

Back 72

Front 73

Maintenance of perfusion- HT following stroke

Back 73

- autoregulation of cerebral perfusion is lost with acute stroke
- thus DONT lower BP after a stroke until it reaches levels that will cause organ damage

Front 74

Insulin, BG and stroke

Back 74

- hyperglycemia in acute phase related to poor outcome
- insulin has direct protective effect on cerebral ischaemia (IGF-1 mediated)

Front 75

Fever + Stroke

Back 75

elevated temp in acute pahse ahs worse outcomes
- lower temp with paracetamol + cooling

Front 76

Anticoagulation following cardioembolic stroke due to AF

Back 76

- when to start

Front 77

Stroke unit NNT

Back 77

32 for survival
18 to regain independence
16 to return home

Front 78

Essential early care in stroke

Back 78

- document deficits and evalute risk
- estab. pathophysiology and Mx, Px
- Est. Swallowing and prevent aspiration
- monitor vitals
- adquate nutrition and fluids
- establish communication
- bladder and bowels (avoiding catheterization)
- BP managment
- harm minimization
- min. distress (emotional)
- approp. info

Front 79

Relative Efficacy of Stroke Tx

Back 79

NNT
tPA <3hrs = 7
tPA <6hrs = 11
stroke unit = 18
aspirin = 83

Front 80

Cogn. Deficit

Back 80

- usually improve after stroke
- recogn. and appropriate Mx of depression as a major impediment to rehab

Front 81

Rehab

Back 81

MAX. acheived after 12wks (no more improvement should be expected after 5 months)

begin ASAP

Front 82

Salt

Back 82

AVg. red. in BP by 5-7mmHg in HT below 90mmol/day