‘Stroke Management’‘Stroke Management’

Consultant Neurologist and Honorary Senior Lecturer

Barts and The London NHS TrustLondon Bridge Hospital

Consultant Neurologist and Honorary Senior Lecturer

Barts and The London NHS TrustLondon Bridge Hospital

Dr Ben Turner

IntroductionIntroduction Stroke is the major cause of disability in the

developed world in 1999, there were 56,000 deaths in England

and Wales from stroke Most people survive a first stroke, but often

have significant morbidity. 98,000 people have a first or recurrent stroke

annually More than 900,000 people in England are

living with the effects of stroke, with half of these being dependent on other people for help with everyday activities.

Stroke is the major cause of disability in the developed world

in 1999, there were 56,000 deaths in England and Wales from stroke

Most people survive a first stroke, but oftenhave significant morbidity.

98,000 people have a first or recurrent stroke annually

More than 900,000 people in England are living with the effects of stroke, with half of these being dependent on other people for help with everyday activities.

‘Stroke Management’‘Stroke Management’

Is it a stroke ?

Acute Management of Stroke – some insight

Secondary Prevention

Is it a stroke ?

Acute Management of Stroke – some insight

Secondary Prevention

Is it a stroke ?Is it a stroke ?

Sudden onset

Focal onset

Negative symptoms

Sudden onset

Focal onset

Negative symptoms

Stroke MimicsStroke Mimics

Stroke MimicsStroke Mimics

What type of stroke ?What type of stroke ?

Ischaemic stroke – 50% large artery atherosclerosis, 25% atrial fibrillation, 20% small vessel disease

Intracerebral Haemorrhage – 10% of stroke

Subarachnoid haemorrhage

Others, carotid dissection, cerebral sinus thrombosis

Ischaemic stroke – 50% large artery atherosclerosis, 25% atrial fibrillation, 20% small vessel disease

Intracerebral Haemorrhage – 10% of stroke

Subarachnoid haemorrhage

Others, carotid dissection, cerebral sinus thrombosis

Clinical Stroke Syndromes(The Oxford Bamford Classification)

Clinical Stroke Syndromes(The Oxford Bamford Classification)

Anterior circulation - TACI/PACI (15/35%) Unilateral motor deficit Homonymous hemianopia Higher cerebral function (e.g. dysphasia, neglect)

Posterior circulation - POCI (25%) Bilateral/crossed sensory-motor Pure hemianopia Diplopia & CN palsy Cerebellar signs

Lacunar – LACI (25%) Pure motor (50%) Pure sensory (5%) Ataxic hemiparesis (10%) Sensorimotor stroke (35%)

Anterior circulation - TACI/PACI (15/35%) Unilateral motor deficit Homonymous hemianopia Higher cerebral function (e.g. dysphasia, neglect)

Posterior circulation - POCI (25%) Bilateral/crossed sensory-motor Pure hemianopia Diplopia & CN palsy Cerebellar signs

Lacunar – LACI (25%) Pure motor (50%) Pure sensory (5%) Ataxic hemiparesis (10%) Sensorimotor stroke (35%)

Larg

e Ve

ssel

Smal

l Ves

sel

Thrombolysis for StrokeThrombolysis for Stroke Majority of strokes due to ischaemic emboli Thrombolytic agents been used to dissolve

clot and restore blood supply to brain Problems with haemorrhage into infarcted

area Established evidence base showing

effectiveness of thrombolysis

Majority of strokes due to ischaemic emboli Thrombolytic agents been used to dissolve

clot and restore blood supply to brain Problems with haemorrhage into infarcted

area Established evidence base showing

effectiveness of thrombolysis

Evidence for thrombolysisEvidence for thrombolysis NINDS Trial 1995 Randomised, placebo controlled blinded trial Participants Ischaemic stroke ( CT done to exclude

haemorrhage) Clearly defined time of onset <180 minutes of symptom onset Age between 18 and 80

NINDS Trial 1995 Randomised, placebo controlled blinded trial Participants Ischaemic stroke ( CT done to exclude

haemorrhage) Clearly defined time of onset <180 minutes of symptom onset Age between 18 and 80

Cochrane systematic review of the evidence for thrombolytic therapy in acute ischaemic stroke

Joanna Wardlawabstract available free at:

www.dcn.ed.ac.uk/csrgor on CDROM

The Cochrane Library

Risk of death dependency and good functional outcome in randomised trials of rt-PA given

within 3 hours of acute stroke

Cochrane September 1999

Death and Intracranial Haemorrhage

Death and Intracranial Haemorrhage

Results from 4 trials using rt-PA Death from all causes within 1st 7-10 days OR 1.24 (95% CI 0.85-1.81, p=0.3)

Fatal intracranial haemorrhage 25 extra fatal intracranial haemorrhages per 1000

patients treated OR 3.6, 95% CI 2.28-5.68, p<0.00001

Symptomatic intracranial haemorrhage 62 extra haemorrhages per 1000 patients treated OR 3.13, 95% CI 2.34 - 4.19, p<0.00001

Results from 4 trials using rt-PA Death from all causes within 1st 7-10 days OR 1.24 (95% CI 0.85-1.81, p=0.3)

Fatal intracranial haemorrhage 25 extra fatal intracranial haemorrhages per 1000

patients treated OR 3.6, 95% CI 2.28-5.68, p<0.00001

Symptomatic intracranial haemorrhage 62 extra haemorrhages per 1000 patients treated OR 3.13, 95% CI 2.34 - 4.19, p<0.00001

Time is brainTime is brain

The European Cooperative Acute Stroke Study 3 (ECASS 3)

The European Cooperative Acute Stroke Study 3 (ECASS 3)

confirmed benefit of IV tPA therapy in the 3-to 4.5-hour window.

821 patients were randomized to IV tPA or placebo.

The proportion of patients with minimal or no disability increased from 45% with placebo to 52% with tPA,

NNT for normal outcome 14, improved 8 For every 100 treated 16 better outcome, 3

worse

confirmed benefit of IV tPA therapy in the 3-to 4.5-hour window.

821 patients were randomized to IV tPA or placebo.

The proportion of patients with minimal or no disability increased from 45% with placebo to 52% with tPA,

NNT for normal outcome 14, improved 8 For every 100 treated 16 better outcome, 3

worse

NICE 2012 GuidanceNICE 2012 Guidance Alteplase is recommended within its marketing

authorisation for treating acute ischaemic stroke in adults if:

treatment is started as early as possible within 4.5 hours of onset of stroke symptoms, and

intracranial haemorrhage has been excluded by appropriate imaging techniques.

Alteplase is recommended within its marketing authorisation for treating acute ischaemic stroke in adults if:

treatment is started as early as possible within 4.5 hours of onset of stroke symptoms, and

intracranial haemorrhage has been excluded by appropriate imaging techniques.

Cost effectivenessCost effectiveness

if eligible patients were treated with rt-PA 78% probability of a gain in quality-adjusted survival during

the 1st year at a cost of £13,581 per QALY lifetime cost saving of £96,565 per QALY

if eligible patients were treated with rt-PA 78% probability of a gain in quality-adjusted survival during

the 1st year at a cost of £13,581 per QALY lifetime cost saving of £96,565 per QALY

Intra-arterial Fibrinolytic TherapyIntra-arterial Fibrinolytic Therapy Most recently, the Middle Cerebral Artery Embolism Local

Fibrinolytic Intervention Trial (MELT) investigated intra-arterial urokinase up to 6 hours after onset in 114 subjects. Favorable trends were noted in good functional outcome and substantial benefits observed in the rate of excellent functional outcome. As a result, intra-arterial fibrinolytic therapy is commonly administered as an off-label therapy for stroke at tertiary centers within 6 hours of onset in the anterior circulation and up to 12-24 hours after onset in the posterior circulation.[31]

Most recently, the Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) investigated intra-arterial urokinase up to 6 hours after onset in 114 subjects. Favorable trends were noted in good functional outcome and substantial benefits observed in the rate of excellent functional outcome. As a result, intra-arterial fibrinolytic therapy is commonly administered as an off-label therapy for stroke at tertiary centers within 6 hours of onset in the anterior circulation and up to 12-24 hours after onset in the posterior circulation.[31]

Challenges to effective thrombolysis

Challenges to effective thrombolysis

Prehospital delays Public awareness of stroke Poor knowledge of symptoms of stroke FAST test

Poor awareness of early treatments available Late presentation

Ambulance response Need for “Blue-light” calls

Prehospital delays Public awareness of stroke Poor knowledge of symptoms of stroke FAST test

Poor awareness of early treatments available Late presentation

Ambulance response Need for “Blue-light” calls

Current Stroke PathwayCurrent Stroke Pathway

Eligible Patients Age 18-80 years Confirmed diagnosis of ischaemic stroke Onset less than 4.5 hours before initiation

of treatment

Eligible Patients Age 18-80 years Confirmed diagnosis of ischaemic stroke Onset less than 4.5 hours before initiation

of treatment

Contra-indications to thrombolysis

Contra-indications to thrombolysis

Minor or rapidly improving symptoms (no motor features, < 4 NIHSS) Severe stroke (NIHSS >25) Fit at stroke onset History consistent with subarachnoid haemorrhage (even if CT normal) Stroke or head injury resulting in LOC > 2 mins in the last 3 months History of intracranial bleeding History of arteriovenous malformation or aneurysm History of prior stroke and concomitant diabetes Recent (within 1 week ) lumbar puncture Any history of central nervous system damage (e.g. neoplasm,

intracranial or spinal surgery)

Minor or rapidly improving symptoms (no motor features, < 4 NIHSS) Severe stroke (NIHSS >25) Fit at stroke onset History consistent with subarachnoid haemorrhage (even if CT normal) Stroke or head injury resulting in LOC > 2 mins in the last 3 months History of intracranial bleeding History of arteriovenous malformation or aneurysm History of prior stroke and concomitant diabetes Recent (within 1 week ) lumbar puncture Any history of central nervous system damage (e.g. neoplasm,

intracranial or spinal surgery)

Contra-indications to thrombolysis

Contra-indications to thrombolysis

Pregnancy Evidence of active bleeding Major surgery or trauma within the last 14 days Pancreatitis History of GI bleeding, liver disease or oesophageal varices Arterial puncture at a non-compressible site Pericarditis BP>185/110 after treatment Abnormal APTT, coagulopathy Platelet count below 100,000/mm3 Hyper or hypoglycaemia Oral anticoagulants or heparin therapy

Pregnancy Evidence of active bleeding Major surgery or trauma within the last 14 days Pancreatitis History of GI bleeding, liver disease or oesophageal varices Arterial puncture at a non-compressible site Pericarditis BP>185/110 after treatment Abnormal APTT, coagulopathy Platelet count below 100,000/mm3 Hyper or hypoglycaemia Oral anticoagulants or heparin therapy

Summary of ThrombolysisSummary of Thrombolysis

Thrombolysis increases the odds of a favourable outcome 8 times if given within 90 minutes, x2 at 91 -180 minutes.

Case fatality not affected if given up to 270 minutes.

Haemorrhagic transfromation associated with increasing age and larger infarcts.

Thrombolysis increases the odds of a favourable outcome 8 times if given within 90 minutes, x2 at 91 -180 minutes.

Case fatality not affected if given up to 270 minutes.

Haemorrhagic transfromation associated with increasing age and larger infarcts.

Thrombolysis NNTThrombolysis NNTNational Audit Office (2007). Joining Forces to Deliver Improved Stroke Care. NAO.

Other Scenario’sOther Scenario’sStroke > 6 hours

Aspirin - 300mg then 75 to 150mg prevents 15 dependencies or deaths per 1000 patients treated.

Low molecular weight heparin - increased haemorrhagic transformation negates the reduced ischaemic recurrence.

Stroke > 6 hours

Aspirin - 300mg then 75 to 150mg prevents 15 dependencies or deaths per 1000 patients treated.

Low molecular weight heparin - increased haemorrhagic transformation negates the reduced ischaemic recurrence.

NICE guidelinesNICE guidelines Non- acutely for people who have had an

ischaemic stroke, clopidogrel is recommended as a treatment option. For people who have a contraindication or intolerance to clopidogrel, modified-release dipyridamole plus aspirin is recommended as a treatment option. For people who have a contraindication or intolerance to both clopidogrel and aspirin, modified-release dipyridamole alone is recommended as a treatment option.

Non- acutely for people who have had an ischaemic stroke, clopidogrel is recommended as a treatment option. For people who have a contraindication or intolerance to clopidogrel, modified-release dipyridamole plus aspirin is recommended as a treatment option. For people who have a contraindication or intolerance to both clopidogrel and aspirin, modified-release dipyridamole alone is recommended as a treatment option.

Transient Ischaemic Attacks (TIA’s)

Transient Ischaemic Attacks (TIA’s)

Acute loss of focal or monocular function with symptoms lasting < 24 hoursStroke risk8% in first week12 % at one month17% at three months

Acute loss of focal or monocular function with symptoms lasting < 24 hoursStroke risk8% in first week12 % at one month17% at three months

Six point ‘ABCD’ score for stroke risk after TIA

Six point ‘ABCD’ score for stroke risk after TIA

Age> 60 = 1, < 60 = 0

Blood Pressuresystolic > 140 / diastolic > 90 = 1systolic < 140 and diastolic < 90 = 0

Clinical featuresunilateral weakness = 2speech disturbance, no weakness = 1other = 0

Duration of symptoms (minutes)> 60 = 2, 10-59 = 1, <10 = 0

Age> 60 = 1, < 60 = 0

Blood Pressuresystolic > 140 / diastolic > 90 = 1systolic < 140 and diastolic < 90 = 0

Clinical featuresunilateral weakness = 2speech disturbance, no weakness = 1other = 0

Duration of symptoms (minutes)> 60 = 2, 10-59 = 1, <10 = 0

TIA Management in A&ETIA Management in A&E All Patients

CT/CTA & ECG Start ASA

Admit if Atrial Fibrillation (unless FRT) Carotid stenosis (for surgery) >2 in 1 week (for Ix) ABCD2 >4 and no clinic in 24hrs

If ABCD2 < 4 & none of above Can refer to local TIA clinic

All Patients CT/CTA & ECG Start ASA

Admit if Atrial Fibrillation (unless FRT) Carotid stenosis (for surgery) >2 in 1 week (for Ix) ABCD2 >4 and no clinic in 24hrs

If ABCD2 < 4 & none of above Can refer to local TIA clinic

NICE guidelines for TIANICE guidelines for TIA

For people who have had a transient ischaemic attack, modified-release dipyridamole plus aspirin is recommended as a treatment option. For people who have a contraindication or intolerance to aspirin, modified-release dipyridamole alone is recommended as a treatment option.

For people who have had a transient ischaemic attack, modified-release dipyridamole plus aspirin is recommended as a treatment option. For people who have a contraindication or intolerance to aspirin, modified-release dipyridamole alone is recommended as a treatment option.

Management for CVA and TIAManagement for CVA and TIA

Detection of life threatening emergencies – aspiration , seizures

Stabilisation of physiological parameters- hypoxaemia, hyperglycaemia, dehydration

Detection of life threatening emergencies – aspiration , seizures

Stabilisation of physiological parameters- hypoxaemia, hyperglycaemia, dehydration

Investigation of Stroke and TIAInvestigation of Stroke and TIAFirst line Clinical examination FBC – polycythaemia, thrombocythaemia ESR/CRP – infection / vasculitis Glucose Urea and Electrolytes ECG Carotid Duplex

First line Clinical examination FBC – polycythaemia, thrombocythaemia ESR/CRP – infection / vasculitis Glucose Urea and Electrolytes ECG Carotid Duplex

Investigation of Stroke and TIAInvestigation of Stroke and TIA

Second line Echocardiogram 24 hour ECG Angiography Specialised biologic tests – dsDNA,

cardiolipin ab’s , syphilis serology etc

Second line Echocardiogram 24 hour ECG Angiography Specialised biologic tests – dsDNA,

cardiolipin ab’s , syphilis serology etc

Secondary PreventionSecondary Prevention

Non-modifiable risk factors Age Male gender Familial predisposition

Non-modifiable risk factors Age Male gender Familial predisposition

Secondary PreventionSecondary PreventionModifiable risk factors Blood Pressure - risk double for every 7.5mmHg in

diastolic BP

Blood Cholesterol – total and LDL, low HDL

Smoking – doubles risk

Diabetes Mellitus – doubles risk

Oral Contraceptive pills - high oestrogen (>50ug) high risk , but still 1 per 200,000 woman years, thrombosis is increased at both doses

HRT - increases risk of ischaemic stroke

Modifiable risk factors Blood Pressure - risk double for every 7.5mmHg in

diastolic BP

Blood Cholesterol – total and LDL, low HDL

Smoking – doubles risk

Diabetes Mellitus – doubles risk

Oral Contraceptive pills - high oestrogen (>50ug) high risk , but still 1 per 200,000 woman years, thrombosis is increased at both doses

HRT - increases risk of ischaemic stroke

Anticoagulation in AFAnticoagulation in AF

NICE Guidelines for AF NICE Guidelines for AF CHA2DS2-VASc stroke risk score

aged 65–74 years (1 point) aged 75 years or older (2 points) female (1 point) congestive heart failure (1 point) hypertension (1 point) diabetes (1 point) stroke, transient ischaemic attack or thromboembolism

(2 points) vascular disease – previous myocardial infarction, peripheral

arterial disease, aortic plaque (1 point).

CHA2DS2-VASc stroke risk score

aged 65–74 years (1 point) aged 75 years or older (2 points) female (1 point) congestive heart failure (1 point) hypertension (1 point) diabetes (1 point) stroke, transient ischaemic attack or thromboembolism

(2 points) vascular disease – previous myocardial infarction, peripheral

arterial disease, aortic plaque (1 point).

Anticoagulants in AF Anticoagulants in AF Available options should include

vitamin K antagonists (such as warfarin) and non-vitamin K antagonist oral anticoagulants (NOACS; that is, apixaban, dabigatran etexilate and rivaroxaban). In adults with valvular atrial fibrillation, only vitamin K antagonists can be used, and this should be explained to the person.

Available options should include vitamin K antagonists (such as warfarin) and non-vitamin K antagonist oral anticoagulants (NOACS; that is, apixaban, dabigatran etexilate and rivaroxaban). In adults with valvular atrial fibrillation, only vitamin K antagonists can be used, and this should be explained to the person.

Benefits of BP LoweringBenefits of BP Lowering

Cholesterol Lowering Benefits

Summary

Dr Ben Turner

Private Secretary 020 7234 2694

enquiries@drbenturner.com

www.drbenturner.com

NHS benjamin.turner@bartsandthelondon.nhs.uk