Dr Ben Turner. Consultant Neurologist and Honorary Senior Lecturer Barts and The London NHS Trust London Bridge Hospital

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1 Stroke Management Dr Ben Turner Consultant Neurologist and Honorary Senior Lecturer Barts and The London NHS Trust London Bridge Hospital

2 Introduction 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.

3 Stroke Management Is it a stroke? Acute Management of Stroke some insight Secondary Prevention

4 Is it a stroke? Sudden onset Focal onset Negative symptoms

5 Stroke Mimics

6 Stroke Mimics

7 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

8 Clinical Stroke Syndromes (The Oxford Bamford Classification) Large Vessel Small Vessel 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%)

9 Thrombolysis 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

10 Evidence 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

11 Cochrane systematic review of the evidence for thrombolytic therapy in acute ischaemic stroke Joanna Wardlaw abstract available free at: or on CDROM The Cochrane Library

12 Risk of death dependency and good functional outcome in randomised trials of rt-pa given within 3 hours of acute stroke Cochrane September 1999

13 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 , p=0.3) Fatal intracranial haemorrhage 25 extra fatal intracranial haemorrhages per 1000 patients treated OR 3.6, 95% CI , p< Symptomatic intracranial haemorrhage 62 extra haemorrhages per 1000 patients treated OR 3.13, 95% CI , p<

14 Time is brain

15 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

16 NICE 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.

17 Cost 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

18 Intra-arterial Fibrinolytic Therapy Most recently, the Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) investigated intraarterial 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 hours after onset in the posterior circulation.[31]

19 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

20 Current Stroke Pathway Eligible Patients Age years Confirmed diagnosis of ischaemic stroke Onset less than 4.5 hours before initiation of treatment

21 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)

22 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

23 Summary of Thrombolysis Thrombolysis increases the odds of a favourable outcome 8 times if given within 90 minutes, x2 at minutes. Case fatality not affected if given up to 270 minutes. Haemorrhagic transfromation associated with increasing age and larger infarcts.

24 Thrombolysis NNT National Audit Office (2007). Joining Forces to Deliver Improved Stroke Care. NAO.

25 Other Scenario s 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.

26 NICE 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.

27 Transient Ischaemic Attacks (TIA s) Acute loss of focal or monocular function with symptoms lasting < 24 hours Stroke risk 8% in first week 12 % at one month 17% at three months

28 Six point ABCD score for stroke risk after TIA Age > 60 = 1, < 60 = 0 Blood Pressure systolic > 140 / diastolic > 90 = 1 systolic < 140 and diastolic < 90 = 0 Clinical features unilateral weakness = 2 speech disturbance, no weakness = 1 other = 0 Duration of symptoms (minutes) > 60 = 2, = 1, <10 = 0

29 TIA 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) ABCD 2 >4 and no clinic in 24hrs If ABCD 2 < 4 & none of above Can refer to local TIA clinic

30 NICE 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.

31 Management for CVA and TIA Detection of life threatening emergencies aspiration, seizures Stabilisation of physiological parameters - hypoxaemia, hyperglycaemia, dehydration

32 Investigation of Stroke and TIA First line Clinical examination FBC polycythaemia, thrombocythaemia ESR/CRP infection / vasculitis Glucose Urea and Electrolytes ECG Carotid Duplex

33 Investigation of Stroke and TIA Second line Echocardiogram 24 hour ECG Angiography Specialised biologic tests dsdna, cardiolipin ab s, syphilis serology etc

34 Secondary Prevention Non-modifiable risk factors Age Male gender Familial predisposition

35 Secondary Prevention 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

36 Anticoagulation in AF

37 NICE Guidelines for AF CHA 2 DS 2 -VASc stroke risk score aged 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).

38 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.

39 Benefits of BP Lowering

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41 Cholesterol Lowering Benefits

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44 Summary

45 Dr Ben Turner Private Secretary NHS