Transient Ischaemic Attacks Dr Gillian Mead

Overview Definition Making the diagnosis (and common differentials) Risk Stratification Investigation Management

What is a TIA? Clinical definition (1st appeared in 1950’s) Abrupt onset Focal neurological symptoms/deficit includes monocular blindness Last less than 24 hours Presumed to be “vascular” in origin after “appropriate” investigation

FOCAL neurological symptoms weakness of face / arm /leg on one side sensory disturbance of face / limbs on one side * ** amaurosis fugax (transient monocular blindness) language disorder (aphasia) homonymous visual field loss sudden bilateral blindness diplopia* dysarthria* * caution if this is the only symptom ** caution if the sensory symptoms only last minutes

NON-FOCAL neurological symptoms (= NOT TIA) loss of consciousness faintness generalised weakness Vertigo only drop attacks confusional episodes

The importance of an accurate diagnosis Explanation of the symptoms for the patient Guides the search for underlying pathology sources of embolism disease of large or small blood vessels haematological problem haemodynamic problems Prognosis Appropriate management Driving advice 1/12 for single TIAs, 3/12 for frequent TIAs HGV: different rules apply

The diagnosis is not always easy Many patients referred with TIAs to hospital have not had them Only moderate inter-rater reliability even between experts Pattern recognition is important Good history (may need to ask a witness) Ask the right questions Lots of clinical experience

Diagnoses made in patients referred to a Neurovascular clinic Cardiac syncope Cough/micturition syncope Postural hypotension Hyperventilation Sleep apnoea Hypoglycaemia Neurological problems Migraine (+/- headache) Epilepsy Transient global amnesia Glioma Meningioma Cerebral metastases Subdural haematoma Lymphocytic meningitis Peripheral neuropathy Guillain–Barré syndrome Cervical myelopathy Brachial neuritis Herpes Zoster neuropathy Bell’s palsy Syringobulbia Myasthenia gravis Multiple sclerosis Motor neurone disease Psychiatric problems Somatisation disorder Ophthalmic problems Retinal vein occlusion Glaucoma

85 year old man Referred to CAA with recurrent episodes of right arm weakness Diagnosis of TIA Referred to stroke team Detailed history: writing had ‘not been right’ for a few weeks CT brain showed left hemisphere metastases

Mr B, a 41 year old male 3 weeks, episodes of ‘tingling’ and paraesthesia over part of the left arm and upper part of left leg Attacks became more severe and more frequent, & involved the whole of the left side of the body. Symptoms spread: from the hand to the head over one minute.

Mr B, a 41 year old male No cerebrovascular or cardiovascular disease Ex-smoker. BP 140/75 Examination normal Diagnosis: transient ischaemic attacks

CT scan CT showed a glioma in right sensory cortex Attacks were NOT TIA; the correct diagnosis was sensory epileptic seizures

50 year old lady At work, sudden onset of left arm tingling and very mild weakness Referred to stroke team as ? Stroke o/e left arm drift, subjective reduced sensation. On direct questioning, reported dull headache starting a few hours afterwards No vascular risk factors Had migraine in her 20s, none recently CT brain normal Referred to neurology: MRI showed small deep infarct in right internal capsule, based on history, diagnosis was migraine, infarct was a result of vasospasm

Bilateral subdural haematoma This scan shows low density areas (arrows) over the surface of the cerebral hemispheres. These are due to blood in the subdural space. More often the bleeding is on one side and can mimic a stroke although the symptoms usually come on more slowly. The blood can be removed surgically. Often such bleeding occurs after head injury and in patients taking anticoagulants

A brain tumour This shows a rounded lesion (white ) with surrounding swelling (black). The tumour itself is showing up white because the radiologist has injected a dye (contrast media) which is taken up by the tumour. This is a brain tumour which can sometimes produce symptoms similar to those of a stroke. Typically however the symptoms of a brain tumour would worsen over days or weeks rather than coming on over minutes or hours.

Diagnosing TIAS Invite any witnesses to the consultation See the patient as early as possible after the event Take a full narrative history of event Collect circumstantial evidence from history Investigate to collect further circumstantial evidence

Important points from history Demographic details Onset and time course Number of events and duration Precipitating factors (position,drugs etc) Nature of symptoms Vascular risk factors or relevant co-morbidity

Risk Stratification

High early risk of stroke after TIA 14 OXVASC OCSP 12 10 8 Risk of stroke (%) 6 10% risk of stroke by 7 days 4 2 7 14 21 28 Days Lancet 2005; 366: 29-36

ABCD2 Score Factor Category Score Age Age≥60 Age<60 1 Blood pressure at assessment SBP>140 or DBP≥90 Other Clinical Features Unilateral weakness Speech disturbance (no weakness) 2 Duration ≥60 minutes 10-59 minutes <10 minutes Diabetes Yes No And here is the score Age over 60 and SBP>140 or DBP>=90 score one- otherwise zero Any unilateral weakness score scores 2 while speech disturbance without weakness scores 1 Symptom duration was categorised around 10 and 60 minutes, scoring 2, one or zero.

Stroke risk (%) Score 1-3 LOW 2-day risk* 1% Score 4-5 MODERATE HIGH risk 8% Stroke risk (%) Johnstone Lancet 2007 369 283-9

Refining ones prognosis Factors associated with increased risk of stroke Increasing age Brain TIAs Number of recent TIAs Peripheral vascular disease Carotid stenosis percentage ulceration/irregularity

Routine Investigations Full blood count Erythrocyte sedimentation rate Urea & Electrolytes Blood glucose Cholesterol ECG

Investigations on selected patients Carotid Duplex (for pts with carotid TIAs) CT Brain scan or MRI (for multiple cerebral attacks) Echocardiogram 24 hour ECG Lupus anticoagulant Thrombophilia screen

Treatment strategy Treat any specific underlying cause Modify vascular risk factors Smoking Diabetes Specific therapies Antiplatelets drugs Antihypertensives statins Anticoagulants Carotid endarterectomy

Days from medical attention EXPRESS: Clinic-referred population 2 4 6 8 10 30 60 90 Days from medical attention Risk of stroke (%) NV clinic P<0.0001 Same day clinic HIGHER-RISK CASES – FASTER – 5%.

TIA hotline introduced

Smoking cessation Encourage spouses to give up Confiscate cigarettes in clinic Change their habits Encourage use of nicotine replacement therapy Smoking cessation service Support groups Hypnosis/acupuncture

Ranking antiplatelet treatment What the trials tell us None Less effective More effective

Ranking antiplatelet treatment What the trials tell us Trialists Collaboration None Aspirin Less effective More effective

Ranking antiplatelet treatment What the trials tell us CAPRIE Trial al Clopidogrel None Aspirin Less effective More effective

Ranking antiplatelet treatment What the trials tell us Aspirin + Clopidogrel al MATCH & CHARISMA Trials Clopidogrel None Aspirin Less effective More effective

Ranking antiplatelet treatment What the trials tell us Aspirin + Dipyridamole ESPS 2 & ESPRIT Trials al None Aspirin Less effective More effective

Ranking antiplatelet treatment What the trials tell us Aspirin + Dipyridamole PROFESS Trial Clopidogrel Less effective More effective

Ranking antiplatelet treatment What the trials tell us Aspirin + Dipyridamole Aspirin + Dipyridamole Aspirin + Clopidogrel al Clopidogrel None Aspirin Less effective More effective

Antiplatelet Drugs Aspirin - treat 100 patients for one year and prevent one stroke Aspirin & Persantin MR marginally better than aspirin alone but more side effects and cost Clopidogrel (PLAVIX) marginally better than aspirin used to much more expensive (x1000) Clopidogrel now much cheaper, so we are tending to use this instead of the asp/dipyridamole combination

Blood pressure reduction Uncertain how soon to start Likely to work but little direct evidence in TIA/ stroke patients Lifestyle changes Benefits of blood pressure lowering per se (we generally aim for target of 130/70) Uncertain optimal regime (depends a bit on what they are already taking) Care needed in haemodynamic TIAs

Cholesterol Reduction Statins if cholesterol >3.5mmol/l

Anticoagulants (Warfarin) Used in patients with Atrial fibrillation Prosthetic heart valves Recent myocardial infarction 80 events avoided per 1000 patient treated

Anticoagulants If Atrial Fibrillation Prosthetic heart valve INR 2-3 if no definite contraindication Cardioversion not of any value Prosthetic heart valve consider combination with aspirin Sinus rhythm consider Heparin in crescendo TIAs

Falls and warfarin Falls: patient with an average risk of stroke from AF (5% per year), it would require the patient to fall roughly 300 times per year for the risks of anticoagulant therapy to outweigh its benefits, in terms of intracranial bleeding (ManSonHing et al) Yet most physicians perceive falls to be a barrier to anticoagulation

Secondary Prevention TIA Ischaemic Risk of recurrence  Sinus rhythm Severe carotid stenosis Ischaemic Carotid surgery Sinus rhythm Atrial fibrillation Antiplatelets Asp + Dip or Clopidogrel Cholesterol  Life style Blood pressure  Anticoagulation Risk of recurrence 

Imaging the blood vessels Carotid and Vertebral artery Ultrasound can show atheroma and occlusions of vessels in neck Transcranial Doppler (TCD) can show flow (or lack of flow) in large intracerebral vessels Magnetic resonance angiography can show extra and intra cranial blood vessels Catheter angiography

Carotid Duplex Carotid duplex is a simple, risk free outpatient procedure.

Stenosis of the origin of the Internal Carotid Artery There is a severe narrowing of the origin of the internal carotid artery. This is likely to be a source of clots (emboli) which can cause TIAs and strokes. In a patient with such a severe narrowing (>80%) who has had recent TIAs or a minor stroke affecting that side of the brain we would recommend an operation to remover the narrowing. This is called a carotid endarterectomy. Randomised trials have shown that it reduces the risk of stroke

Effect of surgery for 50-69% stenosis: time since last event <2 weeks Ipsilateral Carotid Territory Ischaemic Stroke Plus Any Surgical Stroke or Surgical Death Any Stroke or Surgical Death 1 2 3 4 5 6 7 8 9 10 Patients Surgery 158 138 129 117 106 90 72 53 36 18 135 124 112 99 84 66 48 34 16 No surgery 150 130 108 94 70 55 45 33 26 15 . Years from randomisation 0.5 0.6 0.7 0.8 0.9 1.0 Proportion free of event Log-rank = 10.4 P = 0.001 Log-rank = 8.9 P = 0.003 Stroke 2004; 35: 2855-61.

Reduction in the 5-year risk of stroke or death highest if carotid surgery < 2 weeks 70-99% stenosis, highest benefit if surgery < 2 weeks 50-59% stenosis, NO benefit if surgery > 2 weeks after onset Absolute reduction in risk Rothwell, ECST & NASCET investigators, Lancet 2004; 363: 915–24

Carotid Endarterectomy Can be done under local anaesthetic (GALA) 3-5% risk of stroke or death Operate on 5 -10 to prevent one stroke in next 3 years

What is you local surgeons complication rate? Does he continuously audit his results? How does he select cases? Any independent assessment of outcome? Perform 50 carotid endarterectomies with 2 deaths/strokes 4% (95% CI: 0 - 14%)

Summary Careful history critical in making diagnosis Rapid initiation of secondary prevention Antiplatelets, anticoagulants, carotid endarterectomy, statins and antihypertensives are the cornerstone to our treatment