Stroke Therapeutics

8/6/2019 Stroke Therapeutics

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Stroke

Clinical syndrome

Characteristics

y Rapidly developing clinical symptoms

y Signs of focal (or global) loss of cerebral function

y Symptoms lasting > 24h (or leading to death)

y No apparent cause other than vascular origin

Clinical Features

Anterior (carotid) artery circulationPosterior (vertebrobasilar) artery

circulation

Middle cerebral artery

y Aphasia (dominant hemisphere)y Hemiparesis/ plegia

y Hemisensory loss/ disturbance

y Homonymous hemianopia

y Parietal lobe dysfunction

(eg. astereognosis,

agraphaesthesia, impaired 2-

point)

y Discrimination, sensory & visual

inattention, left-right

dissociation, acalculia

Anterior cerebral artery

y Weakness of lower limb more

than upper limb

Homonymous hemianopia

Cortical blindnessAtaxia

Dizziness, vertigo

Dysarthria

Diplopia

Dysphagia

Horners syndrome

Hemiparesis/ hemisensory loss

(contralateral to cranial nerve palsy)

Cerebellar signs

Types of Stroke

Ischaemic Haemorrhagic

Majority (85%) ischemic origin

Main phenomena

y Platelet activation cascade

(adhesion, activation,

aggregation)

y Blood coagulation cascade

(fibrin formation)

Smaller percentage (15%)

Types

Intracranial

haemorrhage

(ICH)

Subarachnoid

haemorrhage

(SAH)

Hypertension Aneurysm

AVM

Early changes

Ischaemic coreIschaemic

penumbra

Region of brain

without

significant

blood supply

Regions of

decreased or

marginal

perfusion

Dies within

minutes

May remain

viable for a few

hours

Neuronal

tissue

preservation

possible

Risk FactorsUnmodifiable Modifiable

Age

Sex

Ethnicity

Family history

Hypertension

Diabetes

Coronary heart disease

Atrial fibrillation

Hyperlipidaemia

Smoking

Obesity

Previous stroke

Sedentary life style

Dietary salt, alcohol

Prognosis

Depends on

y Type

y Size

y Location

Higher mortality in haemorrhagic stroke

Poor prognosis

y Brainstem infarct

y Large hemispheric infarct

y Cardio embolic stroke



Ischaemic Stroke Therapeutics

Fibrinolytics Antiplatelets Anticoagulants

rt-PA

Recombinant tissue-type plasminogen activator

Treatment of ischaemic stroke

(streptokinase not recommended)

Indication - Acute treatment of ischaemic stroke

Reperfuse ischaemic brain & salvage penumbra area

IV rt-PA within 3h of onset

(can likelihood of return to normal by 30%)

t-PA promote formation of plasmin from plasminogen

(enzyme that digests fibrin)

Aspirin (COX Inhibitor)

Indication Acute treatment of ischaemic stroke

y Recommended to start within 48h of stroke

onset

y Not recommended within 24h of fibrinolytic

administration

Prevention

Primary (1°) Secondary (2°)

Only useful in

females > 65 y/o

Given to all patients of

stroke to prevent

further stroke

Aspirin inhibit platelet aggregation

(by inhibiting synthesis of TxA2)

(irreversibly inhibiting COX enzyme)

Heparin, Warfarin

Indications

y Not indicated in acute treatment of ischaemic

stroke

y Followingcardio embolic stroke

Need to monitor closely for haemorrhage

Anticoagulants

Heparin (UHF) Warfarin

Given in high risk

patient

Given after patient has

stabilised

Clopidogrel/ Ticlopidine (ADP Inhibitors)

Indications - Secondary (2°) prevention

y Alternative to aspirin (eg. intolerant)

y Double therapy

(aspirin + clopidogrel/ ticlopidine)

indicated only in selected high risk patients

if benefit outweighs risk

Treatment Guidelines Prevention

Primary (1°) Secondary (2°)

Hypertension

DiabetesMellitus

Hyperlipidaemia

Smoking

Aspirin therapy

Post menopausal HRT

Alcohol

Strategies used after a stroke

(prevent recurrence)

Risk for recurrent vascular event

(after stroke or TIA)

y 5% per year for stroke

y 3% per year for myocardial

infarction

Antiplatelets

Aspirin

Clopidogrel

Ticlopidine

Anti-hypertensive treatment

Lipid lowering

Diabetic controlCigarette smoking

Cardioembolism

Account for up to 20% of ischaemic stroke

Associated with poor prognosis

Common source

y Intra-atrial emboli

y Intra-ventricular emboli

Causes

y Atrial fibrillation (50%)

y Prosthetic heart valves

y Rheumatic valvular heart disease

y Recent MI

y Non thrombotic endocarditis, myxoma

Treatment

y Aspiriny Warfarin

y Heparin (unfractionated)

y Anticoagulation

Revascularization

Carotid endarterectomy (CEA) Angioplasty/ stenting (CAS)



Management of Haemorrhagic Stroke

Depend on

y Underlying cause of haemorrhage

y Extent of damage

Repair of cause of bleeding surgical removal (large clots)

Symptomatic treatment

y Intracranial pressure (ICP)

Haemorrhagic stroke is often associated with symptoms of ICP

y Blood pressure

y Seizures

Location

Subarachnoid Intracerebral Cerebellar Lobar

Neurosurgical

intervention

Management of

ICP

Surgical

evacuation(good outcome)

Neurosurgical

evacuationNimodipine

(CCB)

Neurosurgical

decompression

Management

Mannitol Antihypertensives Factor VIIa

Osmotic diuretic If BP not controlled Limit bleeding &

hematoma formation

if given early (< 4h)Effective in acutely

reducing raised ICP

Risk of

thromboemoblism

Removal of anticoagulants/

antithromboticsOthers

Haemorrhagic stroke results from

administration of anticoagulants/

antithrombotics

Pain relievers

Antianxiety medications

Anticonvulsants for seizures

Documents

Stroke Therapeutics