THROMBOEMBOLIC STROKEDR. IBEANU CHARLES

• DEFINITION• EPIDEMIOLOGY / BURDEN• CLASSIFICATION / ETIOLOGY• PATHOPHYSIOLOGY• RISK FACTORS• CLINICAL PRESENTATION• DIAGNOSIS• MANAGEMENT• PREVENTION / COMMUNITY IDENTIFICATION

OUTLINE

“Rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than of vascular origin”

By this definition, TIA, which lasts <24 hours, and patients with stroke symptoms caused by subdural hemorrhage, tumors, poisoning or trauma are excluded.

DEFINITION(By WHO)

EPIDEMIOLOGY

• Annually, 15 million worldwide suffer a stroke- 5 million die and 5 million are permanently disabled

• WHO estimates a stroke occurs every 5 seconds• Stroke related disability is the sixth most common cause

of reduced DALYs• Accounts for 10% of all deaths worldwide

BURDEN OF STROKE

Stroke has assumed an epidemic proportion in developing countries especially sub-Saharan Africa (SSA)

World Stroke Congress declared stroke as an epidemic and called WHO and WSO combined efforts

The sub-Saharan Africa bears the brunt:

Two-thirds of cases

High case fatality

Ischemic Stroke —  three subtypes:• Thrombosis : In situ obstruction of an artery. • Embolism : Particles of debris originating elsewhere that

block arterial access to a particular brain region.• Systemic hypoperfusion : More general circulatory problem,

manifesting itself in the brain and perhaps other organs.

Hemorrhagic Stroke due to intracerebral hemorrhage or subarachnoid hemorrhage

Data compiled by AHA show that strokes due to ischemia, intracerebral hemorrhage and subarachnoid hemorrhage are 87%, 10%, and 3 %respectively

CLASSIFICATION

CLASSIFICATION

TOAST Classification [9]

1. Large-artery atherosclerosis (embolus/thrombosis)*

2. Cardioembolism (high-risk/medium-risk)*

3. Small-vessel occlusion (lacune)*

4. Stroke of other determined etiology*

5. Stroke of undetermined etiology

a. Two or more causes identified

b. Negative evaluation

c. Incomplete evaluation*Possible or probable depending on results of ancillary studies.

STROKE SUBTYPES

Stroke Data Bank Subtype (NINDS) Classification [10]

Derived from the Harvard Stroke Registry classification, the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank recognised -

1. Atherothrombosis

2. Tandem arterial pathology

3. Cardiac Embolism

4. Lacune

5. Unusual Cause

6. Infarction of undetermined cause

7. Parenchymatous haemorrhage

8. Subarachnoid Hemorrhage

SUBTYPES

Based on symptoms -

1.Total anterior circulation stroke (TAC)

2. Partial anterior circulation stroke (PAC)

3.Lacunar stroke (LAC)

4. Posterior circulation stroke (POC)

The type of stroke is then coded by adding a final letter to the above:• I – for infarct (e.g. TACI)• H – for haemorrhage (e.g. TACH)• S – for syndrome; intermediate pathogenesis, prior to imaging (e.g.

TACS) These four entities predict the extent of the stroke, the area of the brain affected, the

underlying cause, and the prognosis.

OXFORD CLASSIFICATION

A. ThrombosisLarge extracranial vessels

• Atherosclerosis• Dissection• Takayasu arteritis• Giant cell arteritis• Fibromuscular dysplasia

Small vessel disease • Lipohyalinosis ( due to hypertension) and fibrinoid

degeneration

ETIOLOGY

1. Cardiac sources definite - antithrombotic therapy generally used

Left atrial thrombus

Left ventricular thrombus

Atrial fibrillation

Sustained atrial flutter

Recent myocardial infarction (within 1 month)

Rheumatic mitral or aortic valve disease

Bioprosthetic and mechanical heart valve

Chronic myocardial infarction with ejection fraction <28 percent

Symptomatic heart failure with ejection fraction <30 percent

Dilated cardiomyopathy

B.Cardioaortic embolic stroke

2. Cardiac sources possible

Mitral annular calcification

Patent foramen ovale

Atrial septal aneurysm

Atrial septal aneurysm with patent foramen ovale

Left ventricular aneurysm without thrombus

Isolated left atrial smoke (no mitral stenosis or atrial fibrillation)

Mitral valve strands

3. Cardiac sources definite - anticoagulation hazardous

Bacterial endocarditis

Atrial myxoma

4. Ascending aortic atheromatous disease

Obstruction caused by development of fatty deposits lining the vessel walls. It mainly affects the vessels of the brain and heart. Thrombosis refers to thrombus usually blood clot that develops at clogged part of the vessel usually heart & large arteries of upper chest & neck. Embolism refers generally to blood clot that breaks loose enter the blood stream & travel through the brain blood vessel until it reaches the vessel too small to let it pass. Another cause is an irregular heart beat known as atrial fibrillation where clot can form in the heart, dislodge & travel to the brain.

Silent stroke is a brain injury likely caused by blood clot interrupting blood flow in the brain. It’s a risk factor for future strokes which could lead to progressive brain damage`

PATHOPHYSIOLOGY

Ischemic stroke reduces energy availability and therefore membrane ionic primes fail rapidly. The increase in extracellular potassium can reach levels sufficient to release excitotoxic neurotransmitters (e.g., glutamate and aspartate) to stimulate sodium/calcium channels coupled to glutamate receptors that can facilitate developing cytotoxic edema. The significant influx of calcium through calcium channels increase free cytosolic calcium that causes mitochondrial calcium overload, cessation of already compromised ATP production, and extensive breakdown of cellular phospholipids, proteins, and nucleic acids owing to Ca2+ activation of phospholipases, proteases, and endonucleases. Free radicals are produced in the process and contribute to membrane lipid peroxidation, protein and nuclear DNA toxic changes, and cellular injury (i.e., necrosis and/or apoptosis).

Effects of decreased cerebral blood flow on vital brain functions

• Family history of stroke: non-modifiable• Male gender: non-modifiable• History of TIAs: non-modifiable

– Warning events– Risk 1-2% at 1 wk; 2-4% at 1 mth– Canadian study: 6-7% at 30days; 9.5% at 90days;

stroke resulting in death/yr 21.8%– OXVASC 8.6% in 1 wk, 11.5% in 1mth,17.3% in

3mths– Prognosis

• Age>60; symptom duration; diabetes; weakness; speech impairment

RISK FACTORS

• Homocystinuria: non-modifiable– Recessive/dominant enzyme def– Most common recessive cystathione β synthase on chrm 21q22.3– Premature atherosclerosis, ectopia lentis, mental retardation, skeletal deformities,

osteoporosis, recurrent venous thrombosis

• Hypertrophic cardiomyopathy: non-modifiable• Hereditary hyperlipidemias: non-modifiable

– Types II & IV– Alpha lipoproteinemia– Tangier’s disease; familial hypercholesterolemia

• Mitochondrial encephalomyopathy (MELAS): non-modifiable

• Carotid stenosis stenting, endarterectomy, angioplasty

• Aortic arch atheroma• Arterial dissection

– Vaso-occlusive disease (Moyamoya)– Aneurysmata– Vascular fistulae– Type IV Ehler-Danlos (type III collagen deficit; autosomal dominant)

• Carotid-carvenous fistulae• Intracranial aneurysmata• Arterial dissection

• Marfans syndrome: non-modifiable– Autosomal dominant; defect in fibrillin type 1 or TGFβ receptor type II

gene (chrm 15, 3)– Characteristic habitus– Aortic dissection & carotid arteries– Intra/extracranial aneurysmata

• Pseudoxanthoma elasticum: non-modifiable• Autosomal dominant/recessive• Elastic fibers of skin, eye,vasculature• Occlusive lesions of carotid/cervical arteries• Moyamoya• Intracranial aneurysmata• Arterial dissection rarely

• Neurofibromatosis type I– Autosomal dominant; mutation in tumor suppressor gene, neurofibromin– Stenosis/occlusion of supraclinoid ICA with moyamoya– AV fistulae, aneurysmata

• Osteogenesis imperfecta– autosomal dominant, mutations in the α1 or α2 chain of type 1 collagen– Dissection of cerebral vessels

• Fabry’s disease– X-linked; def α-galactosidase; accumulation of glycosphingolipids in vascular

endothelium– Ischemic stroke 2/3 of infarcts in vertebro-basilar region– Large vessel disease – dotrichoectasia – thrombosis– Widespread small vessel disease; asymptomatic strokes– Cardio-embolic strokes (premature MI or valvular involvement)– Age 21-30– Angiokeratomata, painful acroparaesthesia, renal failure

Estimates of Long-term Risk of Stroke After Ischemic Stroke or TIA

TimeAfter TIA1

(%)

After Stroke2

(%)

30 days 4–8 3–10

1 year 12–13 10–14

5 years 24–29 25–40

Percentage of Patients Experiencing Stroke

A Age ≥60 years 1 point

B Blood pressureSBP >140 mm Hg or DBP ≥90 mm Hg

1 point

C Clinical features Unilateral weakness 2 points

Speech disturbance without weakness

1 point

D Duration of symptoms ≥60 minutes 2 points

10–59 minutes 1 point

D Diabetes Diabetes 1 point

Predicting Risk of Stroke After TIA:

ABCD2 Score for 2- or 7-Day Risk of Stroke

ABCD2 Score Level of Risk2-Day Stroke Risk

(%)

6–7 High 8.1

4–5 Moderate 4.1

0–3 Low 1.0

ABCD2 Is Predictive of 2-Day Risk of Stroke in Patients with TIA

Modifiable risk factors

• Elevated blood pressure

• Diabetes mellitus

• Atrial fibrillation

• Carotid artery disease

• Hyperlipidaemia

• Cigarette smoking

• Obesity

• High alcohol consumption

Summary of risk factors for stroke

Paraplegia or paresis (hemi, mono, quadri)

Hemisensory deficits

Mono or binocular visual loss

Visual field deficits

Diplopia

Dysathria

Facial drooping

Ataxia

Vertigo

Aphasia

Sudden loss of consciousness

PRESENTATIONSymptoms and signs

• Proper history taking• Vital signs:Blood pressure•  MAP usually elevated in acute stroke. • Represents response to maintain brain perfusion. • Decision to treat requires balance between severe increases in blood pressure, and decline in neurologic functioning with

decreased BP.

Breathing• Raised ICP (ICH/vertebrobasilar ischemia/ bihemispheric ischemia) - decreased respiratory drive /muscular airway

obstruction.• Hypoventilation (increase in PCO2) - cerebral vasodilation -further elevates ICP.• Intubation- to restore adequate ventilation and protect airway.• Especially in vomiting with increased ICP

Fever • Worsens brain ischemia • Normothermia should be maintained.

DIAGNOSIS

• Absent pulses (inferior extremity, radial, or carotid) - favours atherosclerosis with thrombosis

• Sudden onset of cold, blue limb- favours embolism.• Occlusion of common carotid artery in the neck with bruit -occlusive extra

cranial disease• Temporal arteritis- temporal arteries irregular and with dilatation, tender,

pulseless• Cardiac findings(especially atrial fibrillation, murmurs, cardiac

enlargement) - favour cardiac-origin embolism.• Carotid artery occlusion –iris speckled, ipsilateral pupil dilated and poorly

reactive, retinal ischemia•  Fundus - cholesterol crystal, white platelet-fibrin, or red clot emboli.

PHYSICAL EXAMINATION

Transcranial Doppler US• Echocardiography (cardiogenic embolism suspicion)• ECG• CXR• Single-proton emission CT (SPECT) • Conventional angiography (Gold standard for CVD)• Conventional MRI, MRA• noncontrast CT scanning, CTA, CT perfusion scanning• Blood tests (FBC, coagulation studies, cardiac biomarkers)

INVESTIGATION

• ACUTE phase– Ambulance– Emergency room– Neuro-ICU– Stroke Unit

• SUBACUTE phase– Stroke Care ward

• CHRONIC phase– Clinic– Rehabilitation – Domiciliary

MANAGEMENT

• Fibrinolytic therapy: Fibrinolytics restore cerebral blood flow. Recombinant tissue-type plasminogen activator (rt-PA) attempt to establish revascularization so that cells in the penumbra can be rescued before irreversible injury occurs. Should be used 3 hours of onset of stroke & CT scan ruled out hemorrhagic stroke. Not to be used if >80yrs, Hx of stroke or DM, SBP/DBP > 185/110mmHg, head trauma, ICH, INR>1.7, Plt<100,000/µL , Blood glucose< 50mg/dL, Major surgery < 14days etc. E.g: Streptokinase, Urokinase, Alteplase

• Antiplatelet Agent: AHA/ASA guidelines recommend giving aspirin, 325mg orally within 24-48 hours. The benefit of aspirin is modest but statistically significant and appears principally to involve the reduction of recent stroke

• Statins have both neuroprotective as well as neurorestorative effects. Statins improve endothelial function and have anticoagulant, antiinflammatory, and antithrombogenic properties, all of which may foster neuroprotective effects. The antiinflammatory effects of statins suggest that these agents may also be effective when used in combination with thrombolytic therapies, such as with recombinant tissue plasminogen activator, possibly extending the therapeutic window and reducing hemorrhagic transformation.

• Blood pressure control: BP should not be crashed because it is needed for brain perfusion. It should be decreased if the MAP < 140mmHg after 1-2week but if MAP > 140mmHg there should be gradual reduction in the blood pressure. Early lowering of blood pressure with low dose labetalol and Lisinopril slightly improved outcome and did not increase serious adverse events.

• Cerebral edema control: In emergency situations IV 20% mannitol 350ml (10-15mins) then 150ml 6hrly alternate with N/S 500ml 4hrly.

• Anticoagulation and prophylaxis: Patients with embolic stroke who have another indication for anticoagulation (eg, atrial fibrillation) may be placed on anticoagulation therapy nonemergently, with the goal of preventing further embolic disease; however, the potential benefits of that intervention must be weighed against the risk of hemorrhagic transformation. Immobilized stroke patients in particular are at increased risk of developing deep venous thrombosis (DVT) and should receive early efforts to reduce the occurrence of DVT. The use of low-dose, subcutaneous unfractionated or low–molecular-weight heparin may be appropriate in these cases.

• Mechanical thromboectomy:

Mechanical clot disruption is an alternative for patients in whom fibrinolysis is ineffective or contraindicated. Specially trained doctors try removing the blood clot by sending a catheter to the site of the blocked blood vessel in the brain. Sometimes these procedures involve tPA being administered directly into the blood clot (called intra-arterial treatment) to help dissolve the blockage.

• A: Alcohol/smoking • B: Blood pressure• C: Cholesterol• D: Diet/drugs• E: Exercise

PREVENTION

• F: facial deviation• A: arm or leg weakness• S: slurred speech• T: timing

COMMUNITY IDENTIFICATION

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