This document provides an outline on thromboembolic stroke. It begins with definitions and classifications of stroke, including the WHO and TOAST classifications. It then discusses the epidemiology, risk factors, pathophysiology, clinical presentation and diagnosis of stroke. It also covers management and prevention, noting that stroke is a major cause of death and disability worldwide, especially in sub-Saharan Africa. Modifiable risk factors include hypertension, diabetes, atrial fibrillation, hyperlipidemia and smoking.

1. THROMBOEMBOLIC STROKE
DR. IBEANU CHARLES

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

3. “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)

4. 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

5. 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

6. 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

7. CLASSIFICATION

8. 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

9. 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
SUBTYPES

10. 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

11. A. Thrombosis
Large extracranial vessels
• Atherosclerosis
• Dissection
• Takayasu arteritis
• Giant cell arteritis
• Fibromuscular dysplasia
Small vessel disease
• Lipohyalinosis ( due to hypertension) and fibrinoid
degeneration
ETIOLOGY

12. 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

14. 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

15. 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).

16. Effects of decreased cerebral blood flow
on vital brain functions

17. • 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

18. • 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

19. • 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

20. • 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

21. • 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

22. Estimates of Long-term Risk of Stroke
After Ischemic Stroke or TIA
Time
After 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

23. A Age ≥60 years 1 point
B Blood pressure
SBP >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

24. ABCD2 Score Level of Risk
2-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

25. 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

26. 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
PRESENTATION
Symptoms and signs

27. • 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

28. • 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

29. 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

30. • ACUTE phase
– Ambulance
– Emergency room
– Neuro-ICU
– Stroke Unit
• SUBACUTE phase
– Stroke Care ward
• CHRONIC phase
– Clinic
– Rehabilitation
– Domiciliary
MANAGEMENT

31. • 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

32. • 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.

33. • 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.

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

35. • 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.

36. • 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.

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

38. • F: facial deviation
• A: arm or leg weakness
• S: slurred speech
• T: timing
COMMUNITY IDENTIFICATION

39. THANK YOU!
Спасибо за внимание