A comprehensive presentation of the Management of Ischaemic Stroke Introduction, Epidemiology, Classification, Pathophysiology, Clinical Presentation, Differentials, Investigation, Management, Prognosis

1. ISCHAEMIC STROKE
DR. NNANNA JEMIE
(BSc, MBBS)

2. OUTLINE
• INTRODUCTION
• EPIDEMIOLOGY
• ANATOMY
• CLASSIFICATION
• RISK FACTORS
• PATHOPHYSIOLOGY
• CLINICAL FEATURES
• DIFFERENTIAL DIAGNOSIS
• INVESTIGATION
• MANAGEMENT
• PROGNOSIS
• CONCLUSION
• REFERENCES

3. INTRODUCTION
• A stroke can be defined as rapidly developing clinical signs of focal (at
times global) disturbance of cerebral function, lasting more than
24hrs or leading to death with no apparent cause other than that of
vascular origin (WHO)
• Generally divided into 2
• Ischaemic
• Haemorrhagic

4. • Ischaemic stroke can be defined as
• Acute focal neurological dysfunction caused by focal infarction at
single or multiple sites of the brain. Evidence of acute infarction may
come either from
• a) symptom duration lasting more than 24 hours, or
• b) neuroimaging or other technique in the clinically relevant area of the brain.
(ICD 11)
• It is an emergency which could, and often is fatal, and as such must
be attended to immediately. Time is brain

6. EPIDEMIOLOGY
• Global incidence of stroke:
• Ischemic = 68%
• Hemorrhagic (ICH and SAH) = 32%
• Worldwide, stroke is the second most common cause of mortality and
the third most common cause of disability
• While the incidence of stroke is decreasing in high-income countries,
the incidence is increasing in low-income countries (the incidence has
more than doubled over the last 4 decades).

7. EPIDEMIOLOGY
• About 15 million people suffer stroke worldwide each year. Of these,
5 million die, and another 5 million are left permanently disabled.
• Someone in the US has a stroke every 40 seconds on average.
• On average in 2016, someone died of stroke every 3 minutes 42
seconds.

8. EPIDEMIOLOGY
• Blacks have a risk of stroke about 1.49 times that of whites. Hispanics
have the lowest risk.
• Men have a higher risk of stroke than women although women have a
higher rate of mortality from stroke.
• One third of strokes occur in persons younger than 65 years

9. EPIDEMIOLOGY
• The overall rate of stroke in Africa is among the world’s highest with
an annual incidence rate of up to 316 per 100,000 population.
• The current prevalence of stroke in Nigeria is 1.14 per 1000 while the
30-day case fatality rate is as high as 40% (2008).

10. EPIDEMIOLOGY
• At UPTH
• Mean age at presentation = 62.62 ± 14.2 years.
• Male to female ratio was 1:1.2.
• Clinically, 67.3% had cerebral infarction (CI), while 27.7% had intracerebral
haemorrhage (ICH)
• Study done in Anambra
• Crude prevalence of stroke in rural Nigeria was 1.63 per 1,000 population.
• Males was 1.99 per 1,000 population.
• Females was 1.28 per 1,000 population

11. Stroke mortality rates per 100,000

12. ANATOMY
• The brain is the most metabolically active organ in the body.
• 2% of total body mass
• 15-20% of resting cardiac output to provide necessary glucose and oxygen for
its metabolism
• Cerebral hemispheres are supplied by
• Anterior Cerebral artery
• Middle Cerebral artery
• Posterior Cerebral artery

13. ANATOMY

14. VASCULAR
TERRITORY
Structures Supplied
Anterior Circulation (Carotid)
Anterior
Cerebral Artery
Cortical branches: medial frontal and parietal lobe
Medial lenticulostriate branches: caudate head, globus pallidus,
anterior limb of internal capsule
Middle Cerebral
Artery
Cortical branches: lateral frontal and parietal lobes, lateral and
anterior temporal lobe
Lateral lenticulostriate branches: globus pallidus and putamen,
internal capsule
Anterior
Choroidal Artery
Optic tracts, medial temporal lobe, ventrolateral thalamus, corona
radiata, posterior limb of the internal capsule

15. Posterior Circulation (Vertebrobasilar)
Posterior
Cerebral Artery
Cortical branches: occipital lobes, medial and posterior temporal and
parietal lobes
Perforating branches: brainstem, posterior thalamus and midbrain
Posterior
Inferior
Cerebellar
Artery
Inferior vermis; posterior and inferior cerebellar hemispheres
Anterior Inferior
Cerebellar
Artery
Anterolateral cerebellum
Superior
Cerebellar Superior vermis; superior cerebellum

16. RISK FACTORS
• Non-Modifiable Risk Factors
• Age: More common in the elderly
• Gender: M > F (mortality > in F)
• Race: Blacks > Whites
• Heredity
Age
Family
History
Genetics

17. Modifiable Risk Factors
• Hypertension
• Diabetes
• Dyslipidaemia
• Metabolic syndrome
• Cardiac Disease (Atrial
Fibrillation, Valvular heart
dx, Cardiomyopathy, MI)
• Overweight and Obesity
• Diet and Nutrition
• Cigarette smoking
• Alcohol
• Physical inactivity
• Illicit drug use
• Hyperhomocysteinemia
• Hypercoagulable state

18. • Dominant modifiable risk factors for stroke in Nigeria in descending order
of population attributable risk (SIREN)
• Hypertension
• Dyslipidaemia
• Regular meat consumption
• Elevated waist-to-hip ratio
• Diabetes
• Low green leafy vegetable consumption
• Stress
• Added salt at the table
• Cardiac disease
• Physical inactivity
• Current cigarette smoking

19. CLASSIFICATION
• Cardioembolic infarct
• Most commonly due to AF and valvular heart disease
• Small-vessel or Lacunar
• Occlusion of the small, perforating arteries of the deep subcortical areas of
the brain.
• Large Artery
• Growth of an atherothrombotic plaque with intraluminal propagation

20. PATHOPHYSIOLOGY
Diagram illustrating the three major
mechanisms that underlie ischemic stroke:
(1) occlusion of an intracranial vessel by an
embolus that arises at a distant site (e.g.,
cardiogenic sources such as atrial fibrillation
or artery-to-artery emboli from carotid
atherosclerotic plaque), often affecting the
large intracranial vessels;
(2) in situ thrombosis of an intracranial
vessel, typically affecting the small
penetrating arteries that arise from the
major intracranial arteries;
(3) hypoperfusion caused by flow-limiting
stenosis of a major extracranial (e.g.,
internal carotid) or intracranial vessel, often
producing “watershed” ischemia

22. • There is a dense central core, surrounded by a less dense zone of
ischaemia (‘penumbra’).
• Neuronal death occurs in the central focus unless perfusion is quickly
restored.
• Cells in the zone of penumbra remain viable for about three hours
(‘therapeutic window’) and can be salvaged by reperfusion or
neuroprotective agents

23. Illustration of the penumbra concept. Infarct core (red): infarcted tissue. Penumbra (orange): salvageable tissue at
risk for infarction in case of persistence vessel occlusion. Oligaemia (yellow): hypoperfused tissue without risk for
infarction.
Cerebral blood flow decreases in direction to the infarct core. Decreased blood flow can be compensated by an
increased oxygen extraction fraction and vasodilation of collateral vessels sufficiently enough in the oligaemia but
not in the penumbra. (Picture: Stroke Centre Bern)

24. PATHOPHYSIOLOGY
• Haemorrhagic Transformation
• Occurs in about 5% of uncomplicated cases, in the absence of fibrinolytic
treatment.
• It is not always associated with neurologic decline.
• Post stroke Cerebral Oedema and Seizures
• Clinically significant cerebral oedema can occur after anterior circulation
ischemic stroke about 10-20% of cases.
• Oedema and herniation are the most common causes of early death in
patients with hemispheric stroke.
• Seizures occur in 2-23% of patients within the first days post ischaemic stroke.
Some patients develop chronic seizure disorders.

25. CLINICAL FEATURES
• History
• Onset
• Affectations (side of the body, limbs, speech, swallowing, coordination etc)
• Severity
• Course
• Precipitating factors (trauma, fever)
• Associations (eg headache, nausea, vomiting, neck stiffness, seizures)
• Previous episodes
• Dominant hand

26. CLINICAL FEATURES
• Identify risk factors including:
• Hypertension
• Diabetes mellitus
• Tobacco use
• High cholesterol
• History of coronary artery disease, coronary artery bypass, or atrial fibrillation
• Recent trauma
• Coagulopathies
• Illicit drug use (especially cocaine)
• Migraines
• Oral contraceptive use

27. CLINICAL FEATURES
• The presentation of the patient usually depends on the site of
occurrence of the stroke.
• Most common manifestations include
• Hemiparesis, monoparesis
• Hemisensory deficits
• Diplopia
• Dysarthria
• Facial droop
• Ataxia
• Aphasia
• Sudden decrease in the level of consciousness

29. CLINICAL FEATURES
• Anterior Cerebral artery
• Contralateral paresis (Legs>Arms>Face)
• Contralateral cortical sensory deficits
• Disinhibition and speech perseveration
• Altered mental status
• Impaired judgment
• Gait apraxia
• Urinary incontinence
• Primitive reflexes (eg, grasping, sucking reflexes)

30. CLINICAL FEATURES
• Middle Cerebral artery
• Contralateral hemiparesis and sensory loss (face > arms > legs)
• Homonymous hemianopsia
• Aphasia (Receptive or Expressive)
• Neglect
• Gaze preference toward the side of the lesion

31. CLINICAL FEATURES
• Posterior Cerebral artery
• Diplopia
• Dizziness
• Dysphagia
• Dysarthria
• Cortical blindness
• Ataxia
• Horner’s syndrome
• Hemiparesis/hemisensory loss contralateral to the CN palsy
• Cerebellar sign

32. CLINICAL FEATURES
• Basilar artery
• Coma
• “Locked-in” syndrome
• Cranial nerve palsies
• Apnoea
• Drop attacks
• Dysphagia
• Dysarthria
• Vertigo
• Crossed weakness and sensory loss affecting the ipsilateral face and
contralateral body

33. CLINICAL FEATURES
• Lacunar Syndromes
• Pure motor hemiparesis
• Pure sensory stroke
• Ataxic hemiparesis
• Dysarthria-clumsy hand syndrome

34. DIFFERENTIAL DIAGNOSES
• Seizures
• Migraine
• Encephalitis
• Gliomas
• Demyelination
• Hypoglycaemia
• Conversion disorder
• Metabolic encephalopathy

35. INVESTIGATION
• CT scan
• Computerised cranial tomography is the single-most important non-
invasive investigation to distinguish an ischaemic infarction and
cerebral haematoma from other conditions simulating strokes
• It also provides an estimate of the extent and location of
supratentorial cerebral infarction, including small (0.5 cm) lacunar
infarct.
• It can also detect surrounding oedema and haemorrhagic infarction.

36. INVESTIGATION
• However, it may not differentiate early (within 1 to 3 hours) ischaemic
lesions from normal tissue.
• Brainstem lacunaes are difficult to detect by conventional CT.
• CT may fail to show small ischemic strokes in the posterior fossa
because of bone artifact; small infarcts on the cortical surface may
also be missed.

37. Pt A: Noncontrast CT demonstrates diffuse hypodensity in the
right lentiform nucleus, with mass effect upon the frontal horn
of the right lateral ventricle. Pt is a 70yr old female with history
of left-sided weakness for several hours duration.
Pt B: Noncontrast CT demonstrates diffuse hypodensity
and sulcal effacement involving the left anterior and
middle cerebral artery territories consistent with acute
infarction. Pt is a 52yr old male with history of worsening
right-sided weakness and aphasia

38. INVESTIGATION
• MRI
• MRI reliably documents the extent and location of infarction in all
areas of the brain, including the posterior fossa and cortical surface
• Diffusion weighted imaging is more sensitive for early brain infarction
than standard MR sequences or CT
• MRI is more expensive and time consuming than CT and less readily
available. Claustrophobia and the logistics of imaging acutely critically
ill patients also limit its application.

39. MRI obtained from Pt A. An axial T2 FLAIR image (left) demonstrates high signal in the lentiform nucleus with
mass effect. The axial diffusion-weighted image (middle) demonstrates high signal in the same area with
corresponding low signal on the apparent diffusion coefficient (ADC) maps, consistent with true restricted
diffusion and an acute infarction.

40. INVESTIGATION
• Vascular Studies
• Carotid ultrasound
• Transcranial Doppler
• Magnetic resonance angiography
• CT angiography
• Conventional angiography
• Haematology & Chemistry
• Full blood count + ESR
• SEUCr
• Fasting lipid profile
• Random blood glucose
• PT/INR

41. INVESTIGATION
• Others
• Chest radiograph
• 2D – Echocardiogram
• Electrocardiography
• Toxicology screening
• Arterial blood gas analysis
• Cardiac biomarkers
• Pregnancy test
• Antinuclear antibody (ANA)
• Rheumatoid factor
• Homocysteine level

42. TREATMENT
• Treatments designed to reverse or lessen the amount of tissue
infarction and improve clinical outcome fall into 6 categories
• Medical support
• IV thrombolysis
• Endovascular revascularization
• Antithrombotic treatment
• Neuroprotection
• Stroke centres and rehabilitation

43. Medical Support
• Immediate goal following an ischaemic stroke is to optimize cerebral
perfusion in the penumbra
• Prevention of common complications of bedridden patients
• Infections
• Pneumonia (NG tube)
• UTI, AKI (Catheter, Input-output chart)
• Skin (Pneumatic mattress, Frequent turning)
• DVT
• Subcut Heparin (LMWH)
• Pneumatic compression stockings

44. Medical Support
• Blood pressure management
• Should be lowered if
• Malignant hypertension
• Concomitant myocardial ischaemia
• BP > 185/110mmHg and
thrombolytic therapy is anticipated
• Routine lowering of blood
pressure has been found to
worsen outcomes
• Fever management
• Antipyretics and surface cooling
• Blood glucose monitoring
• Should be <180mg/dl (10mmol/l)
• Prevention of raised ICP
• Water restriction
• IV Mannitol

45. IV Thrombolysis
• This is done using recombinant tissue plasminogen activator (rtPA)
• It represents the first treatment proven to improve clinical outcomes
(NINDS study – 12% increase in pts with minimal disability, 4%
decrease in mortality)
• Patient must however be eligible (indications and contraindications of
next slide)
• Dependent of location, it is used within the 4.5hrs of onset of stroke
(Europe) and 3hrs of onset (USA and Canada)
• There however is a risk of symptomatic intracranial haemorrhage

46. Administration of Intravenous Recombinant Tissue Plasminogen Activator (rtPA) for Acute
Ischaemic Stroke
INDICATION CONTRAINDICATION
Clinical diagnosis of stroke Sustained BP >185/110mmHg despite treatment
Onset of symptoms to time of drug
administration ≤4.5hrs
Platelets <100,0000; Hct <25%
RBS or FBS <50mg/dl or >400mg/dl
CT scan showing no hemorrhage or edema
of >1/3 of the MCA territory
Use of heparin within 48hrs; Prolonged PTT;
Elevated INR
Age 18 ≥ years Rapidly improving symptoms; Minor stroke
symptoms
Consent by patient or surrogate Prior stroke or head injury within 3months
Prior intracranial haemorrhage
Major surgery preceding 14days
Gastrointestinal bleeding in preceding 21 days
Recent myocardial infarction
Coma or Stupor

47. Administration of rtPA
• IV access with two peripheral IV lines (avoid arterial or central line
placement)
• Review eligibility for rtPA
• Administer 0.9 mg/kg IV (maximum 90 mg) IV as 10% of total dose by
bolus, followed by remainder of total dose over 1hr
• Frequent cuff blood pressure monitoring
• No other antithrombotic treatment for 24hrs
• For decline in neurologic status or uncontrolled blood pressure, stop
infusion, give cryoprecipitate, and reimage brain emergently
• Avoid urethral catheterization for ≥2hrs

48. Revascularisation
• Carotid endarterectomy
• Indicated for stenosis 70-99% after a recent ischaemic event
• Early intervention within 2weeks is more beneficial
• Not recommended for stenosis <50%
• Carotid angioplasty and stenting
• Alternative to carotid endarterectomy if surgery is undesirable, technically
difficult or inaccessible

49. Anti-thrombotic Treatment
• Aspirin is the only antiplatelet agent that has been proven effective
for the acute treatment of ischemic stroke
• Two large trials – IST (19435 patients) and CAST (21106 patients),
found that the use of aspirin within 48hrs of stroke onset reduced
both stroke recurrence risk and mortality minimally
• No benefit has been found in the use of anticoagulants in the primary
treatment of atherothrombotic cerebral ischaemia

50. Neuroprotection
• The concept of providing treatment that prolongs the brain’s
tolerance to ischaemia.
• This is still being researched upon
• Drugs that block the excitatory amino acid pathways have been
shown to protect neurons and glia in animals, but have not been
beneficial in humans
• Hypothermia is also being studied

51. Stroke Centres and Rehabilitation
• Care in stroke units together with rehabilitation services improves
neurologic outcomes and reduces mortality
• Proper rehabilitation includes
• Early physical, occupational and speech therapy
• The goal of rehabilitation is to
• return the patient home
• maximize recovery by providing a safe, progressive regimen suited to the
individual patient

52. Primary Prevention
• Hypertension:
• Treat if BP >140/90mmHg
• Diabetes:
• Tight glycaemic control
• Hyperlipidaemia:
• LDL <2.6mg/dl (in high risk groups)
• LDL <4.2mg/dl (if no risk factor)
• Aspirin therapy
• Smoking cessation

53. Secondary Prevention
• Involves
• Lifestyle modification
• Control of modifiable risk factors and Treatment of aetiologies
• Antihypertensive treatment
• ACEIs
• Thiazide diuretics
• Lipid lowering
• Atorvastatin (40mg dly)

54. Secondary Prevention
• Good glycaemic control
• Use of antiplatelets
• Aspirin (75mg – 350 mg dly)
• Clopidogrel (75mg dly)
• Use of anticoagulants
• Dabigatran (150mg dly)
• Warfarin (1 - 5mg dly)*

55. Secondary Prevention
• Stop oral contraceptives and hormone replacement therapy
• Cessation of tobacco smoking

56. PROGNOSIS
• In subjects who survive stroke, some degree of recovery is the rule
• Chances of significant recovery are remote when no improvement is noted
within first 6 weeks to 8 weeks.
• About 20% to 25% of the patients with massive cerebral infarction and
brain swelling die during the acute phase.
• Here, old age, presence of severe neurological deficit with coma and
pyrexia, intercurrent infections, poorly controlled hypertension, diabetic
states and basilar artery thrombosis are of grave prognostic significance.

57. PROGNOSIS
• Recurrent episodes are frequent but there is no way to predict the
same in a given subject. However, control of ‘risk-factors’ is beneficial.
• Early identification and prompt treatment is key in saving the life of
the patient.

58. CONCLUSION
• Strokes are an emergency (with rising incidence in LMICs), which if
not attended to immediately can be fatal.
• Imaging on presentation is greatly advised.
• Medical support is very important.
• Early commencement of rehabilitation (esp Physiotherapy) is very
important for the recovery of the patient.
• Communication with family members on the nature of the disease
and the prognosis (to allay fears and aid recovery) is necessary.

59. REFERENCES
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Stroke in South Ethiopia. Journal of Neurological Science. 355:138-42.
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Southeastern Nigeria.
• Eric SD (2018). Stroke in the 21st Century: A Snapshot of the Burden,
Epidemiology, and Quality of Life. Stroke Research and Treatment.
• Kasper D et al (2015). Harrison’s Principles of Internal Medicine 19th
Edition. New York : McGraw Hill
• Munjal YP et al (2012). API Textbook of Medicine 9th Edition. Mumbai
Jaypee Brothers

60. REFERENCES
• MacKay J, Mensah GA. World Health Organization. Global Burden of Stroke. The
Atlas of Heart Disease and Stroke.
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World Neurosurgery. 76:S85-90.
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152. https://doi.org/10.1258/td.2008.080285
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and a glimpse into the future. Cardiovascular Journal of Africa 26(2)
• Owolabi MO, Sarfo F, Akinyemi R, et al. Dominant modifiable risk factors for
stroke in Ghana and Nigeria (SIREN): a case-control study. Lancet Glob Health.
2018;6(4):e436–e446.

61. REFERENCES
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