- Ischemic stroke is the second leading cause of death worldwide and is caused by occlusion of cerebral blood vessels leading to brain tissue death. - Risk factors include atrial fibrillation, hypertension, diabetes, and smoking. - Treatment involves stabilizing the patient, administering fibrinolytic drugs like rtPA within 4.5 hours, or performing a mechanical thrombectomy for large vessel occlusions. Long term management focuses on prevention of recurrence through antithrombotic drugs and controlling risk factors.

1. Ischemic stroke
Dr Baba H S

2. Outline
• INTRODUCTION
• EPIDEMIOLOGY
• CLASSIFICATION
• ETIOLOGY/RISK FACTORS
• PATHOPHYSIOLOGY
• CLINICAL MANIFESTATION
• INVESTIGATION
• TREATMENT
• COMPLICATIONS
• PREVENTION
• REFERENCES

3. Introduction
• Stroke is defined as a syndrome of rapid onset neurological deficit of
vascular origin caused by focal cerebral, spinal or retinal infarction or
hemorrhage
• TIA is defined as a transient episode of neurological dysfunction
caused by focal brain, spinal cord or retinal ischemia without
evidence of acute ischemia (AHA/ASA 2009)

4. • Stroke is the second leading cause of death worldwide, with
6.2million dying from stroke in 2015
• Stroke is a significant economic, social and medical problem
worldwide
• Stroke has grown in incidence worldwide , however it is declining
among the affluent and rising among those with less access to
medical care

5. Epidemiology
• 5th commonest cause of death, if considered separately from CVD
• Leading cause of disability worldwide
• In the US, annual incidence 795,000
• Prevalence increases with age
• Lifetime risk higher in women
• In Nigeria, prevalence is 1.14/1000, 30 day case fatality rate 40%
(Kolawole W. H)

6. • Stroke registry in Ibadan gave the annual incidence of stroke in
Nigerians as 26 per 100,000 populations
• At LASUTH stroke was the commonest cause of neurological
admissions
• In Nigeria cerebral ischemia accounted for 64%, ICH for 19% and SAH
for 6% of all strokes
• A cross sectional study between Jan 2010 and July 2013 in NHA
showed 62.5% had ischemic stroke while ICH 30.5% and SAH was
2.9%.[Nura H.A et-al]

7. • Stroke is classified into two major types
• Brain ischemia due to thrombosis, embolism, or systemic
hypoperfusion.
• Brain hemorrhage due to intracerebral hemorrhage (ICH) or
subarachnoid hemorrhage (SAH).

8. • Ischemic stroke represents a variety of conditions in which blood flow
to part or all of the brain is reduced resulting in tissue damage
• Ischemic stroke can be classified clinically using the TOAST
classification and Bamford classification

11. Watershed infarcts
• Defined as a brain ischemia localized to the vulnerable border zones
between the tissues supplied by ACA, MCA & PCA.
• The actual blockage site can be located far away from the infarcts.
• Comprise approximately 10% of all ischemic stroke cases
• particularly susceptible to infarction from global ischemia due to
hypoperfusion
• Memory loss, intellectual impairment, motor deficits
• Hypoxic ischemic encephalopathy due to prolonged hypoperfusion

12. Risk factors

13. Anatomy
• -Brain represents 2% body
mass
• -Requires 15-20% total cardiac
output to function
• - Blood supply through the
internal carotid artery &
vertebrobasilar artery

17. Etiology
• Thrombosis: lacunar stroke, large-vessel thrombosis.
• Embolic occlusion : artery-to-artery, cardioembolic (atrial fibrillation, mural
thrombus, myocardial infarction, DCM, Mitral stenosis), paradoxical embolus
• Drugs: cocaine, amphetamine, LSD, heroin
• Hypercoagulable disorders: Protein C, S deficiency, SC anaemia, TTP, DIC,
nephrotic syndrome
• Fibromuscular dysplasia
• Vasculitis, SLE
• Fat/air embolus
• Moyamoya disease
• Eclampsia

21. Cardiac causes
• Atrial Fibrillation
• Prosthetic valves
• Acute myocardial infarction
• Paradoxical systemic emboli
(PFO, ASD, VSD)
• SBE/ IE
• Atrial myxoma

22. Cerebral autoregulation & cerebral perfusion
pressure
• The brain is able to autoregulate its blood flow within a mean arterial
pressure of 60-150mmhg (cerebral autoregulation)
• Beyond this pressure the brain is unable to compensate for changes
in perfusion pressure
• Cerebral auto regulation is impaired during ischemic stroke.
• In hypertensive individuals, autoregulation is adapted to occur in high
arterial pressure. Sudden reduction of BP to normal could exacerbate
Autoregulation derangement leading to further CBF reduction.

23. pathophysiology
• Acute occlusion of an intracranial vessel leads to a decrease in blood
flow to the brain region it supplies
• Reduction in cerebral blood flow to zero causes brain tissue death
within 4-10mins
• Blood flow <16-18ml/100g tissue/min leads to infarction within an
hour
• <20ml/100mg tissue/min  ischemia without infarction unless
prolonged (hours-days)

24. • A TIA results when blood flow is restored to ischemic tissue before
significant infarction develops.
• Ischemic core is an affected area where blood flow is
<10ml/100g/min
• Ischemic penumbra, blood flow <25ml/100g/min
-area surrounding the ischemic core
-neurons are non functional
-structurally normal
-target of revascularization

25. • Infarction occurs via 2 pathways
1. Necrotic pathway
2. Apoptotic pathway

26. Ischemic Cascade

27. • With decreasing cerebral blood flow the following occurs:
• Protein synthesis is initially inhibited and completely ceases
• Transient increase in glucose utilization then it drops dramatically
with conversion to anaerobic glycolysis
• There's accumulation of lactic acid with tissue acidosis
• Neuronal electrical failure and failure of membrane ion hemostasis

28. Brain ischemia initiates a cascade of events that eventually lead to cell
death, including:
• Depletion of adenosine triphosphate (ATP)
• Changes in ionic concentrations of sodium, potassium, and calcium
Increased lactate, acidosis
• Accumulation of oxygen free radicals
• Activation of proteolytic processes.
• Intracellular accumulation of water leading to cytotoxic edema

29. • Ischemia also directly results in dysfunction of the cerebral
vasculature with breakdown of the blood-brain barrier
• Influx of proteins and water into the extracellular space leading to
vasogenic edema.
• Extravasation of peripheral blood from disrupted blood brain barrier
can also occur hemorrhagic transformation

30. Clinical presentation
• Common signs and symptoms :
• Hemiparesis, monoparesis or quadriparesis
• Hemisensory deficits
• Monocular or binocular visual loss, visual field deficits, diplopia
• Dysarthria, aphasia, facial droop
• Ataxia, Vertigo
• Sudden decrease in level of consciousness

31. Management
• Focused hx and examination to establish the lesion, localize region of
brain dysfunction and identify risk factors.
• Airway, breathing and circulation
• Vital signs
• Head and neck exam
• Major organ system examination: CVS, neurologic
• National Institute of Health Stroke Score: NIHSS

32. Investigations
• Emergent Non contrast brain CT
• CT perfusion, CT angiography
• Brain MRI: structural details and show early cerebral edema
• MRI angiography
• Carotid Doppler
• ECG, ECHO

33. • Blood glucose, HbA1C
• FBC, ESR, clotting profile
• Lipid profile
• Serology
• Toxicology screen
• Genetics

34. Investigations
• Non contrast CT scan
-immediate
- Hyperdense middle
cerebral artery sign
-aka DOT sign

35. • Hyperacute (0-24hours)
-loss of grey white matter
differentiation
-cortical hypodensity
-sulcal effacement

36. • Acute phase
-mass effect
• Chronic phase
-gliosis
-hypodensity with negative mass effect
-cortical mineralization (hyperdense)

38. Treatment
• AIMS:
-redeem the ischemic penumbra
-achieve timely recanalization of occluded artery & reperfusion of
ischemic tissue
-optimize collateral flow
-apply principles of acute stroke care
-avoid secondary brain injury

39. • ABC: airway, breathing, circulation
• Stabilize the patient as necessary
• Complete initial evaluation and assessment all within 60 mins of
patient arrival
• Address comorbidities: antipyretics, oxygen supplementation, IVF ,
vasopressor therapy
• Blood glucose control. : maintain blood glucose level between 140-
180mg/dl (7.7-10mmol/L)

40. Blood pressure control
• For patients who are not candidates for fibrinolytic therapy, current
guidelines recommend permitting moderate hypertension in most
patients with acute ischemic stroke.
• The exceptions would be patients who have active comorbidities (eg,
aortic dissection, acute myocardial infarction [MI],
• Acute antihypertensive therapy is typically indicated when blood
pressure is >220/120 mm Hg,(ASA 2013)
• For those who have received IV thrombectomy blood pressure should
be maintained

41. Fibrinolytic therapy
• IV thrombolysis with rtPA is proven to be effective in improving functional
outcomes after an ischemic stroke up to 4.5 hours after symptom onset
• Fibrinolytic therapy with alteplase (rt-PA).
• Indications for administration of rtPA for AIS
– Clinical diagnosis of stroke
– Onset of symptoms to time of drug administration ≤ 4.5 h
– CT scan showing no hemorrhage or edema of >1/3 of the MCA territory
– Age ≥ 18 years
-persisting neurological deficit

43. • Endovascular therapy with mechanical thrombectomy :
• for patients in whom fibrinolysis is ineffective or contraindicated.
Within 6-16hrs post event
• 4 devices have been approved :
1. Merci retriever
2. Penumbra system
3. Solitaire FR Revascularization Device
4. Trevo

45. Antithrombotic therapy
• AHA/ASA recommend giving aspirin 325mg PO within 24-48hrs of
ischemic stroke onset
• Aspirin therapy reduces the risk of stroke recurrence within 14 days (
International Stroke Trial )
• Aspirin treatment started within 48 hrs of onset of AIS and continued
for up to 4 weeks reduced mortality to 3.3% (CAST)

46. • DAPT -is recommended in the short term and only for specific
patients: those with early arriving minor stroke and high-risk TIA or
severe symptomatic stenosis
• Treatment with DAT (aspirin + clopidogrel) started within 24hrs of
onset and continued up to 21 days is effective in reducing ASI
recurrence within 90 days.

47. Anticoagulation
• Atrial Fibrillation- 2 weeks after AF
• Arterial dissection- immediately due to high risk of re stroke
• Venous sinus/ cortical vein thrombosis
- Warfarin
- DOAC: thrombin inhibitors- dabigatran
factor Xa inhibitor- rivaroxaban/apixaban

48. Supportive care
• Nutritional support: enteral feeding NG Tube feeding if there’s
dysphagia
• Screen for dysphagia, to prevent aspiration
• Intermittent pneumatic compression for immobile patients
• Use of prophylactic-dose subcutaneous heparin has not been
established as beneficial

49. • • Use of hemodilution, IV albumin, to increase CBF has no any
benefit.
• Use of pharmacological and Non pharmacological neuroprotective
medications has no benefits.
• Regular skin assessment and skin hygiene.
• Use of prophylactic antibiotics and indwelling catheter should be
AVOIDED.

50. • Management of Cerebral edema:
• IV mannitol may be used to raise the serum osmolality.
• Hemicraniotomy reduces mortality by 50%
• Seizure control: antiepileptics for secondary prevention of
subsequent seizures.

51. Supportive care
• Rehabilitation : multidisciplinary approach
• Planning for discharge
• formal evaluation of the patients ADL
• ability to communicate and functional mobility
• Depression screening : use of antidepressants for diagnosed
depression

52. Prevention
• Primary prevention
• Healthy diet
• Smoking avoidance and cessation
• Blood pressure control: BP target <130/80mmHg
-SBP <120mmHg reduces risk of stroke & MI by 43% (SPRIN-Trial)
• Weight reduction, Increased physical activity
• Low dose statin
• Antiplatelet therapy: aspirin, clopidogrel

53. Secondary prevention (prevent further
strokes)
• Treatment of dyslipidemia:
- dietary, lifestyle modifications
- High intensity statin therapy : goal is to lower LDL-C by 50% or more in
patients <75yrs
- Screen for atrial fibrillation and initiate anticoagulant drug therapy to
reduce recurrent events
- Control of blood pressure in hypertensive patients
- Smoking cessation
- Screening and management of diabetes mellitus
- Surgery & stenting for carotid stenosis

54. Complications
ACUTE
• A-aspiration pneumonia
• P-post stroke seizures
• C-cerebral edema
• D-dehydration
• E-electrolyte derangement
• F-fever
• G-glycemia (hyper/hypo)
• H-hemorrhagic transformation
• I-increased ICP

55. • Long term complications
-DVT & PE
-Re-stroke
-UTI
-Constipation
-Bed sores
-Contractures

56. Stroke Mimics
• Hypoglycemia
• Hemiplegic migraine
• Todd’s paresis.
• Hypertensive encephalopathy
• Multiple sclerosis
• Wernicke’s encephalopathy.
• Viral encephalitis
• Head injury.
• Conversion disorder.
• Cerebral venous thrombosis.
• Compressive myelopathy

57. Conclusion
• Acute ischemic stroke is a medical emergency in which every minute
counts.
• Achievement of reperfusion can reverse neurologic deficits, even if
severe, and allow patients to regain function

58. References
• Wahab KW. The burden of stroke in Nigeria. Int J Stroke. 2008 Nov;3(4):290-2. doi:
10.1111/j.1747-4949.2008.00217.x. PMID: 18811746.
• Arshad Majid, MB, ChB, FRCP, Mounzer Kassab, MD , Pathophysiology of ischemic stroke
https://www.uptodate.com/contents/pathophysiologyof-ischemic-stroke#H21816470
• Natalia S Rost, Alexis Simpkins Overview of secondary prevention of ishemic stroke
• Edward C Jaunch Ischemic Stroke https://emedicine.medscape.com/article/1916852-
overview
• Wade S. Smith, S. Claiborne Johnston, J. Claude Hemphill, Ischemic stroke :
• Harrison Principle of Internal Medicine 20th Edition. 6. CONTINUUM (MINNEAP
MINN)2020;26(2, CEREBROVASCULAR DISEASE):435–456.
• https://www.stroke-manual.com/toast-stroke-classification/#1631720401843-ec8ba1b8-
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