Management of Acute Ischemic Stroke

6. A decrease in cerebral blood flow to zero causes death of brain tissue
within 4-10 minutes. Values < 16-18ml/100 g tissue per minute
Cause infarction within an hour and < 20 ml/100 g/min cause
Ischemia without infarction unless prolonged for several hrs.days.

7. If blood flow is restored to ischemic tissue before significant
infarction develops, the patient may experience only transient
symptoms, and the clinical syndrome is called TIA or
Transient Ischemic Attack.

10. Brain MRI with infarction in the right caudate and lenticular region

11. - 1] An orderly process of evaluation and
treatment is adopted.
- 2] The aim is to prevent further or reverse
brain injury.
- 3] Attend to and stabilize the patient’s
airway, breathing, and circulation.
- 4] Perform an emergency non contrast CT
scan to differentiate between ischemic and
hemorrhagic stroke.

12. Treatment of ischemic stroke falls into 6
categories
I] Medical Support:
- 1] Optimize cerebral perfusion in the
surrounding ischemic penumbra by promoting
collateral blood flow.
- 2] Blood pressure should be reduced only if it
exceeds 220/120 mm Hg, if there is malignant
hypertension, or concomitant myocardial
ischemia.
- 3] Blood pressure should be reduced if
>185/110 when thrombolytic therapy is
anticipated and kept < 180/105 post-
thrombolysis.

13. I] MEDICAL SUPPORT….CONTINUED
 - 4] Plasma glucose should be kept < 180 and > 70 mg/dl.
 - 5] Bed head end elevation, water restriction and IV
Mannitol to reduce cerebral oedema. Hemi-craniectomy
and sub-occciptal decompression may be needed.
 - 6] Attention is also directed toward preventing common
complications of bed-ridden patients - infections, DVT,
and PE.
 - 7] Fever should be treated with antipyretics and suface
cooling.
 -8] Hypovolemia should be avoided as it may lead to
hypotension and worsen the infarction.

14. II] INTRAVENOUS THROMBOLYSIS-
REVIEW ELIGIBILITY FOR t-PA

15. ADMINISTRATION OF Rtpa for AIS- Eligibility
INDICATION CONTRAINDICATIONS
1] Clinical diagnosis of stroke 1] Sustained BP >185/110
2[ Onset of symptoms to time of
drug
administration,<=4.5 hours
2] Bleeding diathesis
3] CT scan showing no
haemorrhage or
Edema >1/3 of the MCA territory
3] Recent head injury or ICH
4] Age > = 18 years 5] Major surgery in preceding 14
days
6] GIT bleeding in preceding 21
daysy
7] Recent myocardial infarction

16. II] INTRAVENOUS THROMBOLYSIS
• - Recombinant tissue plasminogen activator
[rTPA] is approved in the 3-4.5 hour window
period in the dose of 0.9 mg/kg body weight
[max 90 mg]. 10% is given as a bolus and the
remainder of the total dose over 1 hour as an
infusion.
• - No other antithrombotic treatment for 24
hours.
• - Avoid urethral catheterization for >= 2 hours of
rTPA administration.

17. III] ENDOVASCULAR
REVASCULARIZATION
• Endovascular mechanical thrombectomy is an
alternative or adjunctive treatment of acute
stroke in patients who are ineligible for, or have
contraindications to thrombolytics, or in those
who failed to achieve vascular recanalization with
IV thrombolytics.
• Occlusions in large intracranial vessels generally
involve a large clot volume and fail to open up
with IV rtPA alone and thus benefit from ER.

18. III] ENDOVASCULAR
REVASCULARIZATION…contd.
• The odds of a good outcome are dependent on
time and exceed 3 if done within 2 h and drop to
2 with 8 h elapse. Time window of 6 h is ideal.
• The outcome from ER are likely improved with IV
rtPA treatment prior to thrombectomy if the
patient is eligible for rtPA and it is safe to
administer. 30 mg IV bolus of Tenecteplase
shortens transport time to an endovascular unit.
• Exceeding the time window of 6 h appears to be
effective if the patient has good collaterals on CT
and MRI perfusion imaging techniques.

19.  - Aspirin in the dose of 150-300 mg od used
within 48 hours of acute ischemic stroke
proved to be effective in reducing both stroke
recurrence risk, and a reduction of disability,
dependence, and death at 6 months.
 - Combining Aspirin with Clopidogrel or
Ticagrelor following minor stroke orTIA is
effective at preventing a second stroke.

20. IV b] ANTICOAGULATION
• - The routine use of heparin and other
anticoagulants for atherothrombotic stroke is
not warranted.
- There may be benefit of anticoagulation for
halting progression of venous infarction due
to dural sinus thrombosis.

21. V] NEUROPROTECTION
• - Neuro-protection is the concept of providing a
treatment that prolongs the brain’s tolerance to
ischemia.
• - Hypothermia is a powerful neuro-protective
treatment in patients with cardiac arrest but is
not of benefit in patients with ischemic stroke
and is associated with increase in pneumonia
rates that could adversely affect stroke
outcomes.

22. VI] STROKE CENTERS AND REHABILITATION
• - Use of standardized stroke orders.
• Dedicated stroke teams that provide emergency
24 hour evaluation of acute stroke patients for
acute medical management.
• - Consideration of thrombolysis or endovascular
treatments are essential components of primary
and comprehensive stroke centres respectively.
• - Proper rehabilitation of the stroke patients
includes early physical, occupational, and
speech therapy and constrained movement
therapy

23. Definition of TIA
- TIAs are strokes “ Ministrokes” that last only
briefly, < 24 hours, but most last < 1 hour.
- A normal brain imaging study following a TIA is
diagnostic.
- TIA’s arise from emboli to the brain or from in
situ thrombosis of an intracranial vessel.
- With a TIA the occluded vessel reopens and
neurologic function is restored.

25. TIAs may herald a stroke. They are an important risk factor that
should be considered separately and urgently.

26. TREATMENT OF TIA
• - The combination of aspirin and clopidogrel was
found to prevent stroke following TIA better than
aspirin alone.
• Recently ticagrelor 180 mg loading dose and then 90
mg twice daily was tested in combination with aspirin.
• Aspirin and ticagrelor also showed benefit in
preventing a stroke, and is more to be favored, because
of the absence of genetic heterogenity in platelet
inhibition related to CYP2C19 polymorphism that leads
to poor metabolism of clopidogrel into its active form.

27. Primary and Secondary Prevention of
Stroke and TIA
1] GENERAL PRINCIPLES:
- Many medical and surgical interventions,
as well as lifestyle modifications are
available for preventing stroke.
- Identification and control of modifiable
risk factors, and especially hypertension
is the best strategy to reduce the burden
of stroke and TIAs.

28. 2] ATHEROSCLEROSIS RISK FACTORS
• Hypertension is the most significant of the
risk factors and all hypertension should be
treated to a target of <130/80.
• Statin drugs reduce the risk of stroke even in
patients without elevated LDL or low HDL. A
LDL level of < 70 mg/dl lowers recurrent stroke
risk better than an LDL of 100-110 mg/dl.

29. 2] ATHEROSCLEROSIS RISK
FACTORS…contd
• Pioglitazone a peroxisome proliferator-activated
receptor gamma is effective in lowering vascular
events in patients with stroke and prediabetes or
insulin resistance alone. Diabetes prevention is
likely the most effective strategy for primary and
secondary stroke prevention.
• Platelet anti-aggregation agents can prevent
atherothrombotic events including TIA and stroke,
by inhibiting the formation of intraarterial platelet
aggregates.

30. 3] ANTIPLATELET AGENTS FOR STROKE
PREVENTION
• Platelet anti-aggregation agents can prevent
atherothrombotic events, including TIA and
stroke by inhibiting the formation of intra-
arterial platelet aggregates.
• Aspirin and clopidogrel, the combination of
aspirin plus extended-release dipyridamole, and
recently ticagrelor are the anti-platelet agents
most commonly used for this purpose.

31. 3] ANTIPLATELET AGENTS FOR STROKEPREVENTION…contd

33. PHOSPHODIESTERASE INHIBITOR ACTION OF DIPYRIDAMOLE

34. 3] ANTIPLATELET AGENTS FOR STROKE
PREVENTION…contd.
- Anti-platelet agents reduce the risk of all
important vascular athero-thrombotic [events
like ischemic stroke, MI, and death due to all
vascular causes] in patients at risk from these
events.
- The overall relative reduction in risk of nonfatal
stroke is ~ 25-30% and of all vascular events it is
~ 25%.
- The absolute reduction varies considerably,
depending on the patient’s existing risk.

35. When considering antithrombotic therapy for secondary
stroke prevention for non-cardio-embolic strokes and
TIAs:
- 1] Aspirin initial load of 300 mg followed by 75 mg
- And add:
- 2a] Clopidogrel 300 mg load followed by 75 mg daily
- or
- 2b] Ticagrelor 180 mg load followed by 90 mg twice daily
The duration of the regimen for stroke is dual anti-platelet
[DAP] regimen for 3 months followed by aspirin alone.
The duration of the above regimen for TIAs is DAP regimen
for 21-30 days followed by aspirin alone.

36. 4] ANTICOAGULATION THERAPY AND
EMBOLIC STROKE PREVENTION
1] ATRIAL FIBRILLATION:
• Xa inhibitor Apixaban 5 mg bid for non-valvular atrial
fibrillation with CHA2dS2-VASc score of > or = 2.
• Aspirin 75 mg plus Clopidogrel 75 mg in patients who
cannot take oral anticoagulants.
• VKAs for valvular atrial fibrillation or mechanical heart
valve.
• Intermittent AF has the same risk as chronic AF.
2] MYOCARDIAL INFARCTION:
3 month course of oral anticoagulants when there is an
anterior Q wave infarction, significant LV dysfunction,
congestive heart failure, mural thrombosis, or AF. OACs are
recommended long term if AF persists,

37. 4] ANTICOAGULATION THERAPY AND
EMBOLIC STROKE PREVENTION
3] PROSTHETIC HEART VALVE:
The intensity of anticoagulation and or antiplatelet
therapy is dictated by the type of prosthetic valve
and its location. The oral antithrombin inhibitor
Dabigatran in the dosage or 150 mg/d may be
less effective than Warfarin.
4] If the embolic source cannot be eliminated
anticoagulation should be continued indefinitely.
5] Antidote for Xa inhibitors is andexanet alfa.
Antidote for antithrombin inhibitor Dabigatran is
Idarucizumab.

38. 5] ANTICOAGULATION THERAPY AND
NON CARDIOGENIC STROKE
• Data does not support the use of long term VKA for
preventing athero-thrombotic stroke for either intra-
cranial or extra-cranial cerebrovascular disease.
• Use of factor Xa medications for prevention of embolic
stroke of unknown source failed to show benefits
compared to treatment with anti-platelet medication.
• So the current practice is to prescribe aspirin for
secondary stroke prevention in noncardiogenic cerebral
emboli except in:
1] Stroke associated with cancer- Apixaban 5 mg bid
2] Stroke associated with APLS – Warfarin with target
INR2-3

39. CAROTID
ATHEROSCLEROSIS
 Carotid atherosclerosis can be removed
surgically by endarterectomy or mitigated
with
endovascular stenting with or without
baloon angioplasty.
Anticoagulation has not been directly
compared with anti-platelet therapy for
carotid disease.

40. CAROTID ATHEROSCLEROSIS

41. 1] SURGICAL THERAPY
 Symptomatic Carotid Stenosis - Patients with recent
symptomatic hemispheric ischemia, high-grade
stenosis [>70%] in the appropriate internal carotid
artery, and an institutional peri-operative morbidity
and mortality rate of > = 6% should undergo carotid
endarterectomy.
 Endarterectomy is most beneficial when performed
within 2 weeks of symptom onset. Benefit is most
pronounced in patients > 75 years, and men benefit
more than women.

42. 1] SURGICAL THERAPY…Contd.
 Asymptomatic Carotid Stenosis – The natural history
of asymptomatic stenosis is an ~ 2% per year stroke
rate, whereas symptomatic patients experience a 13%
per year risk of stroke.
 Whether to recommend carotid revascularization
surgery for an asymptomatic patient is somewhat
controversial and depends on many factors, including
patient preference, age, gender, and comorbidities.

43. SURGICAL THERAPY – Contd.
 Medical therapy for reduction of atherosclerosis risk
factors, including cholesterol lowering agents and
anti-platelet medications is generally recommended
for patients with asymptomatic carotid stenosis.
 It is imperative to counsel the patient about TIA’s so
that therapy can be revised if symptoms develop.

44. Carotid Endarterectomy Surgery

45. 2] ENDOVASCULAR THERAPY
 Balloon angioplasty coupled with stenting is being
used with increasing frequency to open stenotic
carotid arteries and maintain their patency.
 These techniques can treat carotid stenosis not only at
the bifurcation but also near the skull base and in the
intracranial segments.
 In meta-analysis carotid endarterectomy is less morbid
in older patients aged > 70 than is stenting.
 Investigation is ongoing in asymptomatic patients to
compare medical therapy to stenting and CEA.

47. 3] BYPASS [EC-IC] SURGERY
• Extracranial to intracranial bypass surgery has
been proven ineffective for atherosclerotic
stenoses that are inaccessible to conventional
CEA.
• In patients with recent stroke, and associated
carotid occlusion, and evidence of inadequate
perfusion of the brain as measured with PET, no
benefit from EC-IC bypass was found in a trial
stopped for futility.

48.  - If the neurological opinion is that no other
source of stroke is identified and consultation
with a cardiologist knowledgeable about
PFO closure supports intervention,
endovascular PFO closure is recommended.

50. 5] INTRACRANIAL ATHEROSCLEROSIS
• - Routine use of intracranial stenting of
intracranial atherosclerosis was found to be
dramatically harmful compared to aspirin in
the SAMMPRIS [Stenting and Aggressive
Medical Management for Preventing
Recurrent Stroke in Intracranial Stenosis] trial.
• - Medical therapy with aspirin is superior in
patients with symptomatic stenosis of a major
intracranial vessel.

51.  - Limited evidence exists to support short-
term use of anti-coagulants, regardless of
the presence of intracranial haemorrhage.

52. ACLS for Acute Stroke