Dr. Syed Muhammad Ali Shah provides an overview of ischemic stroke. Key points include: - Stroke is defined as rapid onset of neurological deficit lasting over 24 hours caused by a vascular issue. - Risk factors include atrial fibrillation, hypertension, smoking, obesity, and high cholesterol. - Diagnosis involves investigations like CT scans and MRI. Treatment depends on the cause but may include thrombolysis within 4.5 hours, aspirin, rehabilitation, and preventing future strokes through controlling risk factors. - Future advances include endovascular therapies to remove clots and research on neuroprotection strategies. Prevention through lifestyle changes and medications can reduce stroke risk.

1. ISCHEMIC STROKE
Dr. Syed Muhammad Ali Shah
RMO/PGR
Dept. of Medicine ABSTH/NSMC

2. HISTORY OF STROKE
• Hippocrates first recognized stroke over 2,400 years ago.
• At this time stroke was called apoplexy, which means
"struck down by violence" in Greek.
• In mid-1600s that Jacob Wepfer - bleeding in the brain or
blockage in one of the brain's blood vessels
• In 1928, apoplexy was divided into categories based on the
cause of the blood vessel problem.
• This led to the terms stroke or "cerebral vascular accident
(CVA)."
http://www.hopkinsmedicine.org/healthlibrary/conditions/nervous_system_disorders/history_of_stroke_85,P00223/

3. DEFINITION
• Stroke is defined as a syndrome of rapid onset
of cerebral deficit (usually focal) lasting >24 h
or leading to death, with no cause apparent
other than a vascular one.
Kumar & Clark’s Clinical Medicine 8th Ed.

4. Epidemiology of Stroke
• Stroke remains the third leading cause of
death worldwide.
• No large scale epidemiological studies are
available to determine the true incidence of
stroke in Pakistan.
• Estimated annual incidence is 250/100,000,
translating to 350,000 new cases every year.
http://www.jpma.org.pk/full_article_text.php?article_id=1444

5. RISK FACTORS
*Davidson’s Principles and Practice of Medicine 22nd Ed.

6. Classification of Stroke

7. CAUSES OF STROKE
Cardiac source
•Arrhythmias
•Valve disease
•Dilated cardiomyopathy
•Recent myocardial infarction
•Paradoxical emboli
•Aorta
Large-vessel disorders
•Atherosclerosis or dissection in the carotid or
vertebrobasilar system
Small-vessel occlusive disease
•Hypertension-induced disease
•Isolated central nervous system angiitis
•Systemic lupus erythematosus
Hematologic disorders
•Polycythemia
•Thrombocytosis
•Severe leukocytosis (acute leukemia)
•Antithrombin III defi ciency
•Protein C defi ciency,
•Protein S deficiency
•Factor V Leiden mutation
•Hypercoagulable state

8. Pathology
• Ischemia of brain occurs due to thromboembolic
event
• Reduction of blood flow reduces supply of oxygen
and hence ATP.
• H+ is produced by anaerobic metabolism of
available glucose.
• Energy-dependent membrane ionic pumps fail,
leading to cytotoxic oedema and membrane
depolarisation, allowing calcium entry and
releasing glutamate.
*Davidson’s Principles and Practice of Medicine 22nd Ed

9. Pathology
• Calcium enters cells via glutamate-gated channels
and activates destructive intracellular enzymes,
destroying intracellular organelles and cell
membrane, with release of free radicals.
• Free fatty acid release activates pro-coagulant
pathways that exacerbate local ischemia.
• Glial cells take up H+, can no longer take up
extracellular glutamate and also suffer cell death,
leading to liquefactive necrosis of whole arterial
territory.
Davidson’s Principles and Practice of Medicine 22nd Ed

10. Arterial Cerebral Circulation
• The arterial cerebral circulation is normally
divided into
– Anterior cerebral circulation
– Posterior cerebral circulation
http://emedicine.medscape.com/article/1916852-clinical

12. Symptoms & Signs
• Hemiparesis
• Monoparesis
• Hemisensory deficits
• Monocular or binocular
visual loss
• Visual field deficits
• Diplopia
• Dysarthria
• Facial drop
• Ataxia
• Vertigo (rarely in
isolation)
• Aphasia
• Sudden decrease in the
level of consciousness
http://emedicine.medscape.com/article/1916852-clinical

13. Stroke, April 2003, Adams et al, Management of Patients With Ischemic Stroke

14. Stroke, April 2003, Adams et al, Management of Patients With Ischemic Stroke

15. Rapid Assessment of Suspected
Stroke
ROSIER scale
– Unilateral facial weakness +1
– Unilateral grip weakness +1
– Unilateral arm weakness +1
– Unilateral leg weakness +1
– Speech loss +1
– Visual field defect +1
– Loss of consciousness −1
– Seizure −1
Total (−2 to +6); score of > 0 indicates stroke is possible cause
Exclude hypoglycaemia
• Bedside blood glucose testing
Davidson’s Principles and Practice of Medicine 22nd Ed

16. Investigations

17. Management
General Management1
• Airway
– Perform bedside swallow screen and keep patient nil by mouth if
swallowing unsafe or aspiration occurs
• Breathing
– Check respiratory rate and oxygen saturation and give oxygen if
saturation < 95%
• Circulation
– Check peripheral perfusion, pulse and blood pressure and treat
abnormalities with fluid replacement, anti-arrhythmics and inotropic
drugs as appropriate
• Hydration
– If signs of dehydration, give fluids parenterally or by nasogastric tube
www.pakneurology.net
Davidson’s Principles and Practice of Medicine 22nd Ed
http://jama.jamanetwork.com/article.aspx?articleid=195305

18. • Nutrition
– Assess nutritional status and provide nutritional supplements if necessary
– If dysphagia persists for > 48 hrs, start feeding via a nasogastric tube
• Medication
– If patient is dysphagic, consider alternative routes for essential medications
• Blood pressure
– Unless there is heart or renal failure, evidence of hypertensive
encephalopathy or aortic dissection, do not lower blood pressure in first week
as it may reduce cerebral perfusion.
– Target blood pressure in patients who are not candidates for rt-PA should have
a systolic blood pressure of less than 220 mm Hg and a diastolic blood
pressure of less than 120 mm Hg.
– A blood pressure less than these values does NOT warrant anti-hypertensive
medicines.
– Blood pressure often returns towards patient’s normal level within first few
days
http://jama.jamanetwork.com/article.aspx?articleid=195305

19. • Blood glucose
– Hyperglycemia has detrimental outcomes after stroke.
It increases the chances of hemorrhagic conversion.
– Persistent hyperglycemia at the rate of > 200 mg / dl
independently predicts stroke expansion
– Monitor closely to avoid hypoglycaemia
• Temperature
– Increased body temperature in the setting of acute
stroke is associated with poor neurologic outcomes
as raised brain temperature may increase infarct
volume
– If pyrexic, investigate and treat underlying cause &
control with antipyretics
– Common reasons are aspiration pneumonia, IV line
phlebitis and urinary tract infection.

20. • Pressure areas
– Reduce risk of skin breakdown
– Treat infection
– Maintain nutrition
– Provide pressure-relieving mattress
– Turn immobile patients regularly
• Incontinence
– Check for constipation and urinary retention; treat
appropriately
– Avoid urinary catheterisation unless patient is in acute
urinary retention or incontinence is threatening
pressure areas
• Mobilisation
– Avoid bed rest

21. Thrombolysis
• IV thrombolytic therapy with recombinant tissue
plasminogen activator (rtPA; 0.9 mg/kg to a
maximum of 90 mg, with 10% given as a bolus
over 1 minute and the remainder over 1 hour) is
effective in reducing the neurologic deficit in
selected patients
• Patients should receive tPA within 1 hour after
arriving to the hospital but not more than 4.5
hours after the onset of ischemic symptoms.
CMDT 2015
www.pakneurology.net
http://jama.jamanetwork.com/article.aspx?articleid=195305

22. • In patients not eligible for thrombolytic
therapy, the immediate administration of
aspirin 325 mg orally daily is indicated.
• Anticoagulant drugs ONLY be started in the
setting of atrial fibrillation with warfarin
(target INR 2.0–3.0) or dabigatran (150 mg
twice daily)
Davidson’s Principles and Practice of Medicine 22nd Ed
CMDT 2015
http://jama.jamanetwork.com/article.aspx?articleid=195305

23. • Elevated intracranial pressure is managed by
head elevation and osmotic agents such as
mannitol.
• Decompressive hemicraniectomy for
malignant middle cerebral artery infarctions
may reduce mortality and improve functional
outcome in some instances.
Davidson’s Principles and Practice of Medicine 22nd Ed
CMDT 2015
http://jama.jamanetwork.com/article.aspx?articleid=195305

24. Physical Therapy
• Passive movements at an early stage will help prevent
contractures.
• As cooperation increases and some recovery begins,
active movements will improve strength and
coordination.
• In all cases, early mobilization and active rehabilitation
are important.
• Occupational therapy may improve morale and motor
skills
• Speech therapy may help expressive dysphasia or
dysarthria.
CMDT 2015
www.pakneurology.net

25. Steroids
• Treatment with corticosteroids did not appear to
show any improvement in functional outcomes of
stroke survivors.
• Usage of steroids in these cases may elicit unwanted
adverse effects such as hyperglycemia and infections.
Neuroprotection and Neurotonics
• No single trial has shown convincing benefit of stroke
neuroprotection and efficacy of intervention is
doubtful.
Qizilbash N, Lewington SL, Lopez-Arrieta JM. Corticosteroids for acute ischaemic stroke. Cochrane Database Syst Rev. 2002:CD000064
Lutsep HL, Clark WM. Neuroprotection in acute ischemic stroke. Current status and future potential. Drugs R D. 1999; 1:3-8
Wahlgren NG, Ahmed N. Neuroprotection in cerebral ischemia: Facts and fancies—the need for new approaches. Cerebrovasc Dis. 2004; 17 Suppl 1:153-
166

26. Secondary Prevention
• Antithrombotic therapy
– Aspirin in a dose ranging from 75 to 300 mg is efficacious
in stroke prevention.
– Clopidogrel is marginally better at increased cost and is
therefore suggested in those with concomitant peripheral
vascular disease and / or intolerance to aspirin.
• Dose adjusted warfarin is suggested in an INR 2-3 for
those who have intermittent or continous atrial
fibrillation.
Davidson’s Principles and Practice of Medicine 22nd Ed
CMDT 2015
www.pakneurology.net
http://jama.jamanetwork.com/article.aspx?articleid=195305

27. • Lipid Control1
– Atorvastatin 80 mg/day significantly reduced the risk of
stroke in patients who previously had a stroke or (TIA) and
who had no known cardiovascular disease.
– Target goal for cholesterol lowering LDL-C of <100 mg/dL
and LDL-C of <70 mg/dL for very-high-risk persons with
multiple risk factors
• Blood Pressure Control2’3
– Mean blood pressure fall of 5 mm Hg leads to a one third
reduction of stroke
– If BP > 130/70 mmHg 1–2 weeks after onset use thiazide
diuretic and/or ACE inhibitor
1. Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) study
2. PROGRESS trial
3. Davidson’s Principles and Practice of Medicine 22nd Ed
www.pakneurology.net
http://jama.jamanetwork.com/article.aspx?articleid=195305

28. • Smoking
• Obesity
• Exercise- regular physical activity
• Dietry salt restriction
www.pakneurology.net
http://jama.jamanetwork.com/article.aspx?articleid=195305

30. Surgical Interventions
Carotid Endarterectomy
When arteriography reveals a surgically
accessible highgrade stenosis (70–99% in
luminal diameter) on the side appropriate to
carotid ischemic attacks - operative treatment
(carotid endarterectomy) or endovascular
intervention reduces the risk of ipsilateral
carotid stroke
CMDT 2015
http://jama.jamanetwork.com/article.aspx?articleid=195305

31. Stroke in Future
Folate Supplements for Stroke Prevention1
Among adults with hypertension in China without
a history of stroke or MI, the combined use of
enalapril and folic acid, compared with enalapril
alone, significantly reduced the risk of first stroke.
These findings are consistent with benefits from
folate use among adults with hypertension and
low baseline folate levels.
1.http://jama.jamanetwork.com/article.aspx?articleid=2205876

32. Stroke in Future
Endovascular Therapy for Ischemic Stroke with
Perfusion-Imaging Selection
In patients with ischemic stroke with a proximal
cerebral arterial occlusion and salvageable tissue
on CT perfusion imaging, early thrombectomy
with the Solitaire FR stent retriever, as compared
with alteplase alone, improved reperfusion, early
neurologic recovery, and functional outcome.
http://www.nejm.org/doi/full/10.1056/NEJMoa1414792#t=abstract