8/8/2019 Update on Management of Ischemic Stroke 2
1/41
Update on
Management of Ischemic Stroke
Dr Muhammad Wazir Ali Khan
Assistant Professor of NeurologySheikh Zayed Medical College,Rahim Yar Khan
8/8/2019 Update on Management of Ischemic Stroke 2
2/41
Historical Background
During the 17th and 18th centuries, it wasrecognized that the dead brains containedhaemorrhages and softenings and that braindamage could result from either bleeding orocclusion of the vital blood supply.
During the 19th and early 20th centuries,correlating the neurological symptoms and signs
found in stroke patients during life with theanatomical region of damage in the brain foundafter death.
8/8/2019 Update on Management of Ischemic Stroke 2
3/41
Historical Background
During the 20th century, clinicopathologicalanalysis of stroke syndromes was done.
Clinical symptoms were attributed to definitecerebral anatomical areas.
Correlation between cardiac and cranial vasculardisease and stroke and TIA were identified.
8/8/2019 Update on Management of Ischemic Stroke 2
4/41
Historical Background
Explosive advances occurred in brainimaging
Computed tomography, CT Magnetic resonance imaging, MRI
Single-photon emission computed tomography, SPECT
Positron emission tomography, PET
Digital subtraction angiography, DSA
MR angiography, MRA CT angiography, CTA
Extracranial and transcranial ultrasonography.
8/8/2019 Update on Management of Ischemic Stroke 2
5/41
Pathophysiology
The brain is the most metabolically active organ inthe body.
It represents only 2% of the body's mass.
It requires 15-20% of the total resting cardiacoutput to provide the necessary glucose andoxygen for its metabolism.
8/8/2019 Update on Management of Ischemic Stroke 2
6/41
Pathophysiology
Ischemic strokes result from events that limit orstop blood flow, such as Embolism
Thrombosis in situ
Relative hypoperfusion.
As blood flow decreases, neurons ceasefunctioning.
Irreversible neuronal ischemia and injury begin atblood flow rates of less than 18 mL/100 mg/min.
8/8/2019 Update on Management of Ischemic Stroke 2
7/41
Ischemic cascade
Within seconds to minutes of the loss of glucoseand oxygen delivery to neurons, the cellularischemic cascade begins. There is cessation of the normal electrophysiologic function of the
cells.
The resultant neuronal and glial injury producesedema in the ensuing hours to days after stroke,
causing further injury to the surrounding tissues.
8/8/2019 Update on Management of Ischemic Stroke 2
8/41
Ischemic cascade
Brain regions without significant flow are referredto collectively as the core. Neuronal cells in these areas are presumed to die within minutes of
stroke onset.
Zones of decreased or marginal perfusion arecollectively called the ischemic penumbra. Tissue in the penumbra can remain viable for several hours
because of marginal tissue perfusion. Pharmacologic interventions target this penumbra.
8/8/2019 Update on Management of Ischemic Stroke 2
9/41
Mechanisms of Stroke
Embolic strokes Emboli of cardiac or arterial origin.
Cardiac sources include:
Atrial fibrillationRecent myocardial
infarction
Prosthetic valves
Native valvular disease
Endocarditis
Mural thrombiDilated cardiomyopathy
Patent foramen ovale.
Arterial sources
include: Atherothrombolic
Cholesterol emboli thatdevelop in the arch of theaorta and in the
extracranial arteries.
8/8/2019 Update on Management of Ischemic Stroke 2
10/41
Mechanisms of Stroke
Thrombotic strokes Thrombotic strokes include large-vessel strokes and
small-vessel or lacunar strokes.
In situ occlusions on atherosclerotic lesions in thecarotid, vertebrobasilar, and cerebral arteries, typicallyproximal to major branches.
Thrombogenic factors may include:
Injury to and loss of endothelial cells exposing thesubendothelium
Platelet activation by the subendothelium
Activation of the clotting cascade, inhibition of fibrinolysis, andblood stasis.
8/8/2019 Update on Management of Ischemic Stroke 2
11/41
Mechanisms of Stroke
Lacunar Strokes 20% of all ischemic strokes.
They occur when the penetrating branches becomeoccluded.
Causes include microatheroma, lipohyalinosis, fibrinoidnecrosis secondary to hypertension or vasculitis, hyalinearteriosclerosis, and amyloid angiopathy.
Watershed Infarcts Develop from relative hypoperfusion in the most distal
arterial territories.
8/8/2019 Update on Management of Ischemic Stroke 2
12/41
Epidemiology of Stroke
United States 795,000 strokes occur each year.
625,000 are ischemic strokes.
By the year2025, the annual number of strokes is
expected to reach 1 million. Currently, more than 4.4 million people in the United
States are stroke survivors.
International Population older than 65 years will rise from 390 million
now to 800 million by 2025. The WHO estimates that 15 million people suffer a
stroke worldwide each year, resulting in 5 million deathsand 5 million people permanently disabled.
8/8/2019 Update on Management of Ischemic Stroke 2
13/41
Epidemiology of Stroke
Race Stroke has a higher incidence in the black population
than in the white population.
Blacks have an age-adjusted risk of death from strokethat is 1.49 times that of whites.
Hispanics have a lower overall incidence of stroke thanwhites and blacks but more frequent lacunar strokes and
stroke at an earlier age.
8/8/2019 Update on Management of Ischemic Stroke 2
14/41
Epidemiology of Stroke
Sex In patients younger than 60 years, the incidence of
stroke is greater in males (3:2 ratio).
Males have a stroke incidence slightly lower than
females and lower death rates than females.
Age Stroke can occur in patients of all ages, including
children.
Risk of stroke increases with age, especially in patientsolder than 64 years, in whom 75% of all strokes occur.
8/8/2019 Update on Management of Ischemic Stroke 2
15/41
Risk factors for ischemic stroke
Non-modifiable risk factors include: Age
Race
Sex
Ethnicity History of migraine headaches
Sickle cell disease
Fibromuscular dysplasia
H
eredity
8/8/2019 Update on Management of Ischemic Stroke 2
16/41
Risk factors for ischemic stroke
Modifiable risk factors include the following: Hypertension (the most important)
Diabetes mellitus
Cardiac disease - Atrial fibrillation, valvular disease,
mitral stenosis, Hypercholesterolemia
Transient ischemic attacks (TIAs)
Carotid stenosis
Hyperhomocystinemia
Lifestyle issues - Excessive alcohol intake, tobacco use,illicit drug use, obesity, physical inactivity
Oral contraceptive use.
8/8/2019 Update on Management of Ischemic Stroke 2
17/41
Stroke-Differential Diagnosis
Venous Infarction
Multiple Sclerosis - a Demyelinating Plaque
Mass Lesions:
Brain tumour Abscess
Subdural haematoma
Carotid or Vertebral Artery Dissection
Polycythaemia, Hyperviscosity Syndromes
Fat and Air Embolism
Rarities: Arteritis, Neurosyphilis, SLE,Mitochondrial Disease.
8/8/2019 Update on Management of Ischemic Stroke 2
18/41
Management of Ischemic Stroke
Pre-hospital/EMS management
Hospital care
Secondary prevention
Rehabilitation
Physical therapy Speech therapy
Occupational therapy
8/8/2019 Update on Management of Ischemic Stroke 2
19/41
NINDS and ACLS Recommended Stroke Evaluation Time
Benchmarks for Potential Thrombolysis Candidate
Time Interval Time Target
Door to doctor 10 min
Access to neurologic expertise 15 min
Door to CT scan completion 25 min
Door to CT scan interpretation 45 min
Door to treatment 60 min
Admission to monitored bed 3 h
8/8/2019 Update on Management of Ischemic Stroke 2
20/41
General Management of Patients With Acute
Stroke
BloodGlucose
Treat hypoglycemia with D50Treat hyperglycemia with insulin if serum glucose >200 mg/dL
Seizures Occur in 2%focal or generalized. Use conventional AED.
Cardiacmonitoring
Continuous monitoring for ischemic changes or atrial fibrillation
Elevated ICP 1 g/kg stat, then 50 g every 2 or 3 h. Hyperventilate
Intravenousfluids
Avoid D5W and excessive fluid administrationIV isotonic sodium chloride solution at 50 mL/h unlessotherwise indicated
Oral Intake NPO initially; aspiration risk is great, Use NG/PEG tube feed
Oxygen Supplement if indicated (Sa02
8/8/2019 Update on Management of Ischemic Stroke 2
21/41
Blood Pressure Management in Patients With
Stroke*
Patients who are candidates for rtPA
Pre-treatment
SBP >185 or
DBP >110 mmH
g
Labetalol 10-20 mg IVP 1-2 doses orEnalapril 1.25 mg IVP
Post-treatment
DBP >140 mm Hg Sodium nitroprusside (0.5 mcg/kg/min)
SBP >230 mm Hg orDBP 121-140 mm Hg
Labetalol 10-20 mg IVP and consider labetalolinfusion at 1-2 mg/min or nicardipine 5 mg/h IVinfusion and titrate
SBP 180-230 mm Hg orDBP 105-120 mm Hg
Labetalol 10 mg IVP, may repeat and double every10 min up to maximum dose of 150 mg
*Adopted from 2005 Advanced Cardiac Life Support (ACLS) guidelines and 2007 American Stroke Association ScientificStatement
8/8/2019 Update on Management of Ischemic Stroke 2
22/41
Blood Pressure Management in Patients With
Stroke*
Patients Who are not Candidates for rtPA
DBP >140 mm HgSodium nitroprusside 0.5 mcg/kg/min; may reduceapproximately 10-20%
SBP >220 orDBP 121-140 mm Hg orMAP >130 mm Hg
Labetalol 10-20 mg IVP over 1-2 min; may repeatand double every 10 min up to maximum dose of150 mg or nicardipine 5 mg/h IV infusion and titrate
SBP
8/8/2019 Update on Management of Ischemic Stroke 2
23/41
Acute Therapy of Ischemic Stroke
Hemodynamic Considerations Cerebral perfusion depends on the mean systemic
arterial pressure (MAP).
Areas of brain distal to narrowed or occluded arteriesmay be supplied by collateral vessels.
When fully dilated flow in these vessels becomespassively dependent on the MAP.
Therefore, it is desirable to maintain MAP high in thesetting of acute stroke.
8/8/2019 Update on Management of Ischemic Stroke 2
24/41
Acute Therapy of Ischemic Stroke
Hemodynamic Considerations It is common for patients with acute stroke to have acute
BP elevations on presentation.
In general, this BP should not be lowered, unless BPlowering is necessary to fulfill criteria for safethrombolysis, or unless acute medical issues demand it:
Acute myocardial infarction
Aortic dissection
H
ypertensive crisis with end-organ involvement. Congestive heart failure (CHF)
Renal failure
Hypertensive encephalopathy
8/8/2019 Update on Management of Ischemic Stroke 2
25/41
Acute Therapy of Ischemic Stroke
Hemodynamic Considerations Consensus guidelines from the ASA suggest therapy if:
Diastolic BP above 120
Systolic BP above 220
Target BP for tissue plasminogen activator (TPA)therapy:
Systolic BP less than or equal to 185
Diastolic BP less than or equal to 110
8/8/2019 Update on Management of Ischemic Stroke 2
26/41
Surgical Care
Surgical evacuation in case of hemorrhage or hemorrhagictransformation following t-PA.
The management of life-threatening elevations of ICP.
Hemicraniectomy to treat life-threatening ICP: Shorter ICU stays
Lower mortality rate if surgery is performed before clinicaldeterioration.
These benefits are not confirmed by clinical trials.
8/8/2019 Update on Management of Ischemic Stroke 2
27/41
Investigations
The purpose of investigations in both stroke andTIA is to: Confirm clinical diagnosis.
Distinguish between haemorrhage and thrombo-embolicinfarction.
Look for underlying causes of disease and to directtherapy, either medical or surgical.
8/8/2019 Update on Management of Ischemic Stroke 2
28/41
CT Scan
CT is most important in the evaluation of patientswith acute stroke.
Noncontrast CT is very sensitive in detectingintracerebral and subarachnoid hemorrhage, aswell as subdural hematomas.
Infarctions are usually detectable at 1 week
although 50% are never detected on CT.
8/8/2019 Update on Management of Ischemic Stroke 2
29/41
CT Scan
CT may demonstrate other pathologies: Neoplasm Aneurysm/Arteriovenous malformation Abscess
H
ydrocephalus
CT angiography may demonstrate the location ofvascular occlusion.
CT perfusion studies together with CT angiographyare becoming more available and utilized in theacute evaluation of stroke patients.
8/8/2019 Update on Management of Ischemic Stroke 2
30/41
Brain Infarction-CT
Early Day 3
8/8/2019 Update on Management of Ischemic Stroke 2
31/41
Brain Infarction-CT
8/8/2019 Update on Management of Ischemic Stroke 2
32/41
MRI and MRA
MRI with magnetic resonance angiography (MRA)is a major advance in the neuroimaging of stroke.
MRI provides great detail in structural andmetabolic imaging.
Diffusion-weighted MRI (DW-MRI) can detectareas of ischemic brain injury earlier than standard
T1/T2-weighted MRI images or CT scan.
8/8/2019 Update on Management of Ischemic Stroke 2
33/41
MRI and MRA
Perfusion MRI (PW-MRI) uses injected contrastmaterial to demonstrate areas of decreasedperfusion.
These sequences combined with DW-MRI yieldareas of DW-MRI/PW-MRI mismatch, therebyidentifying potentially salvageable tissues.
MRA is a noninvasive technique whichdemonstrates vascular anatomy and occlusivedisease of the head and neck.
8/8/2019 Update on Management of Ischemic Stroke 2
34/41
MRI
8/8/2019 Update on Management of Ischemic Stroke 2
35/41
MCA Infarction DWI & MRA
8/8/2019 Update on Management of Ischemic Stroke 2
36/41
DWI & PWI-MRI
8/8/2019 Update on Management of Ischemic Stroke 2
37/41
Other studies
Digital subtraction angiography, DSA Gold standard for demonstrating vascular lesions:
Occlusions, stenoses, dissections, and aneurysms.
It also allows for intra-arterial therapies.
Intra-arterial thrombolytics. Investigational catheter devices.
Angiography requires special facilities and a skilledoperator and it carries a stroke risk of 1%.
MR spectroscopy is an experimental techniquedistinguishing areas of salvageable neurons.
8/8/2019 Update on Management of Ischemic Stroke 2
38/41
Other studies
Carotid duplex scanning Performed for carotid stenosis and to stratify patients
either for medical management or carotid intervention.
Transcranial Doppler ultrasonography (TCD) To assess the location and degree of arterial occlusions
in extracranial carotid and large intracranial vessels
It can also be used to detect restoration of flow afterthrombolytic therapy.
Single-photon emission computed tomography(SPECT) defines areas of altered regional bloodflow.
8/8/2019 Update on Management of Ischemic Stroke 2
39/41
Other studies
Echocardiography: For evaluation of possible cardiogenic sources of stroke. TEE can evaluate the aortic arch and thoracic aorta for
plaques or dissections.
Electrocardiography/ECG: ECG may demonstrate cardiac arrhythmias, such as
atrial fibrillation, or may indicate acute ischemia. All patients with stroke should have an ECG as part of
their initial evaluation.
Chest radiography should be performed whenclinically indicated.
8/8/2019 Update on Management of Ischemic Stroke 2
40/41
Other studies
Lumbar puncture: This is indicated only in unusual circumstances, such as
when blood syphilitic serology is positive.
Blood for: Polycythaemia Infection Vasculitis Thrombophilia
Syphilitic serology Clotting studies Autoantibodies Lipids
8/8/2019 Update on Management of Ischemic Stroke 2
41/41
Thrombolysis in acute ischemic stroke
0.9 mg/kg IV TPA IV under 3 hrs of onset Inclusion Criteria:
onset 15 SBP >186 or DBP >110, Hg