stroke update serum markers for acute neurologic conditions, jordan barnett md
DESCRIPTION
2007 Lecture for residents regarding serum markers for CVA/Stroke. Jordan Barnett MDTRANSCRIPT
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Stroke Update
Serum Markers for Acute Neurologic Conditions
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Introduction
• Same diagnostic challenges that exist for stroke exist for myocardial infarction
• Technology used in MI now being applied to stroke
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Overview
• >700,000 strokes annually
• 10% of strokes involve intracerebral hemorrhage
• Large proportion of patients die or do badly
• 35-52% of patients die with hemorrhage within 30 days
• Half of deaths occur within 48 hrs
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Risk factors for hemorrhagic Stroke
• Increase with age
• Race (Blacks at least twofold over whites)
• Prior stroke
• Hypertension
• Use of anticoagulant or thrombolytic agents
• Alcohol and/or Cocaine
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Location of intracerebral Hemorrhages
• Lobar
• Putaminal
• Cerebellar
• Intraventricular
• Posterior fossa (require surgery)
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Clinical Features Of hemorrhage
• Headache
• Vomiting
• Seizures
• 82% mental status change
• >75% have hemiplegia or hemiparesis
• 63% have headache
• 22% vomit
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Providing Prognostic data
• Volume of hemorrhage: estimated by using simplified formula ABC/2
• A determined by measuring CT slice with largest diameter of hemorrhage in millimeters
• B determined by measuring largest diameter of hemorrhage 90* to A on Same slice
• C determined by adding number of slices on which hemorrhage seen multiplied by slice thickness
• GCS
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Prognosis
• 91% of patients with bleeding >60 ml and GCS of <=8 die in 30 days
• All patients will bleeding >90 ml die
• 19% of patients with bleeding <= 30 ml and GCS >= 9 die in 30 days
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Hemorrhage growth
• Ongoing process rather than single episode• 38% of patients will have one-third increase in
hemorrhage size in first 24 hrs• Presentation not subtle in most cases• Intraventricular extension significantly increases
morbidity and mortality• 30% of hemorrhages in regions around basal ganglion
expand• Hemorrhages in thalmus expand significantly• Lobar most amenable to therapy
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Lobar Hemorrhage
• Open skull and evacuate blood
• Endoscopic evacuation
• Stereostactics
• No good science, yet sterotactic and endoscopic techniques make most sens in lobar hemorrhage
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Neuronal Markers
• Released from dying and ischemic neurons into cerebrospinal fluid and can be used to diagnose various neurologic emergencies
• May be able to discriminate between patients with reversible vs irreversible events
• Greatest Potential in prehospital setting• Maybe used to identify patients at higher risk for
complications if treated by thrombolytics
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Cardiac Vs Neuronal Markers
• Heart simple homogeneous muscle
• Brain has complex populations of cells (neurons have various functions and distributions and variety of support cells)
• Ideal marker must be able to pass blood-brain barrier
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Markers Under Investigation
• Neuron-specific Enolase
• Structural proteins
• Direct Neuronal Markers
• Myelin Basic protein
• S-100• Thrombomodulin
• D-dimer
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Neuron-specific Enolase
• Cytoplasmic enzyme
• Any small stress allows NSE to egress across cell membrane
• Cell does not need to die to release NSE – It just has to be leaky. Sensitive yet not specific
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Structural Proteins
• Significant injury to cell and enzymatic degradation required before structural proteins found in CSF. More specific yet harder to see in early phases
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Direct Neuronal Markers
• NSE and tau proteins most important
• Complement each other because NSE from cytoplasm and tau from structural molecule
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Myelin basic protein
• Used extensively in multiple sclerosis and other demyelinating disorders as a way to diagnose and predict outcome
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S-100
• Most studied neurolgic marker
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Thrombomodulin
• Most promising for assessing integrity of vascular wall
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D-Dimer
• Not specific but indicates abnormality
• May be used to confirm that activation/coagulation pathway involved, and patients headache not migraine
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C-Reactive Protein
• Used to measure inflammation
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Ideal Marker
• Small molecular size
• Must be sensitive for early ischemia (within 3 hrs)
• Predictable and rapid and accurate
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NSE and tau protein
• Specific for neurons
• NSE also found in red blood cells
• Levels can be falsely elevated if extensive hemolysis present
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Similarities to heart technology
• Since no perfect marker available, variety of markers used as panel of tests to increase sensitivity an specificity
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Statistics
• Stroke leading cause of adult disability
• Patients fear stroke more than heart attack because stroke leaves victims cognitively impaired
• 800,000 new strokes annually
• 85% of strokes ischemic
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Why serum markers for stroke?
• Stroke remains diagnosis of exclusion
• MRI helpfully, but usually cannot be obtained in timely fashion
• CT can be sensitive but not always
• 70% who present weak and dizzy have clinically silent event
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Hemorrhage
• Can be detected on CT
• Diagnostic utility of markers may not be high in this setting, but may help determine which patients at risk for complications and which will extend infarct
• MBP found in deep white matter where hemorrhages usually occur.
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Traumatic brain injury
• Currently have poor tools to determine which patients have had cognitive deficit secondary to concussion and which are at risk for second impact syndrome
• Markers have potential for diagnosing minor head injury
• Markers shown to detect edema in animal modem • Markers very predictive of outcome in patients
with negative head CTS
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Limitations
• Time delay in serum
• Some markers do not cross blood-brain barrier
• No single marker sufficient
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Future
• Goal to have marker by 2010 that will take 5 min and one drop of blood to make diagnosis
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Conclusion
• No markers currently approved by FDA for routine use, although approved for scientific research purposes
• Expect markers in 2-3 years