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Stroke Update Serum Markers for Acute Neurologic Conditions,  Jordan Barnett MD
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Stroke Update Serum Markers for Acute Neurologic Conditions, Jordan Barnett MD

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2007 Lecture for residents regarding serum markers for CVA/Stroke. Jordan Barnett MD

2007 Lecture for residents regarding serum markers for CVA/Stroke. Jordan Barnett MD

Published in: Health & Medicine

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  • 1. Stroke Update Serum Markers for Acute Neurologic Conditions
  • 2. Introduction
    • Same diagnostic challenges that exist for stroke exist for myocardial infarction
    • Technology used in MI now being applied to stroke
  • 3. 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
  • 4. 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
  • 5. Location of intracerebral Hemorrhages
    • Lobar
    • Putaminal
    • Cerebellar
    • Intraventricular
    • Posterior fossa (require surgery)
  • 6. Clinical Features Of hemorrhage
    • Headache
    • Vomiting
    • Seizures
    • 82% mental status change
    • >75% have hemiplegia or hemiparesis
    • 63% have headache
    • 22% vomit
  • 7. 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
  • 8. 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
  • 9. 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
  • 10. Lobar Hemorrhage
    • Open skull and evacuate blood
    • Endoscopic evacuation
    • Stereostactics
    • No good science, yet sterotactic and endoscopic techniques make most sens in lobar hemorrhage
  • 11. 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
  • 12. 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
  • 13. Markers Under Investigation
    • Neuron-specific Enolase
    • Structural proteins
    • Direct Neuronal Markers
    • Myelin Basic protein
    • S-100 
    • Thrombomodulin
    • D-dimer
  • 14. 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
  • 15. 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
  • 16. Direct Neuronal Markers
    • NSE and tau proteins most important
    • Complement each other because NSE from cytoplasm and tau from structural molecule
  • 17. Myelin basic protein
    • Used extensively in multiple sclerosis and other demyelinating disorders as a way to diagnose and predict outcome
  • 18. S-100 
    • Most studied neurolgic marker
  • 19. Thrombomodulin
    • Most promising for assessing integrity of vascular wall
  • 20. D-Dimer
    • Not specific but indicates abnormality
    • May be used to confirm that activation/coagulation pathway involved, and patients headache not migraine
  • 21. C-Reactive Protein
    • Used to measure inflammation
  • 22. Ideal Marker
    • Small molecular size
    • Must be sensitive for early ischemia (within 3 hrs)
    • Predictable and rapid and accurate
  • 23. NSE and tau protein
    • Specific for neurons
    • NSE also found in red blood cells
    • Levels can be falsely elevated if extensive hemolysis present
  • 24. Similarities to heart technology
    • Since no perfect marker available, variety of markers used as panel of tests to increase sensitivity an specificity
  • 25. 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
  • 26. 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
  • 27. 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.
  • 28. 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
  • 29. Limitations
    • Time delay in serum
    • Some markers do not cross blood-brain barrier
    • No single marker sufficient
  • 30. Future
    • Goal to have marker by 2010 that will take 5 min and one drop of blood to make diagnosis
  • 31. Conclusion
    • No markers currently approved by FDA for routine use, although approved for scientific research purposes
    • Expect markers in 2-3 years