Stroke Update Serum Markers for Acute Neurologic Conditions
Introduction <ul><li>Same diagnostic challenges that exist for stroke exist for myocardial infarction </li></ul><ul><li>Te...
Overview <ul><li>>700,000 strokes annually </li></ul><ul><li>10% of strokes involve intracerebral hemorrhage </li></ul><ul...
Risk factors for hemorrhagic Stroke <ul><li>Increase with age </li></ul><ul><li>Race (Blacks at least twofold over whites)...
Location of intracerebral Hemorrhages <ul><li>Lobar </li></ul><ul><li>Putaminal </li></ul><ul><li>Cerebellar  </li></ul><u...
Clinical Features Of hemorrhage <ul><li>Headache </li></ul><ul><li>Vomiting </li></ul><ul><li>Seizures </li></ul><ul><li>8...
Providing Prognostic data <ul><li>Volume of hemorrhage: estimated by using simplified formula ABC/2 </li></ul><ul><li>A de...
Prognosis <ul><li>91% of patients with bleeding >60 ml and GCS of <=8 die in 30 days </li></ul><ul><li>All patients will b...
Hemorrhage growth <ul><li>Ongoing process rather than single episode </li></ul><ul><li>38% of patients will have one-third...
Lobar Hemorrhage <ul><li>Open skull and evacuate blood </li></ul><ul><li>Endoscopic evacuation </li></ul><ul><li>Stereosta...
Neuronal Markers <ul><li>Released from dying and ischemic neurons into cerebrospinal fluid and can be used to diagnose var...
Cardiac Vs Neuronal Markers <ul><li>Heart simple homogeneous muscle </li></ul><ul><li>Brain has complex populations of cel...
Markers Under Investigation <ul><li>Neuron-specific Enolase </li></ul><ul><li>Structural proteins </li></ul><ul><li>Direct...
Neuron-specific Enolase <ul><li>Cytoplasmic enzyme </li></ul><ul><li>Any small stress allows NSE to egress across cell mem...
Structural Proteins <ul><li>Significant injury to cell and enzymatic degradation required before structural proteins found...
Direct Neuronal Markers <ul><li>NSE and tau proteins most important </li></ul><ul><li>Complement each other because NSE fr...
Myelin basic protein <ul><li>Used extensively in multiple sclerosis and other demyelinating disorders as a way to diagnose...
S-100  <ul><li>Most studied neurolgic marker </li></ul>
Thrombomodulin <ul><li>Most promising for assessing integrity of vascular wall </li></ul>
D-Dimer <ul><li>Not specific but indicates abnormality </li></ul><ul><li>May be used to confirm that activation/coagulatio...
C-Reactive Protein <ul><li>Used to measure inflammation </li></ul>
Ideal Marker <ul><li>Small molecular size </li></ul><ul><li>Must be sensitive for early ischemia (within 3 hrs) </li></ul>...
NSE and tau protein <ul><li>Specific for neurons </li></ul><ul><li>NSE also found in red blood cells </li></ul><ul><li>Lev...
Similarities to heart technology <ul><li>Since no perfect marker available, variety of markers used as panel of tests to i...
Statistics <ul><li>Stroke leading cause of adult disability </li></ul><ul><li>Patients fear stroke more than heart attack ...
Why serum markers for stroke? <ul><li>Stroke remains diagnosis of exclusion </li></ul><ul><li>MRI helpfully, but usually c...
Hemorrhage <ul><li>Can be detected on CT </li></ul><ul><li>Diagnostic utility of markers may not be high in this setting, ...
Traumatic brain injury <ul><li>Currently have poor tools to determine which patients have had cognitive deficit secondary ...
Limitations <ul><li>Time delay in serum </li></ul><ul><li>Some markers do not cross blood-brain barrier </li></ul><ul><li>...
Future <ul><li>Goal to have marker by 2010 that will take 5 min and one drop of blood to make diagnosis </li></ul>
Conclusion <ul><li>No markers currently approved by FDA for routine use, although approved for scientific research purpose...
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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

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

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

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