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Acute Stroke
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  1. Acute Stroke The Basics It’s Not Just t-PA

  2. Nina T. Gentile, MDAssociate ProfessorDepartment of Emergency MedicineTemple University Hospital & School of MedicinePhiladelphia, PA Nina T. Gentile, MD, FAAEM

  3. Stroke Basics • How important is blood pressure control? • How do early ischemic changes on CT impact on decision-making and treatment? • What roles do aspirin and heparin play? • Is hyperglycemia really a problem? • What are the indications for immediate transfer?

  4. Case Example • 72-year-old woman • History: hypertension, diabetes • Sudden slurred speech, left facial droop, left-sided weakness • Family calls 911

  5. Case Example • ACLS squad dispatched, evaluates, transports patient to nearest ED • En route the squad notifies the receiving hospital of a possible stroke patient • And asks….

  6. “Hey Doc… How About Aspirin?” “Isn’t it… …the sooner the better?” Nina T. Gentile, MD, FAAEM

  7. Aspirin in Stroke Meta-Analysis • 41,399 subjects • Nine trials • For every 1,000 patients… …7 fewer early recurrent strokes …13 fewer dead or dependent at 6 months …~ 2 intracerebral bleeds

  8. Aspirin Trials for Stroke • International Stroke Trial (IST) • Chinese Acute Stroke Trial (CAST) • Treatment within 48 hours • IST time to treatment: 19 hours • CAST time to treatment: 25 hours

  9. International Stroke Trial • 19,435 patients • 300 mg/d aspirin within 48 hours of stroke onset • Slightly fewer deaths at 14 days: 9.0% vs 9.44%, p=.02, NNT =91

  10. 0.8% 3.9% 0.9% 2.8% IST – 14 DAY OUTCOME Hemorrhagic 5 Ischemic 4.5 p=.05 4 3.5 3 2.5 2 p=.05 1.5 1 0.5 0 Aspirin Avoid Aspirin

  11. 38.8% 36.5% IST – 6 MONTH OUTCOME Dead or Dependent 40 38 36 34 32 p=.05 30 28 26 24 22 20 Aspirin Avoid Aspirin

  12. Chinese Acute Stroke Trial • 21,106 patients • 160 mg/d dose within 48 hours of stroke onset • Primary end points: • Death at 4 weeks • Death or dependence at discharge

  13. Chinese Acute Stroke Trial Recurrent Stroke 8 4-wk Mortality 7 6 p=.01 5 2.1 1.6 4 3 p=.04 2 3.9 3.3 1 0 Aspirin Avoid Aspirin

  14. Chinese Acute Stroke Trial Dead or Dependent 36 34 32 30 28 p=.08 26 31.6% 30.5% 24 22 20 Aspirin Avoid Aspirin

  15. Aspirin in Acute Stroke: <6 Hours • Not studied •  ICH when used with lytic • Early thrombolytic trials • Phase IV trials

  16. Thrombolysis: Early Studies • ASK (1996): SK or Placebo plus ASA within 4 hours of symptom onset

  17. Thrombolysis: Early Studies • MAST- I (1995): within 6 hours of symptom onset • streptokinase, • aspirin, • both or • neither

  18. Thrombolysis: MAST-I *OR 3.5; 95% CI 1.9-6.5; 2p < 0.00001

  19. Phase IV: IV t-PA in Stroke The Cleveland Area Experience • Symptomatic ICH: 15.7% • Protocol violation: 50% • Received aspirin within 24 hours: 37%

  20. Phase IV: IV t-PA in Stroke STARS 2000 • Symptomatic ICH: 3.3% • Asymptomatic ICH: 8.2% • Protocol violation in 33% • rt-PA >180 minutes: 13% • Received aspirin or anticoagulant within 24 hours: 9%

  21. Aspirin in Acute Stroke • Recommendation: 160 to 325 mg/day within 24 to 48 hours • Avoid in potential candidates for thrombolytic therapy • Delay for at least 24 hours after the administration of rt-PA • Do not administer prehospital (i.e. pre-CT)

  22. Our Patient Arrives… • Right gaze preference • Left face droop • Dysarthria • Left arm paresis • Mild left side neglect

  23. Three Questions… • Is this a stroke? • How would you quantify or describe the stroke? • Would you give t-PA?

  24. Intracerebral hemorrhage Hypoglycemia Hyperglycemia Seizure Migraine headache Hypertensive crisis Tumor Meningitis Encephalitis Brain abscess Differential Diagnosis

  25. ‘Misdiagnosis of Stroke’ • 821 patients admitted to acute stroke unit • 108 (13%) incorrect diagnosis • Seizure: 39% • Confusional states, syncope: 24% Lancet. 1982 Feb 6;1(8267):328-31

  26. Stroke Mimics: Libman 1995 • Evaluator: stroke team • Studies: history, physical • Misdiagnosis: 19% • Mimics identified: seizure, infection, tumor, metabolic, positional vertigo, cardiac syncope, subdural, C- spine fracture, transient amnesia, conversion disorder, MS, myasthenia gravis, parkinsonism, hypertensive encephalopathy

  27. Stroke Mimics: Kothari 1995 • Evaluator: emergency physician • Studies: history, physical, CT • Misdiagnosis: 4% • Mimics identified: paresthesia, seizure, migraine, neuropathy, psychogenic, others

  28. Stroke Mimics: Allder 1999 • Evaluator: neurologist • Studies: history, physical, CT • Misdiagnosis: 9% • Mimics identified: metabolic, migraine, conversion disorder, withdrawal

  29. Stroke Mimics: Ay 1999 • Evaluator: neurologists • Studies: history, physical, CT • Misdiagnosis: 1.2% • Mimics identified: seizure, migraine, tumor, transient global amnesia

  30. NIH Stroke Scale (NIHSS) • Designed as research tool • Widely used in clinical practice • Good interobserver reliability • Helps predict outcome

  31. NIH Stroke Scale (NIHSS) • Helps assess risk of hemorrhage after t-PA treatment • Provides quantitative mechanism for following individual patient

  32. Item Description Range Pt score 1a Level of consciousness 0-3 1 1b LOC Questions 0-2 1 1c LOC Commands 0-2 1 2 Best Gaze 0-2 1 3 Best Visual 0-3 0 4 Facial Palsy 0-3 2 5 Motor Arm Left 0-4 3 6 Motor Arm Right 0-4 0 Our Patient’s NIHSS Score (Part 1)

  33. Item Description Range Pt score 7 Motor Leg Left 0-4 1 8 Motor Leg Right 0-4 0 9 Limb Ataxia 0-2 0 10 Sensory 0-2 1 11 Neglect 0-2 1 12 Dysarthria 0-2 1 13 Best Language 0-3 0 Our Patient’s NIHSS Score (Part 2) Total = 13

  34. Would you Give t-PA? • Potential Benefit • Potential Risks • Exclusion Criteria • Historical features • CT findings

  35. IV t-PA: Potential Benefit • 2775 patients in 6 trials Lancet. 2004

  36. IV t-PA for Stroke: Meta-analysis Stroke. 2005

  37. (NIHSS<1) 25 20 15 10 5 0 t-PA placebo Complete Resolution in 24 Hours

  38. t-PA Placebo NINDS 1 Year Follow-up 80 70 60 50 Favorable Outcome 40 30 20 10 0 <9 10-14 15-20 >20 Presenting NIHSS Score

  39. IV t-PA: Potential Risk • Intracranial hemorrhage • Pooled analysis of 2775 patients treated within 6 hours of sx onset • rt-PA: 82 (5.9%) • Placebo:15 (1.1%)

  40.  Bleeding Risk Active GI or GU bleeding Bleeding Diathesis PLT < 100K INR > 1.7  PTT Potential Major Bleeding Site  BP sys>185, dias >110 Stroke Mimic BS < 50, > 400 Seizure at onset Rapidly improving or minor symptoms Clinical Exclusion Criteria

  41. CT Exclusion Criteria: Blood

  42. Early Ischemic Changes • Loss of insular ribbon • Loss of gray-white interface • Loss of sulci • Acute hypo density • Mass effect • Dense MCA sign

  43. Insular Cortex Sylvian Fissure Early Ischemic Changes

  44. Early Ischemic Changes • Loss of insular ribbon • Loss of gray-white interface • Loss of sulci • Acute hypo density • Mass effect • Dense MCA sign

  45. Early Ischemic Changes • Loss of insular ribbon • Loss of gray-white interface • Loss of sulci • Acute hypo density • Mass effect • Dense MCA sign

  46. Early Ischemic Changes • Loss of insular ribbon () • Loss of gray-white interface () • Loss of sulci ( ) • Acute hypodensity • Mass effect • Dense MCA sign

  47. Early Ischemic Changes • Loss of insular ribbon • Loss of gray-white interface • Loss of sulci • Acute hypodensity • Mass effect • Dense MCA sign

  48. Early Ischemic Changes • Loss of insular ribbon • Loss of gray-white interface • Loss of sulci • Acute hypo density • Mass effect • Dense MCA sign

  49. Would You Give t-PA to Our Patient? “No hemorrhage… …large area of hypoattenuation with edema….”

  50. Review the Facts