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Who is the man in the picture?

Who is the man in the picture?. Osama Bin Laden Charles Darwin Loui Pasteur Charles Dickens Barack Hussein Obama. In 1869 wrote a letter to W.H. Willis MD, mentioning difficulties speaking and moving “foot”

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Who is the man in the picture?

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  1. Who is the man in the picture? • Osama Bin Laden • Charles Darwin • Loui Pasteur • Charles Dickens • Barack Hussein Obama

  2. In 1869 wrote a letter to W.H. Willis MD, mentioning difficulties speaking and moving “foot” Jan. 1870 new year’s day at Gad’s Hill suffering another attack of …”the foot trouble” Jan 23 complains: “something the matter with my right thumb…and can’t write plainly” June 8th : writing Edwin Drood and suffers a stroke at Dinner. A Journal of the life of Charles Dickens 1869-1870 A.Tamayo U of M

  3. TRANSIENT ISCHEMIC ATTACK A.Tamayo U of M

  4. Transient Ischemic AttackFrom Definition to Treatment Arturo Tamayo MD, FAHA Assistant Professor of Neurology U of M Director of the Stroke Prevention Clinics BRHA and WHSC

  5. Disclosures • Research board member and lecturer to the Heart and Stroke Foundation of Canada. • Member of the Steering Committee of the Canadian Stroke Strategy and Consortium • Speakers Honoraria: Pfizer, Allergan, and Schering-Plough • NO STOCKS in pharmaceutical industry A.Tamayo U of M

  6. TIA and its implications has evolved over the last decade implicating:a) Definition b) Risk stratification c) Acute decision making-management d) Prognosis TIA… The Problem A.Tamayo U of M

  7. What is the definition of TIA? • Transient deficit lasting less than 24 hrs. • Deficit which improves (but not resolves) within 24 hours. • Transient deficit lasting less than 30 min. • Transient deficit lasting up to an hour. • All of the above

  8. TIA: Definition • TIA was defined as an episode of focal, transient neurological deficit of vascular etiology that resolve in less than 24 hrs.NINDS classification of CVD. Stroke 1990; 21:637. • Definition NOT ANYMORE accepted Incorrect and inaccurate • A.Tamayo U of M

  9. TIA: Definition • A.Tamayo U of M

  10. TIA The Incidence and Prevalence • A.Tamayo U of M

  11. NSA sponsored telephone survey A total of 175,000 phone calls Only 8.6% was able to identify symptoms 10,112 participants: 2.3% (95% CI, 2.0-2.6%) had Dx of TIA given by a physician only 64% saw a physician within 24 hrs. 2.3% were diagnosed as Stroke. 19 of them had a previous TIA.3.2% had a TIA but were not seen by a doctor Projecting results to US population: 4.9 million of people have been diagnosed with TIA Univariate analysis:History of TIA was more common in the elderlyThose with lower income Fewer years of education Neurology.2003;60:1429-34 • A.Tamayo U of M

  12. That is: In 2002: 204,000 TIAs in USA • Stroke. 2005;36:720-723. • A.Tamayo U of M

  13. NEW DEFINITION TRANSIENT ISCHEMIC ATTACKTIA is a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with complete resolution of symptoms in less than an hourand without evidence of infarction. NEJM. 2002; 347:1013-1016. • A.Tamayo U of M

  14. Time Based Deficit < 24 hours. Suggests Benign Delays Intervention Inaccurately predicts ischemia. Diverges from CAD tPA- Could be a TIA Tissue Based <1 hr event without evidence of infarction. Indicates potential ischemic danger. Encourage IMAGING and intervention Good ischemic predictor Consistent with CAD tPA- Almost all are stroke TIA old vs. new definition • A.Tamayo U of M

  15. Stroke 1999;30:1174 • A.Tamayo U of M

  16. TIA and its implications has evolved over the last decade implicating:a) Definition b) Risk stratification c) Acute decision making-management d) Prognosis TIA… The Problem • A.Tamayo U of M

  17. Which one of the following is true? • TIA patients are on higher risk of stroke within 3 months • Most of patient with TIA present with a stroke within a week of first event • The risk differs if they have hemispheric or retinal symptoms • They are on high risk of cardiovascular problems • All of the above

  18. Stroke Risk after a TIA Study N Stroke Risk Whisnant, et al 198 10.0%/90d Johnston, et al 1707 10.5%/90d Johnston, et al (Kaiser C) 976 8.4%/90d Eliazsew (NASCET) 603 20.1%/90d Panagos, et al 790 13.3%/90d FASTER (CANADA) 150 25.0%/90d Lovett, (Oxfordshire) 209 12.0%/30d Biller, et al 55 9.1% / 6 d Putman, et al 74 6.8%/6 d Average 13.3% Stroke Risk in 90 Days after TIA • A.Tamayo U of M

  19. The Northern California TIA StudyJAMA.2000:13;284(22):2901-6 • Northern California Keiser district16 hospitals2.9 million coveredRepresentative of the San Francisco Bay • Patients given diagnosis of TIA @ ER.March 1997- Feb 1998.Follow up for record review for 3 months Settings Cohort Study • A.Tamayo U of M

  20. The CohortJAMA 2000:13;284:2901-6 • N= 1707 patients. Mean 72 yo.53% females.Median spell 70 min. • 3 months risk of stroke…… 10.5%1 week risk of stroke ……... 6.0% • Recurrent TIA……………… 13.2% • Cardiovascular hospitaliz… 2.7% • Death……………………….. 2.6% • Any of these events………. 26.2% A.Tamayo U of M

  21. Higher risk of stroke within 7 days A.Tamayo U of M

  22. What did we learn from NASCET and TIA?Eliasziw M. et al. CMAJ 2004;30:170(7)1105-9 A.Tamayo U of M

  23. Age > 60 DM Duration of episode > 10 min Unilateral weakness Speech impairment TIA STRATIFICATIONThe California TIA RISK SCALE A.Tamayo U of M

  24. The California Score A.Tamayo U of M

  25. Risk Stratification with ABCD2*2-day stroke risk: 1%(0-3 points), 4% (4-5 points), 8% (6-7 points)*90 day stroke risk up to 25%Lancet 2007; 369:283-92 A.Tamayo U of M

  26. Defining high risk.ABCD2 + MRI (DWI / intracranial vessel occlusions) Coutts et al. Int J. Stroke 2008; Ann Neurol 2005A. Tamayo U of M

  27. TIA and its implications has evolved over the last decade implicating:a) Definition b) Risk stratification c) Acute decision making-management d) Prognosis TIA… The Problem A.Tamayo U of M

  28. TIA- is an emergency!WHEN SHOULD WE TREAT? Half of all strokes occur in the first 2 days after TIA Gladstone et al. CMAJ 2004A.Tamayo U of M

  29. When to Treat? • 23% of patients with ischemic stroke have had a TIA before their strokea) 17% occur the day of the strokeb) 9% occurred the previous dayc) 43% had a TIA during the 7 days prior • Pooled analysis from population and RCTs (OXCASC, OCSP, UK-TIA and ECST)Rothwell & Warlow, Neurology 2005;64:817 A.Tamayo U of M

  30. ER ASSESSMENT • Points to remember: • ABCD2 score has a sensibility of 80%, that is, there are 20% of patients that can be missed. • This scale was not include patients on Atrial Fibrillation who are on extreme risk! A.Tamayo U of M

  31. 3-Month Stroke Risk According to Etiological subtype • Lovett et al. Neurology 2004: Meta analysis, n=1709 A.Tamayo U of M

  32. Extracranial Vessel Disease A.Tamayo U of M

  33. TCD and Carotid Microemboli A.Tamayo U of M

  34. ANTIPLATELETS A.Tamayo U of M

  35. PLAVIX LOADING DOSE225-300 mg RationaleNOT PROVEN EXPERIENCE IN STROKE PATIENTS. ONE TRIAL ON ITS WAY. However:a) Acute coronary syndromes: Dosages between 200-300mg inhibit in 15 minutes sCD 40 ligand (sCD40L) and CRP (?).b) Better outcome. Am Heart J. 2006; 151(2):521 e1-e4. Cure Study. Am Heart J. 2005;150(6) 1177-85. Circulation 2005.112(19):2946-2950. A.Tamayo U of M

  36. A.Tamayo U of M

  37. Timing of Surgical InterventionThe NASCET and ECST Studies 40 NNT=3 70 to 99% stenosis 30.2 50 to 69% stenosis 30 5-year ARR in stroke (%) NNT=7 20 17.6 14.8 11.4 8.9 10 3.3 4 0 -2.9 -10 0-2 2-4 4-12 >12 Time from event to randomization (weeks) Numbers above bars indicate actual absolute risk reduction. Vertical bars are 95% CIs A.Tamayo U of M • Lancet 2004;363:915-24.

  38. CAROTID STENTING A.Tamayo U of M

  39. CREST TRIAL= CAE • Brott TG. N.Engl J Med 2010;363:498 A.Tamayo U of M

  40. Atrial Fibrillation One of the strongest known independent risk factor for ischemic stroke. Etiology usually divided into valvular and non-valvular disease and into permanent vs. paroxystic. Poorly organized contractions result in sluggish atrial blood flow (> left atrial appendage) favoring thrombus formation. Thrombi composed from deposits of fibrin and platelets.Marder VJ, Chute DJ, Starkman S, et al. Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke 2006:37;2086-2093. A.Tamayo U of M

  41. 2004 ACCP Guidelines for risk stratification and antithrombotic guidelines for NVAF • Chest.2004;126:429S-456S. A.Tamayo U of M

  42. Warfarin vs No treatment Primary Prevention Five major primary prevention trials consistently showed:a) RRR 68% per year.b) NNT 32c) Reduced combined outcome by 48% (stroke, systemic embolism or death) Ezekowitz MD. N Engl J Med.1992;327:1406-1412 Secondary Prevention Secondary stroke prevention RRR by 66% (12% risk in untreated vs 4% treated). NNT 13 No hemorrhagic differences among groups EAFT Study. Lancet. 1993;342:1255-1262 A.Tamayo U of M

  43. Hylek EM. N Engl J Med. 2003;349:1019-1026. A.Tamayo U of M

  44. Stroke or systemic embolism (SSE) Noninferiority Superiority p-value p-value Dabigatran 110 mg vs. warfarin <0.001 0.34 Dabigatran 150 mg vs. warfarin <0.001 <0.001 Margin = 1.46 0.50 0.75 1.00 1.25 1.50 HR (95% CI) Connolly SJ., et al. NEJM published online on Aug 30th 2009. DOI 10.1056/NEJMoa0905561 Dabigatran etexilate is in clinical development and not licensed for clinical use in stroke prevention for patients with atrial fibrillation A.Tamayo U of M

  45. The most important modifiable risk factor (2-5x)Ischemic bleeding,Silent strokes Contributes toLarge vessel diseaseSmall vessel (lacunar)LV dysfunction Treatment reduces risk 40% CHEP: <140/90 (in DM <130/80) Stroke. 2006;37:577-617 Vascular RisksHYPERTENSION A.Tamayo U of M

  46. Vascular Risks • Diabetes: Increases x 2 the risk of Stroke. Highly correlated with HTN, and metabolic syndrome.Treatment reduces microvascular complications>macrovascular. • Cholesterol: Doubles the risk of stroke. Risk for CAD. SPARCL (NNT = 50) A.Tamayo U of M

  47. TIA and its implications has evolved over the last decade implicating:a) Definition b) Risk stratification c) Acute decision making-management d) Prognosis TIA… The Problem A.Tamayo U of M

  48. Phase 1 vs. 2 90 days stroke risk from 10% to 2% Medications started right away Carotid endarterectomy expedited A. Tamayo U of M EXPRESS StudyRothwell et al. Lancet 2007

  49. RECOMMENDATIONS IN THE ER: The Never and Ifs’ rules • NEVER FORGET THE TIA CANADIAN GUIDELINES • Play SAFE! (never play un-safe) • Never discharge If not sure; consult Neurologist on Call! • Never discharge a patient unless mayor risk factors and images have been done. (managing hypertension, hyperglycemia, electrolytes imbalance) and CT of brain and carotid images are available. If severe stenosis consult neurology. • Never discharge a patient with crescendo TIAs • Never discharge a patient with mild deficits (that is a stroke) • Never discharge a patient on Atrial Fib. A.Tamayo U of M

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