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ISCHEMIC STROKE, THROMBOLYSIS & TIA

ISCHEMIC STROKE, THROMBOLYSIS & TIA. Cigarettes and Chocolate Milk. Mark Keezer R3 Neurology August 26 th 2009. Objectives. Background review of stroke Approach to acute ischemic stroke Thrombolysis in acute stroke General management of acute stroke Craniectomy for malignant MCA

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ISCHEMIC STROKE, THROMBOLYSIS & TIA

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  1. ISCHEMIC STROKE, THROMBOLYSIS & TIA Cigarettes and Chocolate Milk Mark Keezer R3 Neurology August 26th 2009

  2. Objectives • Background review of stroke • Approach to acute ischemic stroke • Thrombolysis in acute stroke • General management of acute stroke • Craniectomy for malignant MCA • BP control • Approach to TIA.

  3. Synonyms Abound • Stroke is currently the most preferred term • Cerebrovascular accident (CVA ) • Apoplexy (Gr. Being struck down, to suffer a seizure).

  4. Drowning in a Sea of Strokes • Dr. Charles Miller Fisher • House officers and students learn neurology “stroke by stroke” • >50% of neurological admissions • 50,000 new /year in Canada • 3rd most important cause of death • after heart disease and cancer • Most important cause of adult disability • 30% of survivors require daily assistance.

  5. Stroke Definition • Acute • Focal • Neurologic syndrome • Secondary to vascular pathology (ie cerebrovascular disease) • Exclusions include local pressure effects of aneurysms, vascular headache, CNS vasculitis, elevated ICP... Adams et al. Guidelines for the early management of adults with ischemic stroke. A guideline from the AHA/ASA stroke council… Stroke 2007;38:1655-1711.

  6. Stroke Types Lacunar 20% Thromboembolic 10% SAH 10% Cardioembolic 20% Hemorrhagic 20% Ischemic 80% ICH 10% Unknown 25% Other 5% Foulkes et al. The stroke data bank: design, methods and baseline characteristics. Stroke 1988;19:547-554.

  7. Risk Factors 1/3 • Non-modifiable • Age • Male gender • Ethnicity: African or Asian origin • Family history • Stroke in first degree relative • Genetics • MELAS, CADASIL • Fabry’s disease • Ehler’s Danlos type IV • Pseudoxanthoma elasticum • Dyslipidemias • Vasculopathies • Cardiomyopathies.

  8. Risk Factors 2/3 • Modifiable : • HTN – 4 x • DM – 2 x (4x with HTN) • Smoking – 2 x • Hyperlipidemia – 1.5 x • CAD • Stroke , TIA , stenosis • Drugs (cocaine, amphetamines, heroin, EtOH) • A fib – 5-6 x.

  9. CHADS2 Gage et al. Validation of clinical classification schemes for predicting stroke. Results from the national registry of atrial fibrillation. JAMA 2001;285:2864-2870.

  10. Risk Factors 3/3 • Others: • Thrombophilia • APL antibodies (lupus anticoagulant, anticardiolipin antibodies) • Homocysteine • OCP.

  11. Pathophysiology • The brain is very metabolically active tissue • 15-20% of cardiac output • Normal CBF > 55ml/min/100 g • CBF <23 ml/min/100 g: critical level for impairment of function • CBF <10-12 ml/min/100g: infarction regardless of duration • Complete arrest of flow: • 15 sec: suppression of electric activity • 2-4 min: inhibition of synaptic excitability • 4-6 min: inhibition of electric excitability.

  12. Stroke Syndromes 1/2 ACA MCA (Ant choroidal, Gerstmann) PCA (Alexia without agraphia, Balint, Dejerine-Roussy, Anton) Lacunar (PM, PS, SM, AH, CD and 200 more).

  13. Stroke Syndromes 2/2 • Brain stem syndromes • Midbrain • Weber = PCA = ipsi 3rd, contra plegia • Claude = PCA = contra rubral tremor • Benedikt = PCA = ipsi 3rd, contra plegia and rubral tremor • Pons • Marie-Foix Syndrome = long circumferential = ipsi ataxia, contra plegia & ST • Raymond Syndrome = paramedian branches = ipsi 6th, contra plegia • Millard-Gubler Syndrome (aka Foville) = paramedian branches = ipsi 6th& 7th contra plegia • Medulla • Dejerine = vertebral = ipsi 12th, contra plegia and ML • Wallenberg = PICA > vertebral = ipsi 5th, 8th, 9 & 10th, Horner’s and ataxia; contra ST + singultus.

  14. “Code Stroke!” Now what?

  15. ER Evaluation 1/2 • Immediate response! • ABC and G (glucose) • Concise but pertinent history: • WHEN WAS THE PATIENT LAST (& DEFINITELY) SEEN NORMAL ? • Resetting the clock? • Atypical features H/A, NECK PAIN, SZ • Any improvement.

  16. Beware of Mimics! Adams et al. Guidelines for the early management of adults with ischemic stroke. A guideline from the AHA/ASA stroke council… Stroke 2007;38:1655-1711.

  17. ER Evaluation 2/2 • Pertinent PMHx • Risk factors • Dr Minuk’s “5 Horseman of the Apocalypse” • Recent MI, trauma, surgery, migraines, epilepsy or pregnancy • Pertinent Medx • Anticoagulants • Antiplatelets • Antihypertensives • Hypoglycemics / insulin. Albrecht Dürer, Four Horsemen of the Apocalypse, 1498.

  18. Φ Vitals (including glucose) Dr Côté checks the BP in both arms Pulse(s) Cardiac murmurs or carotid bruits.

  19. NINDS Stroke Scale

  20. NINDS Stroke Scale

  21. Requisite Initial Interventions • Would this pt benefit from IV NS? • Dr Wein doesn’t hesitate to give 120cc/hr • Consider a NS Bolus if hypotensive • Maintain fiO2 ≥92%.

  22. Requisite Initial Investigations • CBC • INR • SMA7 (incl glucose) • EKG, troponin • +/- CXR (very modest value and can the pt afford the delay?) • Selected patients: toxicology, b-HCG. Adams et al. Guidelines for the early management of adults with ischemic stroke. A guideline from the AHA/ASA stroke council… Stroke 2007;38:1655-1711.

  23. Neuro-imaging in Acute Stroke

  24. Immediate Goal • Exclude hemorrhage • Exclude mass lesions • Assess location & degree of brain injury • +/- CTA protocol to identify occluded vessel.

  25. First Step • CT scan: • Non-contrast • Goal is door-to-CT in 25 mins • Subtle signs (82% of large vessel occlusions within 6 hrs) • Loss of gray-white matter differentiation • Sulcal effacement • Obscuration of basal ganglia, insula • MCA sign (M1 branch), dot sign (M2/M3 branch) • Parenchymal hypodensity.

  26. ASPECTS: Alberta Stroke Programme Early CT Score • Quantitative alternative to 1/3 MCA exclusion criterion for rt-PA (greater sensitivity and specificity for poor outcome) • Normal: 10 points; -1 point for each area of hypoattenuation or focal swelling • Increased disability ≤ 7. Barber et al. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. Lancet 2000;355:1670-1674.

  27. Thrombolysis!

  28. Indications for rt-PA • Intravenous may be given within 4.5 hours of symptom onset • Intra-arterial may be given within 6 hours under the care of a stroke neurologist • Intra-arterial may be given within 24 hours (or more?) for catastrophic posterior fossa event • AHA guidelines • Do not wait for platelets or INR unless you suspect a possible bleeding diathesis. Adams et al. Guidelines for the early management of adults with ischemic stroke. A guideline from the AHA/ASA stroke council… Stroke 2007;38:1655-1711.

  29. AHA Guideline Criteria 1/2 Adams et al. Guidelines for the early management of adults with ischemic stroke. A guideline from the AHA/ASA stroke council… Stroke 2007;38:1655-1711.

  30. AHA Guideline Criteria 2/2 Adams et al. Guidelines for the early management of adults with ischemic stroke. A guideline from the AHA/ASA stroke council… Stroke 2007;38:1655-1711.

  31. 1/3 of MCA rule Von Kummer et al. Acute stroke: usefullness of early CT findings before thrombolytic therapy. Radiology 1997;205:327-333.

  32. ASPECTS: Alberta Stroke Programme Early CT Score • Quantitative alternative to 1/3 MCA exclusion criterion for rt-PA (greater sensitivity and specificity for poor outcome) • Normal: 10 points; -1 point for each area of hypoattenuation or focal swelling • Increased disability ≤ 7. Barber et al. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. Lancet 2000;355:1670-1674.

  33. ASPECTS: Alberta Stroke Programme Early CT Score • Increased death & disability if ASPECTS ≤ 7 • Increased death & disability if initial NIHSS >15. Barber et al. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. The Lancet 2000;355:1670-1674.

  34. NINDS rt-PA Stroke Study Group • Randomized, double-blind, placebo controlled trial • Included only patients within 3h • Permuted block randomization • Half within 90 minutes • Half between 90-180 minutes • Strict exclusion criteria • No stroke severity criteria • No ischemic size criteria • No myocardial infarction criteria. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM 1995;333:1581-1587.

  35. NINDS rt-PA Stroke Study Group • 2 parts • Part 1: early improvement • 291 pts randomized to rt-PA or placebo • Looked at NIHSS improvement ≥4 pts at 24h • Part 2 : delayed improvement • 333 pts randomized to rt-PA or placebo • Primary outcome: pts with minimal or no deficits at 3 months • 95 or 100 on Barthel index • ≤1 on NIHSS • ≤ 1 on mRS • 1 on Glasgow outcome scale. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM 1995;333:1581-1587.

  36. NINDS rt-PA Stroke Study Group 12% absolute risk reduction at 3 months NNT = 8 NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM 1995;333:1581-1587.

  37. NINDS rt-PA Stroke Study Group 5.9% absolute risk increase at 36 hours NNH = 17 NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM 1995;333:1581-1587.

  38. rt-PA Arithmetic • For every 4 pts with improved outcome at 3 months • 2 pts will suffer symptomatic HT within 36 hrs • 1 of whom will die • A trend towards decreased mortality among treatment group. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM 1995;333:1581-1587.

  39. Cochrane Review rt-PA versus control; Outcome = death or dependency at the end of follow up; patients randomised within 3 hours of stroke. Wardlaw et al. Thrombolysis for acute ischaemic stroke. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD000213. DOI: 10.1002/14651858.CD000213

  40. European Cooperative Acute Stroke Study (ECASS) III • Randomized, double-blind, placebo controlled trial • rt-PA from 3 to 4.5 hrs • Primary outcome was mRS at 3 months • Favourable outcome ≤1 • Exclusion criteria included: • Severe stroke (NIHSS ≥25 or ≥1/3 MCA territory) • Combination of previous stroke and diabetes mellitus. Hacke et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. NEJM 2008;359:1317-1329.

  41. European Cooperative Acute Stroke Study (ECASS) III 7.2% absolute risk reduction at 3 months NNT = 14 Hacke et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. NEJM 2008;359:1317-1329.

  42. European Cooperative Acute Stroke Study (ECASS) III 4.4% absolute risk increase at 3 months NNH = 23 Hacke et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. NEJM 2008;359:1317-1329.

  43. Time is Brain! “Remember that time is money.” Benjamin Franklin, Advice to a Young Tradesman (1748) Saver JL. Time is brain – quantified. Stroke 2006;37:263-266.

  44. Time is Brain! The ATLANTIS, ECASS, and NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. The Lancet 2004;363:768-774.

  45. PROACT II (JAMA 1999) Pro-urokinase in MCA occlusion @ < 6hrs 180 patients (121 tx; 59 placebo) ARR 15% but a further 8% with ICH at 24hrs Intra-arterial may result in greater rates of recanalization (66%!?) Intravenous remains favoured due to potential delays in delivery. Intra-arterial vs. Intravenous Adams et al. Guidelines for the early management of adults with ischemic stroke. A guideline from the AHA/ASA stroke council… Stroke 2007;38:1655-1711.

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