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Acute Stroke Therapy

Acute Stroke Therapy. Andrew Slivka, MD Associate Professor of Neurology Cerebrovascular Diseases and Stroke The Ohio State University Medical Center. General Early Supportive Care. 1. Early mobilization and measures to prevent aspiration

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Acute Stroke Therapy

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  1. Acute Stroke Therapy Andrew Slivka, MD Associate Professor of Neurology Cerebrovascular Diseases and Stroke The Ohio State University Medical Center

  2. General Early Supportive Care 1. Early mobilization and measures to prevent aspiration *2. Heparin for DVT prophylaxis in immobilized patients, pneumatic compression devices in patients who cannot receive heparin

  3. Treatment of Cerebral Edema *1. Steroids not recommended 2. Osmotherapy, hyperventilation for patients deteriorating due to increased intracranial pressure or with herniation syndromes 3. Surgical decompression, ventricular shunt for large cerebellar infarcts compressing brain stem 4. Surgical decompression for large hemispheric infarct may be life-saving, but may have severe residual neurological deficits

  4. Acute Treatment Antithrombotic Therapy 1. Heparin or LMW heparin when used within 48 hours of acute ischemic stroke do not reduce morbidity, mortality, or rate of stroke reoccurrence, but do increase systemic and CNS bleeding risk independent of stroke subtype 2. Aspirin (160-325mg) within 48 hours

  5. Early Anticoagulation afterCardioembolic Stroke

  6. Acute Stroke Treatment Strategies • Recanalization • Neuroprotection

  7. Recanalization Strategies • Delivery (iv, ia, iv-ia) • Drugs (UK, t-PA, Pro-UK, retaplase, desmoteplase) • Mechanical (wire, balloon, snare, angiojet, MERCI)

  8. Thrombolytic Therapy - iv t-PA NINDS t-PA Stroke Trial • Inclusion Criteria • Age > 18 years • Clearly defined time of onset < 3 hours • Clinical diagnosis of ischemic stroke

  9. Thrombolytic Therapy - iv t-PA • Exclusion Criteria • Suspicion of SAH • Recent intracranial surgery, serious head trauma, recent previous stroke (within 3 months) • History of ICH • Uncontrolled HPT (> 185 mmHg systolic, > 110 mgHg diastolic • Seizure at onset • active internal bleeding • Intracranial neoplasm, AVM, or aneurysm

  10. Thrombolytic Therapy - iv t-PA • Exclusion Criteria - continued • Bleeding diathesis: PT > 15 sec (or INR > 1.7 ) - heparin treatment with elevated PTT, platelet <100,000/mm3 • Major surgery, serious trauma < 2 weeks GI or GU hemorrhage < 3 weeks • Arterial puncture at noncompressable site or LP < 1 week

  11. Thrombolytic Therapy - iv t-PA • Exclusion Criteria - continued • Pregnant • Rapidly improving neurological signs • Isolated mild neurological deficits • Glucose < 50 mg/dl or > 400 mg/dl

  12. NINDS t-PA Stroke Trial: Design • Part I (n=291): half treated within 90 minutes • Primary outcome – complete resolution or > 4 point improvement in NIHSS at 24 hours. • Secondary outcome – minimal or no disability at 3 months • Part II (n= 333): half treated within 90 minutes • Primary outcome – minimal or no disability at 3 months • Dose: 0.9 mg/kg (maximum 90 mg); 10% bolus, remainder infused over 1 hour

  13. Outcome of Patients Treated With t-PA

  14. NIH iv t-PA Trial

  15. Predictors of Outcome with t-PA • Age, deficit severity, diabetes, admission blood pressure, early CT changes, influence outcome, but do not alter likelihood of responding favorably to t-PA • NIHSS > 20: Rankin 0-1(at 3 months) 10% with t-PA, 4% placebo; Rankin 4,5 or 6 is 70%, independent of treatment • Brain edema/mass effect on CT: Rankin 0-1 (at 3 months) 25% with t-PA, 16% placebo; Rankin 4,5 or 6 is 55%, independent of treatment • Time to treatment correlates with outcome

  16. Symptomatic Intracerebral Hemorrhage with t-PA Treatment • NINDS Trial (n=312) 6% • STARS Study (n=389) 3% • CASES Study (n=450) 4% • Average Phase IV Studies 5% (16%) • n=>1400

  17. Risks for Symptomatic Intracerebral Hemorrhage • Hospital size (experience) • Protocol violations • Severity of neurological deficit • Brain edema or mass effect on CT

  18. IV t-PA Use After 3 Hours • Atlantis: 613 patients, 3-5 hours after stroke, NIH > 3 • ECASS II: 800 patients < 6 hours after stroke • 90 day Outcome: Placebo t-PA

  19. Intra-arterial Thrombolysis • Series with t-PA, UK • Pro-urokinase (PROACT II) • 180 patients with proximal MCA occlusion within 6 hours • Recanalization: 66% treated group, 19% control • Good outcome: 40% treated group, 25% control • Symptomatic ICH: 10% treated group, 2% control • Mortality: 25% treated group, 27% control

  20. Intra-arterial Thrombolysis at OSU • 81 patients treated from May 1995 to July 2003 • 52% male, 16% African American, 1% Asian American, Mean age 72 years • 26% with good clinical outcome (mRS < 2) • 70% with recanalization (33% complete) • 7% with symptomatic ICH

  21. Predictors of Clinical Outcome • No occlusion • 38% with good outcome vs. 26% with occlusion, Rx • Age > 80 years • 0/14 with good outcomes (57% recanalize, 29% complete) • Admission NIHSS • Good outcome 11/16 (69%) 4-10 9/48 (19%) 11-20 1/18 (6%) >20

  22. Predictors of Clinical Outcome Time to Treat • < 5 hours – good outcome 15/47 (32%) • Recanalization 77% (41% complete) • > 5 hours – good outcome 6/34 (18%) • Recanalization 62% (24% complete)

  23. Predictors of Clinical Outcome Recanalization • Complete recanalization-13/27 (48%) good outcome • Partial recanalization 7/30 (23%) good outcome • No recanalization 1/24 (4%) good outcome

  24. Predictors of Outcome Collateral Circulation • When complete recanalization – linear relationship between clinical outcome and infarct size and collateral grade • When partial/no recanalization – no correlation with clinical outcome, excellent collateral have smaller infarcts than other collateral grades

  25. Intravenous – Intra arterial • IMS (Stroke, 2004) 80 Patients within 3 hours • 6 mg/kg (max 60 mg) t-PA iv over 30 minutes up to 22 mg t-PA ia over 2 hours if occlusion seen by angiography • Good outcome 30% (32% iv t-PA, 18% control • Symptomatic ICH 6.3% (6.6% iv t-PA, 1% control • Mortality 16% (21% iv t-PA, 24% control)

  26. Mechanical Disruption • Anecdotal: snare, balloon, angio jet • MERCI (Stroke, 2005) • 141 patients with intracranial large vessel occlusion treated within 8 hours • Recanalization: 48% (19% PROACT control) • Complications: 7% (emboli, dissection, SAH) • Good outcome: 28% (46% recanalized, 10% occluded) • Mortality: 43% (32 recanalized, 54% occluded)

  27. Detection of Preservable Brain • MR • DWI • PI • MRA • CT • CTP • CTA

  28. Desmoteplase • 45-60 patients within 9 hours, DWI/PI mismatch • DIAS – Europe, DEDAS – USA, Germany • Dose response found • Reperfusion: 50-70% (vs 20-37% control) • Good outcome: 66% (vs 22-25% control) • No symptomatic ICH

  29. Treatment Algorithms • Less than 3 hours • NIHSS <10 iv t-PA • NIHSS 10 or greater iv/ia t-PA • 3-6 hours • DIAS-II • NIHSS < 10 or lacunar infarct: MR then ia t-PA (? Iv t-PA) • Greater than 6 hours • NIHSS 10 or greater: MR then MERCI

  30. Treatment: Special Populations • Post catheterization • Post operative • Children/adolescents

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