Interventions in Acute Ischemic Stroke: Strategies for the New Millennium

1. Interventions in Acute Ischemic Stroke:Strategies for the New Millennium

2. Clinical Decisions in Emergency MedicinePonte Vedra, FLJune 22-23, 2007

3. David A. Miller M.D.Assistant Professor of RadiologyEndovascular and Therapeutic NeuroradiologyMayo Clinic Jacksonville, FL

4. The Rationale For Acute Stroke Treatment • Stroke is a very common disorder. Estimates there between 700,000 and 750,000 strokes each year in the U.S. Mortality is now over 150,000/year. • A large percentage of these are ischemic. • The lifetime cost of an ischemic stroke is 100,000 or more.

5. The Rationale For Acute Stroke Treatment • Despite improvements in conventional medical therapy the morbidity and mortality rates are close to 17% at 30 days and 40% at 5 years. • In patients with acute MCA occlusion the rate of death or severe disability has been reported at 40 -78%.

6. The Rationale For Acute Stroke Treatment • The treatment of acute ischemic stroke has undergone a tremendous evolution over the past decade or so with the introduction of techniques for early intervention. • This, coupled with advances in diagnostic capability, has allowed for much more aggressive treatment of these patients

7. The Rationale For Acute Stroke Treatment • More than 60% of hospitals in a recent survey did not have stroke protocols in place, and even more did not provide for the rapid identification of stroke patients. • Nationally, less than 5% of patients with ischemic stroke are receiving tPA.

8. Diagnostics • The availability of high quality CT or MRI imaging and immediate quality interpretation is essential for acute stroke care. • Aside from the initial neurologic examination, this is the most important piece of information that you can get.

9. Diagnostics • The CT scan remains the mainstay of diagnostic evaluation of acute stroke. • A non contrast CT scan of the brain is the fastest and most effective way of making the initial evaluation of acute stroke patients.

10. Diagnostics

11. Diagnostics

12. Diagnostics

13. Principles of Acute Stroke Care • It can quickly exclude patients (parenchymal hemorrhage, large infarct, mass) from treatment paradigms and can occasionally quickly include patients (dense artery sign). • Unfortunately, the non contrast CT is relatively insensitive in detecting thrombus.

14. Diagnostics • Non contrast CT is also unable to give much information about the size of the acute lesion or status of the affected tissue. • Newer high speed (spiral) CT scanners can, however, provide this type of information through perfusion imaging and CT angiography.

15. Diagnostics • With time as a primary issue, we follow the non contrast CT with CT perfusion and CTA. • This allows us to get most of the imaging information we need to make treatment decisions in a few minutes.

16. Diagnostics

17. Diagnostics

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19. Diagnostics

20. Principles of Acute Stroke Care • A recent study of 62 patients found that CT angiography failed to show a lesion seen on conventional angiography in only one instance. • These capabilities allow very rapid stratification of the patient into a treatment group.

21. Diagnostics • MRI • Tremendous potential for both anatomic and physiologic evaluation of acute stroke. • Diffusion weighted imaging probably the most sensitive measure of ischemia.

22. Diagnostics • Diffusion/Perfusion mismatch offers the promise of extending the window for treatment. • Problems of cost, availability, and longer time will need to be addressed before this will become widely used in acute stroke.

23. Diagnostics

24. Diagnostics MRA Brain 8:25 PM 4.5 hours out from witnessed stroke. Pt. had anaphylaxis to prior iodine injection

25. The Rationale For Acute Stroke Treatment • Tissue Plasminogen Activator (tPA) has been approved by the FDA for the treatment of acute stroke. Approval has been for intravenous administration within 3 hours of onset of symptoms. • This drug (and others) have been used in several large scale trials of intravenous and intra-arterial thrombolysis in acute stroke.

26. IA tPA Therapy for Acute Stroke • The delivery of thrombolytic agents locally to the site of intracranial thrombus has been used effectively in the treatment of acute stroke. • The method has the advantages of achieving higher local concentration of drug at a lower dose, potentially increasing effectiveness while lowering systemic concentration.

27. IA tPA Therapy for Acute Stroke • Other advantages include: • the possibility of mechanical manipulation of the clot. • the ability to follow the progress of therapy and adjust drug dose to effect. • a greater window for initiating treatment.

28. IA tPA Therapy for Acute Stroke • The method does have some disadvantages as well: • Angiography is required for drug delivery, with the increased risk for complication associated with the procedure (though complication rates for angiography even in this setting are low) • There is an inherent delay in delivering medication.

29. The Studies

30. NINDS tPA Stroke Study (the IV tPA study) • tPA given intravenously at a dose of 0.9 mg/kg (10% as bolus with the remainder infused over 60 minutes). • Initial results showed early improvement in 47% of the treated group vs. 39% of the placebo group. • Good outcomes with tPA were 11-13% higher

31. NINDS tPA Stroke Study • Symptomatic hemorrhage was 6.4% for the treated group vs. 0.6% for the placebo group. • Still mortality at 3 months was 17% for the treated group vs. 21% for the placebo group.

32. IA tPA Therapy for Acute Stroke (Proact II) • Multicenter Randomized Trial (180pts). • Stroke in the MCA distribution, onset <6hrs. • Angiogram demonstrating M1 or M2 occlusion. • 9mg IA pro-urokinase with heparin vs. heparin alone.

33. IA tPA Therapy for Acute Stroke • Pts generally had severe strokes (NIHSS>17). • recanalization rate with pro-UK was 66%. • recanalization rate with heparin alone was 18%. • proportion of patients achieving independence at 90 days (mRS<2) was 40% in UK group vs. 25% in the heparin only group. • Symptomatic ICH 10.9% with UK vs. 3.1% with heparin.

34. Proact (II) • Randomized multicenter trial with 180 patients treated within 6 hours of onset (this required screening over 12,000 patients). • Recanalization rate was 66% (18% control). • Good clinical outcomes at 90 days (mRS<2) were seen in 40% of treated patients vs. 25% of controls. (a 15% absolute benefit and 58% relative benefit)

35. Combined Trials • Several randomized trials comparing i.v. therapy alone v.s. i.v. and i.a. therapy have been conducted. These include the EMS bridging trial(Lewandowski), the IMS trial( Tomsick), and the IA/IV trial (Keris). • These trials generally showed increased rates of recanalization with combined therapy (without significant increased morbidity) and improved outcomes for combined therapy in 2 of the 3 trials.

36. Intracranial Hemorrhage after tPA • Major acute complication of either IV or IA therapy. • Severity of initial deficit, initial CT findings of ischemia, increased dose of thrombolytic, age and increased BP have been suggested as potential risk factors.

37. Intracranial Hemorrhage after tPA • In NINDS, pts with a NIHSS of >20 (severe deficit) were 11 times more likely to develop a symptomatic ICH than pts with a NIHSS of <5 (mild deficit). • The presence of early ischemic changes (hypodensity, gyral edema) on CT, mass effect or brain edema increased the risk of ICH.

38. Intracranial Hemorrhage after tPA • Time is also a factor in ICH. The later treatment is instituted, either with IV or IA therapy, the more likely that ICH will occur. • With IA therapy, increasing dose also increases the ICH risk, though different trials have reported varying rates of increase. Interestingly, ICH is not always symptomatic, and many studies show increased overall benefit despite increased symptomatic hemorrhage.

39. Combined IV and IA Therapy • EMS / IMS • Studies looking at combined therapy with an initial (lower) dose of of iv tPA (0.6 mg/kg) followed by cerebral angiography and IA therapy of any identified thrombus (M1 or M2) • Recanalization was achieved in 67% of pts receiving iv and IA tPA and in 60% of pts receiving placebo and IA tPA

40. MERCI • 80 patients with acute ICA thrombus. • 53% had recanalization with MERCI alone. • 63% had recanalization with MERCI and adjunctive endovascular therapy. • Good clinical outcome @ 90 days: • 39% with recanalization • 3% without recanalization

41. Thrombolysis In The Vertebral Basilar System • Several small series of patients with posterior circulation occlusions have been reported. • In general, the series are not randomized. The majority of patients presented and were treated outside the 3 hr. or even 6 hr. window. • They were almost all treated with pro-UK. • Mortality was high and efficacy is unclear.

42. Principles Of Acute Stroke Care • Designation of appropriate centers and clear plans for delivery of patients will also greatly improve the available population for acute treatment. • The establishment of stroke centers may aid in reducing the time to treatment.

43. Mayo Clinic Jacksonville Stroke Treatment • Mayo Clinic Jacksonville has recently achieved certification by the JCAHO as a Primary Stroke Center.

44. Mayo Clinic Jacksonville Stroke Treatment • Stroke Team consisting of the ER Physician, ER charge nurse, Neurologist on call, CT tech, Neuroradiologist on call, Angiography tech on call, and Radiology nurse on call. • Pharmacy, Laboratory services, and Critical Care Physician all notified ASAP and standing by

45. Mayo Clinic Jacksonville Stroke Treatment • Identification of an acute stroke with potential for intervention triggers a Brain Attack alert. • ER and CT cleared for rapid assessment and imaging. • Patient arrives in ER, is immediately assessed, and blood work is drawn. Large bore iv placed. • If patient meets criteria for brain attack treatment, they are transferred to CT ASAP

46. Mayo Clinic Jacksonville Stroke Treatment • At this point the “Brain attack” team is called. • This includes the ER physician, the Neurology resident on call, and the Neuroradiologist on call. • The idea is that they will meet in the CT scan room (if possible) to review the scan and plan Tx

47. Mayo Clinic Jacksonville Stroke Treatment • Non contrast head CT is performed. • If no hemorrhage (or other exclusion criteria) contrast is injected for CT perfusion and CT angiogram. • Evaluation of imaging performed by Neuroradiology with stroke team, and plan of action is formed.

48. Mayo Clinic Jacksonville Stroke Treatment • In general, the patient is treated with IV tPA, IA tPA, or combination therapy according to the guidelines outlined by recent studies. • Patients may be enrolled in other protocols if eligible. • If patient does not meet criteria for inclusion or if family refuses acute thrombolysis, patient is admitted for conservative care.

49. Acute Stroke • Timing of Therapy: • 1-3 hours – systemic (intravenous tPA) therapy • 1-6 hours – local (intracranial micro catheter) therapy • 1-24 (or more) hours local therapy in the posterior fossa.

50. Mayo Clinic Jacksonville Stroke Treatment • Advantages to Mayo Clinic model in developing a stroke team and center: • Institutional support. • no competing groups. • no financial disincentives or disagreements.