1. Intra - Arterial Thrombolysis for acute stroke
Jeanne Teitelbaum md
Associate Professor
Neurology and Critical Care

2. Intra - Arterial Thrombolysis
Effect on recanalisation
Effect on clinical outcome
Risks
?? Indications

3. Why consider IAT IV rt-PA: Limited to < 3H
Clear but limited clinical benefit
Rate of recanalisation (doppler):
Complete: 32%
Partial or none 68%: 67% MCA, 25% BA, no ICA
(Christou et al 2001)

4. Why consider IAT Persistent obstruction persistent deficit
Increase the therapeutic window
Post-operative stroke
Reduce hemorrhagic complications

5. I.A.T. Theoretical Advantages
Higher concentrations delivered to the clot
Gentle mechanical disruption of the clot
Precise imaging of anatomy, pathology and collateral pattern
Exact degree and timing of recanalisation

6. I.A.T. Potential Disadvantages
Catheter manipulation
Systemic heparinisation
Delay in initiation of thrombolysis
Skilled facilities

7. Intra-arterial Thrombolysis
The Evidence

8. Anterior Circulation

9. PROACT II Trial First phase III trial of I.A.T.
Pro-UK + heparin vs IV heparin within 6h.
180 patients, M1 or M2 MCA occlusion.
Average NIHSS 17.
Median time to I.A.T 5.7 hours.

10. PROACT II Trial mRS < 2 : 40% VS 25% (+- SIG)
Recanalisation at 2h: 66% vs 18%
Hemorrhage at 36h:
all: 46% vs 16%
symptomatic: 10% vs 2%
No difference in mortality

11. I.A.T. Rate of Recanalisation Depends on site and type of occlusion
PROACT II :66% overall
Urbach et al 2002:
Thrombus 53%: 23% carotid T,
74% distal M1
60% M2

13. I.A.T. Rate of Recanalisation Depends on site and type of occlusion
Urbach et al 2002:
Embolus 59% overall
1of 6 with cardiac thrombus
15 of 19 (79%) without thrombus

14. I.A.T. Therapeutic Window
PROACT II: 6h
Arnold et al stroke 2002: 100 pts
Urokinase, MCA, NIH = 14
Average 236 minutes
Recanalisation: 76%
Outcome: excellent 47%, good 21%, poor 22%, dead 10%, hemorrhage 7%

15. I.A.T. Therapeutic Window
Evidence that TTT influences outcome
New studies in progress: 1.5 to 6 h.

16. MRI data Kidwell et al Ann Neurol 2000 7 patients
DWI and PWI pre and post I.A.L.
DWI 3 and 9 h post recanalisation
delayed re of DWI at 7 days
Final volume 86% of original pre - lysis

17. IV plus IA thrombolysis Stroke Bridging Trial
Lewandowski CA et al Stroke 1999
Randomized pilot study. 35 patients
tPA IV 0.6 mg/Kg then IA 20 mg
Symptomatic hemorrhage: 11% both groups
Recanalisation at 2h:
All: 55% IV/IA vs 10% IA
M1: 100% IV/IA vs 67% (PROACT)

18. IV plus IA Thrombolysis Ernst et al Stroke 2000
Continuation of the bridging trial
20 patients
Anterior circulation CVA, NIHSS > 10, planned tPA within 3H
Same dose and method of administration

19. IV plus IA Thrombolysis Ernst et al Stroke 2000
Results:
Initial NIHSS: 11 to 31 (median 21)
IV tPA: median 2H (1H12min to 4H 10 min)
IA tPA: median 3H 30 min

20. IV plus IA Thrombolysis Ernst et al Stroke 2000
Recanalisation: 69%
Heparin bolus in 11patients, infusion in 7
4 hemorrhages, 1 sympt
10 of 16 patients mRS 0-2.
No change in 90d mortality

21. IV plus IA Thrombolysis Zaidat et al Stroke 2002
207 pts thrombolysed from
IA or IV + IA
101 had angio
18 ipsilateral distal ICA occlusion

22. IV plus IA Thrombolysis Zaidat et al Stroke 2002
No difference between groups for:
Recanalisation (70%)
Outcome: mRS % in survivors
Sympt hemorrhage (15-20%)
Mortality: 50% !!

23. I.A.T. Post-Operative Period
Chalela et al, Stroke 2001
Retrospective, median time to stroke 21h
Median TTT: 4.5h (1 to 8h)
tPA or UK
36 patients, 3 major bleeds, 2 post craniotomy, all fatal Minor bleed 25%

24. Posterior Circulation

25. Vertebrobasilar Thrombosis
Life-threatening event: mortality 75-86%
No effective therapy
Heparin: accepted but unproven
Some authors reporting success with IAT:
Retrospective
Small groups

26. Vertebrobasilar I.A.T. Time frame: 1 to 48 h after last progression
Most patients present h after onset
Only 3 studies with > 10 patients

27. Vertebrobasilar I.A.T.
Cohort mortality is decreased compared to historic controls when successful thrombolysis has been achieved.
Benefit even 24 h after presentation.

28. Vertebrobasilar I.A.T. 4 major series
Average time to therapy: up to 24h
Mortality: %, 54%, 67%, 75%
Recanalization: 75%, 71%, 54%, 75%
Hemorrhage: 7%, 0%, 9%, 15%
Rethrombosis: %, %
Recanalized mortality: 26% to 30%

29. Vertebrobasilar I.A.T. Factors affecting outcome
Infarction of a critical amount of brainstem tissue
Coma and quadriparesis at presentation
Lack of recanalization, rethrombosis

30. Possible Conclusions

31. I.A.T. Anterior Circulation
The lack of recanalization is linked to poor outcome.
Better rate of recanalization: 70 vs 34%.
Likely better effect on outcome than IV tPA
Larger therapeutic window (6h),
Can be given post-operatively (except post craniotomy)

32. I.A.T. Anterior Circulation
Combined IV-IA: may be as good or better than IA alone. Can be started faster.
Hemorrhage rates 7 – 10%
Drawbacks: technique, time to initiation, dose variation.

33. I.A.T. Vertebrobasilar system
No satisfactory studies.
Very grim prognosis
I.A.T. only life-saving therapy available
Beneficial effect on mortality and morbidity with recanalization

34. I.A.T. Vertebrobasilar system
Up to 24h after deterioration, up to 48h after onset.
Less benefit if coma, quadriparesis, large area of infarct pre-treatment.

35. ?? Indications

36. Indications in Anterior Circulation
Persistent occlusion post IV tPA < 3h
Within 6 h, but time to treatment is correlated with outcome.
IV contra-indicated with evidence of viable tissue: post-op, > 3H
tPA 9 to 40 mg (med 21)
UK 40,000 – 1,500,000 (med 500,000)

37. Indications in Posterior Circulation
Worsening symptomatology despite heparin
Visualized occlusion
Up to 24h after onset of worsening
UK 250, ,000 per H x 2 then 250,000u per H x 4. With heparin.
tPA: less well studied.