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Intra - Arterial Thrombolysis for acute stroke . Jeanne Teitelbaum md Associate Professor Neurology and Critical Care. Intra - Arterial Thrombolysis. Effect on recanalisation Effect on clinical outcome Risks ?? Indications. Why consider IAT. IV rt-PA: Limited to < 3H

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intra arterial thrombolysis for acute stroke

Intra - Arterial Thrombolysisfor acute stroke

Jeanne Teitelbaum md

Associate Professor

Neurology and Critical Care

intra arterial thrombolysis
Intra - Arterial Thrombolysis
  • Effect on recanalisation
  • Effect on clinical outcome
  • Risks
  • ?? Indications
why consider iat
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)

why consider iat4
Why consider IAT
  • Persistent obstruction persistent deficit
  • Increase the therapeutic window
  • Post-operative stroke
  • Reduce hemorrhagic complications
i a t theoretical advantages
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
i a t potential disadvantages
I.A.T. Potential Disadvantages
  • Catheter manipulation
  • Systemic heparinisation
  • Delay in initiation of thrombolysis
  • Skilled facilities
proact ii trial
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.
proact ii trial10
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
i a t rate of recanalisation depends on site and type of occlusion
I.A.T. Rate of RecanalisationDepends on site and type of occlusion
  • PROACT II :66% overall
  • Urbach et al 2002:

Thrombus 53%: 23% carotid T,

74% distal M1

60% M2

i a t rate of recanalisation depends on site and type of occlusion13
I.A.T. Rate of RecanalisationDepends on site and type of occlusion
  • Urbach et al 2002:
    • Embolus 59% overall

1of 6 with cardiac thrombus

15 of 19 (79%) without thrombus

i a t therapeutic window
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%
i a t therapeutic window15
I.A.T. Therapeutic Window
  • Evidence that TTT influences outcome
  • New studies in progress: 1.5 to 6 h.
mri data kidwell et al
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
iv plus ia thrombolysis stroke bridging trial
IV plus IA thrombolysisStroke 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)
iv plus ia thrombolysis ernst et al stroke 2000
IV plus IA ThrombolysisErnst 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
iv plus ia thrombolysis ernst et al stroke 200019
IV plus IA ThrombolysisErnst 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
iv plus ia thrombolysis ernst et al stroke 200020
IV plus IA ThrombolysisErnst 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
iv plus ia thrombolysis zaidat et al stroke 2002
IV plus IA ThrombolysisZaidat et al Stroke 2002
  • 207 pts thrombolysed from 1995-2000
  • IA or IV + IA
  • 101 had angio
  • 18 ipsilateral distal ICA occlusion
iv plus ia thrombolysis zaidat et al stroke 200222
IV plus IA ThrombolysisZaidat et al Stroke 2002
  • No difference between groups for:
    • Recanalisation (70%)
    • Outcome: mRS 0-2 77% in survivors
    • Sympt hemorrhage (15-20%)
    • Mortality: 50% !!
i a t post operative period
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%
vertebrobasilar thrombosis
Vertebrobasilar Thrombosis
  • Life-threatening event: mortality 75-86%
  • No effective therapy
  • Heparin: accepted but unproven
  • Some authors reporting success with IAT:
    • Retrospective
    • Small groups
vertebrobasilar i a t
Vertebrobasilar I.A.T.
  • Time frame: 1 to 48 h after last progression
  • Most patients present 24-48 h after onset
  • Only 3 studies with > 10 patients
vertebrobasilar i a t27
Vertebrobasilar I.A.T.
  • Cohort mortality is decreased compared to historic controls when successful thrombolysis has been achieved.
  • Benefit even 24 h after presentation.
vertebrobasilar i a t 4 major series
Vertebrobasilar I.A.T.4 major series
  • Average time to therapy: up to 24h
  • Mortality: 46%, 54%, 67%, 75%
  • Recanalization: 75%, 71%, 54%, 75%
  • Hemorrhage: 7%, 0%, 9%, 15%
  • Rethrombosis: --- 10%, --- 30%
  • Recanalized mortality: 26% to 30%
vertebrobasilar i a t factors affecting outcome
Vertebrobasilar I.A.T.Factors affecting outcome
  • Infarction of a critical amount of brainstem tissue
  • Coma and quadriparesis at presentation
  • Lack of recanalization, rethrombosis
i a t anterior circulation
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)
i a t anterior circulation32
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.
i a t vertebrobasilar system
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
i a t vertebrobasilar system34
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.
indications in anterior circulation
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)
indications in posterior circulation
Indications in Posterior Circulation
  • Worsening symptomatology despite heparin
  • Visualized occlusion
  • Up to 24h after onset of worsening
  • UK 250,000-500,000 per H x 2 then 250,000u per H x 4. With heparin.
  • tPA: less well studied.