Intraarterial thrombolytic treatment

Masoud Mehrpour M.D.

Time is brain

Cor e THE PENUMBRA CONCEPT

Ischemic penumbra

The concept of penumbra during focal cerebral ischemia refers to the regions of brain tissue, usually peripheral in location, where blood flow is sufficiently reduced to result in hypoxia severe enough to arrest physiological function, but not so complete as to cause irreversible failure of energy metabolism and cellular necrosis

Ginsberg MD. Adventures in the pathophysiology of brain ischeia: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis lecture. Stroke. 2003; 34: 214 –223

Interventional Treatments for Ischemic Stroke

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IV r-tPA

is the first line of treatment for ischemic stroke, efficacious and cost-effective for patients with acute ischemic stroke treated up to 4.5h of symptom onset and is relatively ineffective for proximal occlusions •

Intra-arterial thrombolysis

is more effective for proximal occlusions and can be used up to 6 hours after stroke onset and later in some cases •

Thrombectomy

is beneficial for about 50% of patients with proximal occlusions

Endovascular Intervention

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Intra-arterial Thrombolytic

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Mechanical Embolectomy

Why consider IAT

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IV rt-PA:

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Limited to < 3H

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Clear but limited clinical benefit

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Rate of recanalisation (doppler):

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Complete: 32% Partial or none 68%: 67% MCA, 25% BA, no ICA (Christou et al 2001)

Why consider IAT

• • • •

Persistent obstruction



deficit Increase the therapeutic window Post-operative stroke persistent Reduce hemorrhagic complications

I.A.T. Theoretical Advantages

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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

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Catheter manipulation Systemic heparinisation Delay in initiation of thrombolysis Skilled facilities Non cooperative patients

VII. Intra-arterial tPA

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< 6 hours for selected patients who are NOT eligible for IV tPA.

Must be at an experienced stroke center with immediate access to angio and interventionalists

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IA tPA is reasonable for pts who have contraindications to IV tPA (recent surgery, age, time frame) Availability of IA tPA should NOT preclude IV tPA in eligible patients

Intra-arterial TPA in stroke

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Option for treatment of selected patients who have major stroke of up to 6 hours duration and with large artery occlusions such as ICA/basilar/MCA and otherwise candidates for IV rtPA (Class I, Level B)

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Reasonable in patients who have contraindications to use of IV tPA , such as recent surgery (Class IIa, Level C)

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Should generally not preclude IV tPA in otherwise eligible patients (Class III, Level C)

XII. Endovascular Intervention

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Mechanical removal of clot

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Clinical trials have shown that thrombectomy with mechanical thrombolysis devices is indeed feasible in the treatment of acute stroke.

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Many devices have been discontinued

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MERCI Retriever has received FDA clearance.

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Catch Retriever system

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Penumbra system

Intra-arterial therapy in acute Stroke

Penumbra suction device

Merci clot retrieval

EMERGING THERAPIES Endovascular therapies Mechanical Thrombectomy 2005 The MERCI Trials : 48 % Recanalization Concentric Retriever device

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Smith et al. The MERCI TRIAL Stroke. 2005 Jul; 36(7):1432-8.

Mechanical thrombectomy

Penumbra system

Indications in Anterior Circulation

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Persistent occlusion post IV tPA < 3h Within 6 h, but time to treatment is correlated with outcome.

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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)

Case Study #3 Acute R ICA occlusion Stroke

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50 y.o. female Acute onset Left hemiparesis and slurred speech Hx=HTN Ct done 40 mins after onset NIHSS=14 + IV Tpa in 60 min

CT CTA L M1 occlusion

Interventional Treatments for Ischemic Stroke Occlusion L ICA Male 79 IA NIHSS = 19 tPA 5h after onset After thrombectomy complete L ICA recanalization NIHSS = 5

(Demaerschalk and Yip, 2005; The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group, 1995

Vertebrobasilar I.A.T.

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Time frame: 1 to 48 h after last progression

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Most patients present 24 - 48 h after onset

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Only 3 studies with > 10 patients

Indications in Posterior Circulation

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Worsening symptomatology despite heparin

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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.

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tPA: 10 mg.

Vertebrobasilar I.A.T.

Factors affecting outcome

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Infarction of a critical amount of brainstem tissue

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Coma and quadriparesis at presentation

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Lack of recanalization, rethrombosis