ENDOVASCULAR THERAPIES FOR ACUTE STROKE

Cerebral Arteriogram

Cerebral Anatomy

Brain Imaging

Acute Ischemic Stroke (AIS) Therapy Main goal is to restore blood flow and improve perfusion to the affected brain region. Cornerstone of treatment is rapid recanalization of the parent vessel by dissolving the clot or mechanical extraction of the clot.

Acute Ischemic Stroke Therapy 1996, the Federal Drug Administration (FDA) approved intravenous (IV) rt-pa for patients with AIS based on the results of the NINDS rt-pa Stroke Study. Current guidelines, initiate IV rt-pa for patients within 3 to 4.5 hours of symptom onset.

Thrombolytic Eligibility Inclusion Criteria for 0 4.5 Hours History Exact time of stroke onset No head trauma, stroke or MI within 3 months No gastrointestinal- or urinary tract bleeding within 21 days No major surgery within 14 days No arterial puncture at a noncompressible site within 7 days No history of intracranial hemorrhage Examination Measurable neurological impairment without spontaneous improvement No active bleeding or evidence of acute trauma No seizure at stroke onset No evidence of postictal condition No symptoms of subarachnoid bleed present

Thrombolytic Eligibility Inclusion Criteria for 0 4.5 hours Labs/vitals INR <1.7 Heparin use in previous 48 h, aptt in normal range Platelet count >100 000/ml Serum glucose > 50 mg/dl Systolic blood pressure <185 mmhg; Diastolic blood pressure <110 mmhg Head CT/imaging No intracranial hemorrhage No hypodensity/ischemia involving <1/3 cerebral hemisphere ADDITIONAL EXCLUSION CRITERIA FOR 3.0 4.5 HOURS Age older than 80 years Oral anticoagulation therapy, irrespective of INR Baseline NIHSS >25 History of diabetes and stroke

Intra-Arterial (IA) Thrombolysis Potential advantage of IA administration of thrombolytic agents is high-concentration local drug delivery into the clot with reduced systemic effects. Majority of data on IA thrombolytics originates from studies with recombinant pro-urokinase. The Prolyse for Acute Cerebral Thromboembolism I trial (PROACT-I) and PROACT-II. Patients treated within 6 hours of symptom onset.

Intra-Arterial Indications Symptom onset between 3 to 6 hours NIHSS > 8 or isolated aphasia Some patients not IV rt-pa candidates No improvement after 30 minutes of IV rt-pa and large to medium vessel occlusion Vertebrobasilar occlusion extended to 24 hours

Intra-Arterial Thrombolysis

Mechanical Embolectomy Mechanical thromboembolectomy techniques are typically utilized in patients with contraindications to thrombolytic therapy or failed recanalization after thrombolysis. Currently there are only two FDAapproved devices for catheter-based mechanical embolectomy up to 8 hours. MERCI device Penumbra device

MERCI The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) system is an embolectomy device (Concentric Medical, Inc., Mountain View, California, USA) approved by the FDA as a Humanitarian Device Exemption (HDE) in 2004.

MERCI The device has a flexible tapered wire with helical loops that can be embedded in the thrombus for retrieval

Example of Clot Removed by MERCI

Penumbra The Penumbra system (Penumbra, Inc., Alameda, California, USA) is another device approved by the FDA as a HDE in 2008. It was designed to mechanically disrupt thrombus and aspirate clot fragments through a catheter

Penumbra Device

Penumbra Device Clot Extraction

Complications IA pharmacological thrombolysis is associated with reduced and slower rates of recanalization as well as potential for higher risk of intracerebral hemorrhage.

Disadvantage Monotherapy Likewise, FDA-approved mechanical thromboembolectomy techniques have suboptimal rates of recanalization when used alone. In retrospective multicenter study, the Penumbra device achieved recanalization rate of 83%. IA adjunctive thrombolytic therapy was used in 68.6% of patients. The MERCI Retriever System achieved recanalization rate of 55% and 68% after adjunctive thrombolytic therapy.

Approaches to Recanalization Medical thrombolysis Endovascular thrombectomy (clot retrieval or suction aspiration devices) Augmented fibrinolysis (catheter-tipped ultrasound and externally applied ultrasonography) Mechanical clot disruption (ie, emergent angioplasty and stenting)

Adjunctive Therapies Currently, strategies aimed at improving and expediting the rates of recanalization are utilizing a combination of these therapies. IMS Trial combines IV and IA thrombolytic therapy. Enables the relative speed and widespread availability of IV thrombolysis to initiate recanalization while assuming the inherent delays of the more effective IA thrombolysis.

Mechanical Disruption Mechanical disruption methods such as balloon angioplasty and stenting may improve recanalization rates by increasing the surface area for thrombolysis. In one case series, partial to complete recanalization rates were achieved in 91.2% of patients treated with angioplasty. The rate of symptomatic intracerebral hemorrhage was 2.9%. Potential complication of angioplasty include arterial dissection or rupture, distal embolism and occlusion of associated perforating vessels.

Mechanical Disruption Limited data are available about the use of angioplasty and stenting in AIS. Small case series have shown trends for aggressive mechanical clot disruption as adjunct to thrombolytic therapy to achieve earlier and better rates of recanalization with potential for low rates of periprocedural complications.

Wingspan Stent System Angioplasty Slow inflation Submaximal Stent Placement Self expandable Continued lumen gain

Intervention 2.5 x 13mm Cypher Stent 4/7/05