Current Treatment of Ischemic Stroke in the University at Buffalo

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Contents

Authors

Rodney M. Samuelson MD,1 Siddiqui, Adnan MD, Elad I. Levy MD,3 and

L. Nelson Hopkins MD4

Affiliations

Millard Fillmore Gates Hospital, Kaleida Health;1-4 Department of Neurosurgery and Toshiba Stroke Research Center1-4 and Department of Radiology,3,4 School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York

Introduction

Stroke is the third-leading cause of death. It affects 750,000 people in the US each year1. Ischemic stroke is often due to either embolization of intravascular debris to cerebral vessels or hemodynamic and thrombotic consequences of intracranial vascular stenosis. The central region or the ischemic core of the occluded vascular territory rapidly infarcts. The surrounding ischemic area, known as the penumbra receives enough collateral supply such that it may be saved if adequate cerebral perfusion is reestablished in a timely fashion. The concept of restoring normal perfusion to the penumbra, thereby restoring neural tissue and hence neurological function, is fundamental to the various strategies for acute stroke therapy. The following review discusses medical management, endovascular treatment, and future research for each of these broad areas of ischemic stroke.In the multicenter PROACT II3 trial, patients presenting with signs of an MCA stroke underwent angiography within 6 hours of symptom onset. If angiography confirmed an occlusive lesion of the proximal MCA, the patient was randomized to receive 9 mg of intra-arterial pro-urokinase over 2 hours or to receive an intravenous heparin infusion. The recanalization rate with this protocol was 66% in the treatment group, compared with 18% in the placebo group. The primary endpoint of the trial, an mRS score of less than 2 at 90 days, was achieved in 40% of patients receiving intra-arterial thrombolysis versus 25% of those untreated.

One of the main objectives of clinical stroke research has been to prolong the brief therapeutic time window allowed by intravenous and intra-arterial thrombolysis. Mechanical recanalization has been suggested as a method to reduce the incidence of intracerebral hemorrhage because little or no thrombolytic agent is used. Mechanical thrombolysis has also been reported to result in a higher and faster rate of recanalization, compared with intra-arterial administration of tPA. The MERCI device was tested in a randomized clinical trial. Using this clot retriever, recanalization was achieved in 69 of 151 (46%) patients in an intention-to-treat analysis and in 68 of 141 (48%) patients in whom the device was deployed.5 This rate is significantly higher (18%) than that expected by comparison with a historical control (P<0.0001)

PATIENT SELECTION

In the University at Buffalo Department of Neurosurgery, interventional treatment of acute stroke has evolved over the last thirteen years. From 1994 to 1996, intra-arterial (IA) injection of urokinase or prourokinase was used. In 1997, IA tissue plasminogen activator (tPA) and mechanical clot lysis (angioplasty, clot perturbation with a microwire, snare retrieval) were added to this regimen. Reteplase (1-4 units) became the IA lytic in 1999. Since 2001, a combination of mechanical and thrombolytic treatments have been used. Each case is guided by patient-specific factors and intraprocedural findings. Currently methods include pharmaceuticals (low-dose heparin, reteplase, and IIb-IIIa inhibitors), plus mechanical clot retrieval with progressive generations of the Merci device (Concentric Medical, Mountain View CA), and a Wingspan (Boston Scientific Target, Fremont, CA) stent for unsuccessful Merci clot retrieval. Patients are triaged upon arrival at the hospital. Time from onset and findings on CT perfusion imaging are used to guide treatment. Patients presenting ≤ 3 hours from symptom onset are treated with intravenous (IV) tPA if their National Institutes of Health Stroke Scale (NIHSS) score is less than or equal to 8, and with combination IA therapies if their NIHSS score is greater than 8. Those treated between 3 to 6 hours from symptom onset receive IA thrombolytics or combination mechanical therapies. After 6 hours, patients with ischemic strokes of the anterior circulation may still benefit from revascularization, provided their core infarction (“black hole”) is not located primarily within the basal ganglia and is not greater than 33% of the entire region at risk.2 If the core infarction is more than 33%, the risk for neurologic worsening from intracranial hemorrhage is unacceptably high. Other patient-specific factors (i.e. age, medical comorbidities, type and severity of neurologic deficit) are important for decision making as well. In patients with posterior fossa infarctions, interventional therapies are considered for as long as 12 to 24 hours. In these cases, magnetic resonance imaging with diffusion-weighted and apparent-diffusion coefficient sequences are used to further guide patient selection.


Although only tPA and Merci mechanical clot retrieval are currently FDA-approved treatments for acute stroke, self-expanding stents have recently been used as adjunctive treatment. We have been approved to treat 20 patients with ischemic stroke with an approved self-expanding stent. Future directions for revascularization include new pharmacologic agents, better clot disruption techniques or devices, and more refined methods for complication avoidance.

Technique

Standard femoral access is obtained and a 6-French guide catheter (or larger) placed in the target vessel proximal to the occlusion. A diagnostic catheter is first used to obtain initial angiographic images to confirm an occlusion in the target vessel. Provided that the patient has favorable aortic arch anatomy, the 7-french balloon tipped guide catheter from Concentric medical is used (Concentric Medical, Mountain View CA). Heparin is then administered to achieve a target ACT of 220 to 250 seconds. Microcatheterization of the occluded vessel is then performed, and microangiography distal to the occlusion demonstrates the severity of the clot burden. At this point, individual therapies are selected. In the majority of cases, the MERCI device is used one time before any IA lytic. Failing this, IA lytic is given prior to the second MERCI attempt. If the MERCI device fails to provide adequate revascularization after 2-4 attempts, an intracranial stent is placed. The IV integrillin weight based loading dose is given immediately after the stent is placed in patients not currently on ASA/Plavix, or for whom IA integrillin was not used as an adjunctive therapy. Although the quadruple combination of IA lytic, IA integrillin, MERCI, and an intracranial stent has been successfully used in our institution, it is associated with an unacceptably high risk of symptomatic intracranial hemorrhage and death. Therefore, discretion must be used when adding each of these techniques to a combination therapy. The majority of our patients do not receive all four therapeutic techniques. This includes the majority of our patients with unsuccessful revascularization. Balloon angioplasty is occasionally needed when there is residual clot within the stent lumen or when an intracranial stenosis is identified. Other techniques, such as microwire morcelization and the Fogarty maneuver are used occasionally on recalcitrant lesions, although the success rate under such circumstances is low.

Follow up

All patients are observed for at least 24 hours in an intensive care setting. Moderate or severe hypertension (systolic blood pressure >150 mm Hg, diastolic blood pressure >95 mm Hg) is treated with IV antihypertensive therapy to lower the risk of reperfusion injury following stenting.4 Aspirin (enteric-coated aspirin, if necessary) (325 mg per day) and clopidogrel (75 mg per day) or ticlopidine (250 mg twice daily) is continued (aspirin for 6 months; clopidogrel or ticlopidine for 3 months).CT imaging is obtained at post-procedure, at 24 hours, and whenever clinically indicated.</nowiki> Upon discharge, neurological evaluation and analysis of stroke scale scores are obtained. Follow up evaluations in clinic are performed at 30 days, 3 months, and 6 months. This included mRS, NIHSS, and Barthel Index scores. The majority of patients undergo a single-vessel angiogram of the treated artery at 3 months post-procedure. If the patient is experiencing neurological deficits related to the previously treated vascular territory and the percentage of in-stent stenosis is >50%, balloon angioplasty of the in-stent stenosis is performed

References:

1. American Heart Association: Heart disease and stroke statistics -- 2005 update. Dallas, Texas.2. Koenig M, Kraus M, Theek C, Klotz E, Gehlen W, Heuser L: Quantitative assessment of the ischemic brain by means of perfusion-related parameters derived from perfusion CT. Stroke 32:431-437, 20013. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F: Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 282:2003-2011, 1999.4. Meyer JS, Gilroy J, Barnhart MI, Johnson JF: Therapeutic thrombolysis in cerebral thromboembolism. Double-blind evaluation of intravenous plasmin therapy in carotid and middle cerebral arterial occlusion. Neurology 13:927-937, 1963.

5. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, Lutsep HL, Nesbit GM, Grobelny T, Rymer MM, Silverman IE, Higashida RT, Budzik RF, Marks MP: Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke 36:1432-1438, 2005.

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