Endovascular Intervention In Acute Stroke And Occlusive Vascular Disease

Robert P. Booth, M.D.
Robert P. Booth, M.D. is Associate Professor of Radiology at University of Florida Health Science Center / Jacksonville.

Introduction

Cerebrovascular disease, particularly ischemic stroke, remains among the leading causes of serious long term disability and is the third leading cause of death behind heart disease and cancer.1,2 Cerebral ischemia is the significant reduction of blood flow to all or part of the brain. The clinical effects of a cerebral ischemic event depend upon the duration and degree of flow impairment and the volume and location of brain tissue affected. Restoration of adequate perfusion to prevent or limit the progression of cerebral ischemia to irreversible infarction is the goal of early intervention in acute stroke management.

Studies have shown that the majority of ischemic strokes are due to acute thrombo-occlusion of cerebral vessels.3 Primary intravascular treatment to dissolve the occluding thrombus within the cerebral vessel is a therapy that has evolved over the past thirty years. Intravenous administration of thrombolytics has shown promise in the acute treatment of stroke in up to thirty percent of patients.4 Based on the foundations of coronary and peripheral vascular thrombolysis, techniques that have proven effective, it is reasonable to consider that increasing the concentration of the thrombolytic agent at the site of the thrombus may enhance the effectiveness of the thrombolytic agent increasing the speed of clot lysis which may be critical to clinical outcome. This can be accomplished using microcatheters angiographically directed to the site of the occluding thrombus. The thrombus is then dissolved by directly administering a thrombolytic agent into the clot, a technique referred to as local intra-arterial thrombolysis (LIAT).5

Local Intra-Arterial Thrombolysis

The evaluation of a patient considered for intra-arterial thrombolysis begins with a cranial CT to exclude an intra-cranial hemorrhage, a contraindication to thrombolysis. Once the CT has been reviewed, discussion between the stroke neurologist and endovascular neuroradiologist will determine if the patient is a candidate for intra-arterial thrombolysis.

The technique of LIAT in the treatment of acute stroke must be initiated as rapidly as possible. The precise therapeutic window for LIAT has not been defined, but initiation within six hours of symptom onset for anterior circulation strokes is reasonable. Basilar artery events may allow a wider window. The procedure is usually performed from a femoral approach and is preceded by diagnostic angiography to establish the diagnosis and location of the occluding thrombus. Recent technological advances in microcatheters allow the navigation of small catheters through the tortuous cerebral arteries and directly into the blood clot that is causing the stroke. Several thrombolytic agents have been developed, but the two most
commonly used agents currently are urokinase and tissue plasminogen activator. The effect of the thrombolytic agent can be augmented by direct mechanical disruption of the clot with the microcatheter and guidewire. Urokinase is currently the most commonly used intra-arterial thrombolytic agent. It is highly effective in dissolving clots and may be administered in doses exceeding one million units.

While an acute occlusion in any accessible cerebral vessel is potentialy treatable, the best results appear to have been obtained with occlusions of the proximal middle cerebral and distal basilar arteries (see Figure 1). Recanalization of acute basilar occlusion by LIAT appears to reduce mortality associated with this arterial lesion.6 PROACT (Prolyse In Acute Cerebral Thromboembolism) is a prospective randomized, double-blind, multi-center trial comparing LIAT with placebo. Patients with symptomatic middle cerebral artery occlusions of less than six hours duration are being evaluated in this trial. Phase II data from this trial suggests that LIAT conducted with Pro-urokinase is associated with superior recanalization in acute stroke compared with placebo.7 Presently, no direct comparison between direct arterial thrombolysis and peripherally administered intravenous thrombolysis has been conducted.

Figure 1. A 43-year-old presented with acute onset right-sided neglect and left facial droop. Angiography revealed a proximal left middle cerebral artery occlusion (Figure 1A, left). Complete revascularization was restored following intra-arterial urokinase with a total of 750,000 units of urokinase given (Figure 1B, center, arrow points to microcatheter, and 1C, right).

Presently, the major complication of LIAT is intracranial hemorrhage, which can occur in 7-40% of cases depending on the level of occlusion. This appears to be related to reperfusion of infarcted tissue and is directly related to the duration of the occlusion and the amount of brain tissue involved. Because of the risk of hemorrhage with thrombolytics, patients with recent surgery, active internal bleeding, or CT documentation of a large recent infarct or intra-cranial hemorrhage are not candidates for intra-arterial thrombolysis.

Intracranial Balloon Angioplasty

Not infrequently, the site of thrombo-embolic occlusion occurs at or originates from a vessel compromised by atherosclerotic occlusive disease. Artherosclerotic lesions in the distal carotid or proximal middle cerebral artery are not accessible to endarterectomy since both lesions are located intracranially. Medical therapy offers help for these patients, but occasionally other pre-existing medical conditions prevent effective medical treatment. Patients with endovascularly accessible stenoses can now be treated with intra-arterial balloon dilatation, a technique which can be applied to the proximal cerebral vessels and distal carotid artery.8-10 The development of microcatheter balloons with an extremely low profile and high flexibility allows endovascular treatment of previously inaccessible lesions. Similar to techniques used in peripheral angioplasty, a small balloon is passed through a guiding catheter and positioned at the stenosis. The balloon is inflated and the artery is dilated to re-establish effective flow (Figure 2). Two potential complications that may occur with balloon angioplasty are arterial dissection and distal emboli. Distal thrombo-emboli may be treated with LIAT as in acute stroke.11 Arterial dissections frequently respond to repeat balloon angioplasty. Although re-stenosis occurs, experience suggests that this occurs less frequently than at the carotid bifurcation. As intra-arterial stents become smaller and more pliable, arterial stenting may offer another treatment option for recurrent stenoses and problem arterial dissections. As technological advances continue, direct endovascular treatment of intracranial stenoses may become the treatment of choice in place of extended medical therapy.

Figure 2. A 53-year-old with multiple medical problems suffered several ischemic events with transient symptoms involving the left middle cerebral artery distribution. Angiography revealed a left internal carotid artery stenosis. Balloon angioplasty was performed with acceptable results (Figure 2A, left, and 2B, right). The patient has remained asymptomatic since the procedure.

Stenoses involving the carotid bifurcation have traditionally been effectively treated with surgical carotid endarterectomy. Recent advances in endovascular stenting now allow this technique to be applied to stenoses of the cervical internal carotid artery including the carotid bifurcation. For this procedure to be acceptable as a routine alternative to traditional surgery, it will have to be shown to have a low complication rate and reasonable long-term efficacy similar to carotid endarterectomy. Currently, carotid stenting offers a realistic alternative to patients who, for medical reasons, are not surgical candidates. Studies comparing carotid stenting with surgical endarterectomy will soon be underway.

Summary

In summary, advances in microcatheters and low profile balloons have made possible direct intravascular treatment of acute thrombo-occlusion and atherosclerotic stenoses in selected patients. The precise risk-benefit ratio of LIAT and intracranial angioplasty is not known, but direct endovascular therapy will continue to evolve as more experience and data become available. Close clinical cooperation between the stroke neurologist and endovascular neuroradiologist is necessary to maximize patient selection, treatment options and definitive care.

REFERENCES

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  10. Kachel R, Basches S, Heerklotz I, et al. Percutaneous transluminal angioplasty of supra-aortic arteries, especially the internal carotid artery. Neuroradiology. 1991; 33(3); 191-194.
  11. Cronquist M, Pierot L, Boulin A, et al. Local intra-arterial fibrinolysis of thromboemboli occurring during endovascular treatment of intracerebral aneurysms: a comparison of anatomic results and clinical outcome. AJNR. 1998; 19: 157-165.
Jacksonville Medicine / November, 1998

 

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