Endovascular Treatment of Stroke

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Chapter 85 Endovascular Treatment of Stroke

Kyle M. Fargen, Gregory J. Velat, Michael F. Waters, Brian L. Hoh, J. Mocco

Stroke is the third leading cause of death in the United States, accounting for more than 143,000 deaths each year. The Centers for Disease Control and Prevention estimates approximately 795,000 strokes occur annually in the United States. Of these, 610,000 are sentinel events, with the remainder occurring in those who have suffered a prior stroke.¹ Stroke is a leading cause of long-term disability due to loss of independence, language, motor skills, and cognitive abilities.¹ The American Heart Association has estimated the financial burden of stroke to be nearly $70 billion in 2009 due to both direct and indirect costs.² Although acute stroke is dichotomized into both ischemic and hemorrhagic etiologies, the vast majority of strokes are secondary to ischemia. Roughly 80% to 85% of acute strokes are secondary to thromboembolic vessel occlusion, typically arising from cardiac, carotid, or intracranial artery pathology.³

Timely arterial recanalization and prevention of reocclusion after treatment have become integral foci of the modern management of acute stroke. Current therapeutic modalities include intravenous chemical thrombolysis, intra-arterial mechanical and chemical thrombolysis, and stenting. Rapid diagnosis and treatment of acute stroke have been shown to improve patient outcomes in multiple studies.⁴^–¹⁰ However, multiple barriers exist that may prevent patients from receiving timely revascularization, including delay in diagnosis, resource constraints, and lack of physicians trained in stroke management. Regionalization of stroke care has been popularized in recent years in the United States to combat such barriers. Despite these efforts, it is estimated that less than 1% of patients suffering an acute stroke receive intravenous thrombolytic therapy.¹¹ The recent results of the third European Cooperative Acute Stroke Study (ECASS), which showed benefit in patients who received intravenous recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset,¹² may increase the number of patients eligible to receive intravenous thrombolytic therapy.

The only medical therapy approved by the U.S. Food and Drug Administration (FDA) for acute stroke remains intravenous rtPA. Recently, the Merci Retriever thrombectomy device (Concentric Medical, Mountain View, CA) and the Penumbra System thromboaspiration device (Alameda, CA) also gained FDA approval for the treatment of acute stroke.

Intravenous thrombolysis, intra-arterial chemical and mechanical thrombolytic therapies, and stenting for acute ischemic stroke are discussed in this chapter. Specific indications, methods, potential complications, and supportive evidence are presented for each of the modalities.

Occlusion and Recanalization

Integral to the endovascular treatment of acute ischemic stroke are the principles of arterial occlusion, recanalization, and reocclusion. Stroke onset typically correlates with acute occlusion of an intracranial artery by platelet- and/or fibrin-rich clot, resulting in reduced parenchymal perfusion. If perfusion is not restored in a timely fashion, a hypoxia-induced cellular cascade is triggered, resulting in cell vulnerability and potential cellular necrosis. Various factors may influence the extent of cellular necrosis, including potential collateral blood flow contingent upon the patency of the circle of Willis or anastomoses from external carotid or posterior circulation vessels, patient coagulation status, and platelet function, as well as other patient comorbidities. Irreversible neuronal death may occur within 3 to 4 minutes of ischemia. Potentially salvageable tissue on the verge of necrosis is referred to as the penumbra. The primary goal of endovascular stroke therapy is to restore blood flow to the brain tissue within the penumbra and territory at potential risk while avoiding hemorrhagic transformation of unsalvageable tissue.

Arterial recanalization is widely accepted as a surrogate marker of efficacy for stroke therapies. The Thrombolysis in Myocardial Infarction (TIMI) scale is accepted among neurointerventionalists as a semiquantitative measure of vessel recanalization (Table 85-1).¹³ Transcranial Doppler ultrasonography has also shown promise in evaluating vessel recanalization.¹⁴^–¹⁶ Successful recanalization has been linked to improved clinical outcomes in many series.¹⁷ Pretreatment residual flow has been shown to be predictive of both time to achieve recanalization and likelihood of a successful intervention.¹⁵ In a meta-analysis of recanalization and outcome, Rha and Saver demonstrated a strong correlation between arterial recanalization and improved functional outcomes with reduced mortality.¹⁷ Successful arterial recanalization at the time of intervention does not always correlate with lasting benefit, because some vessels may reocclude. Reocclusion rates as high as 34% have been reported in some studies following intra-arterial administration of rtPA.¹⁸^–²⁰ In addition, distal propagation of thrombus has been reported in approximately 16% of patients undergoing pharmacologic or mechanical thrombolysis.²⁰ Potential reperfusion injury may occur when the blood–brain barrier becomes destabilized. Secondary cerebral edema and/or intracranial hemorrhage may result, possibly necessitating operative intervention.

TABLE 85-1 TIMI Flow Grading System ¹³

TIMI Grade	Classification	Criteria
0	No perfusion	No recanalization of the primary occlusive lesion
1	Penetration without perfusion	Incomplete or partial recanalization with flow past the initial occlusion, but no distal branch filling
2	Partial perfusion	Partial recanalization with incomplete or slow distal branch filling
3	Complete perfusion	Full recanalization with filling of all distal branches

Goals of Therapy

The goals of endovascular treatment of stroke are: (1) obtain timely recanalization of the occluded vessel (TIMI grade 2 or 3 blood flow), (2) prevent reocclusion following recanalization, (3) minimize distal propagation of thrombus, and (4) avoid intractable cerebral edema and intracranial hemorrhage following reperfusion.

Presentation

Patients suffering an acute ischemic stroke most commonly present with sudden-onset neurologic deficit(s) that localize to the brain territory supplied by the affected vessel(s). It is imperative to perform a thorough but succinct history and neurologic examination to assess the extent of stroke. Physicians must gather information regarding the progression of neurologic deficit over time and any improvements that have occurred since onset, as spontaneous improvement may indicate a transient ischemic attack or point to an alternative diagnosis, such as seizure. The National Institute of Health Stroke Scale (NIHSS) quantitatively rates the severity of the stroke and has demonstrated excellent reliability and clinical utility.²¹^–²³ The scale ranges from 0 (no symptoms) to 42 and grades patient deficits in multiple functions, including motor, sensory, language, and alertness. Generally, scores of 1 to 5 represent mild stroke, 5 to 20 moderate to severe stroke, and greater than 20 very severe stroke. The NIHSS and its booklet are accessible online at the National Institute of Neurological Disorders and Stroke (NINDS) Web site (http://www.ninds.nih.gov/).

Imaging

All patients presenting with stroke symptoms should undergo brain imaging. Computed tomography (CT) is the most readily available and efficient imaging modality, although magnetic resonance imaging (MRI) may also be performed. Early noncontrasted CT scanning is critical for evaluation of intracranial hemorrhage and serves as the primary differentiator for standard of care therapies. In addition, noncontrasted CT scanning of the head may reveal hypodensities consistent with evolving territories of infarction, cerebral edema or herniation, loss of gray–white matter differentiation, or arterial occlusion referred to as the “hyperdense sign.” At the University of Florida, computed tomography angiography (CTA) of the head and neck and cerebral CT perfusion are performed on all patients who present with acute stroke symptoms. It is imperative the aortic arch and major arteries of the head and neck be visualized to evaluate for arterial occlusion, flow-limiting stenosis, dissection, or other vessel anomalies. CT perfusion is used to assess the extent of stroke and the amount of potentially salvageable brain parenchyma. Tissue with preserved cerebral blood volume, despite reduced cerebral blood flow and increased mean transit time, represents the stroke penumbra (Fig. 85-1).^24,²⁵ CT perfusion may be limited at visualizing the posterior fossa due to significant bone artifact and beam scatter; however, it is hoped that newer imaging technologies and techniques will ameliorate this difficulty. Alternatively, some institutions rely on diffusion-weighted MRI to evaluate the brain’s physiologic state. Whichever modality is used, timely evaluation of actual brain physiology is rapidly becoming a new standard in the cutting-edge treatment of stroke.

FIGURE 85-1 CTA of a patient presenting with symptoms of right MCA ischemia. A, CTA demonstrates right M1 segment occlusion from thrombus. B, Perfusion imaging reveals an elevated mean transit time in the right MCA distribution. C, Perfusion imaging demonstrates decreased cerebral blood flow within the right MCA distribution. If perfusion imaging demonstrates spared cerebral blood volume, these findings indicate a potential therapeutic target for intervention.

Patient Selection

Indications and contraindications for intravenous thrombolysis are listed in Table 85-2. Intracranial hemorrhage is a direct contraindication for revascularization therapy. The therapeutic window for intravenous rtPA has been extended to 4.5 hours from the onset of symptoms based on results of the recent ECASS III trial.^12,²⁶ Patients eligible for intravenous rtPA should undergo this treatment prior to attempts at endovascular therapy. If patients fail to improve neurologically with intravenous rtPA, present outside of the therapeutic window, or have a contraindication to intravenous rtPA, endovascular therapy may be considered, including the use of intra-arterial rtPA, mechanical disruption using the microwire, the use of mechanical thrombectomy/aspiration devices, angioplasty, stenting, or a combination of procedures in those with persistent occlusive thrombi.

TABLE 85-2 Indications and Contraindications to rtPA Administration

Indications	Contraindications
• Ischemic stroke onset within 4.5 hours of drug administration • Measurable deficit on NIHSS examination • No hemorrhage or nonstroke cause of deficit on CT • Age >18 years

Administration 0.9 mg/kg infused intravenously over 60 minutes, with 10% of the initial dose given as a bolus over 1 minute

The relative amount of ischemic parenchyma should be considered strongly when deciding to pursue endovascular treatment. Specifically, unsalvageable tissue (defined by regions with decreased cerebral blood volume in the setting of increased mean transit time and decreased cerebral blood flow on perfusion imaging) comprising greater than one third of the overall brain territory at risk of ischemia is a relative contraindication to endovascular therapy. In our experience, these patients are at high risk of hemorrhagic transformation following intra-arterial pharmacologic and/or mechanical thrombolysis or stenting, particularly if the nonsalvageable region involves the basal ganglia. Other factors linked to poor clinical outcomes in patients undergoing endovascular therapy include advanced age (greater than 75 years), presentation NIHSS score greater than 18, and admission glucose greater than 150 mg/dl.⁹ While the conventional ideal therapeutic window for endovascular therapy is within 6 to 8 hours of symptom onset,^10,^26,²⁷ patients are increasingly being successfully treated outside of this time frame guided by physiologic imaging (CT perfusion or MRI perfusion).^28,²⁹

Intracerebral Hemorrhage

The major complication of endovascular therapies for stroke is intracranial hemorrhage, which is estimated to occur in roughly 5% to 10% of patients undergoing intravenous tissue plasminogen activator therapy.^7,^30,³¹ Clinically significant intracerebral hematomas, so-called symptomatic intracerebral hemorrhage (SICH), develops in around 3% of patients. The frequency of SICH increases with the concomitant presence of early signs of infarction on CT scan prior to administration.^31,³² Furthermore, symptom severity, diabetes mellitus, and elevated blood glucose are well-demonstrated independent risk factors for SICH.^32,³³ Other possible risk factors include high systolic blood pressure, low platelets, advanced age, and delay in treatment. Intra-arterial tissue plasminogen activator, in contrast to venous, has a slightly higher risk of SICH. Estimates of SICH in those receiving intra-arterial thrombolysis are approximately 6% to 12%, while those receiving both intravenous and intra-arterial administration are estimated to be roughly 9% to 20%.^10,³¹

The pathophysiology of post-treatment SICH appears to be primarily the result of reperfusion injury with hemorrhagic transformation at ischemic sites.³⁴ Ischemia results in disruption of the blood–brain barrier, causing leakage from vessels, tissue edema, and loss of autoregulation secondary to increased free radical and matrix metalloproteinase activity.^35,³⁶ Reperfusion of damaged vessels results in small ruptures with microhemorrhages that may ultimately enlarge into a hematoma due to disruption of the normal clotting cascade by the presence of thrombolytic agents.

Intravenous Thrombolytic Therapy

Intravenous thrombolytic therapy with rtPA was the first FDA-approved intervention for acute stroke. The NINDS trial, published in 1995, was a large, randomized, placebo-controlled study consisting of more than 600 patients randomized to rtPA versus placebo within 3 hours of stroke onset.⁴ At 24 hours, no difference was seen in NIHSS improvement between those receiving rtPA and those receiving placebo. At 3 months, patients receiving rtPA had 1.7 times greater odds of a favorable outcome than did those receiving placebo. SICH occurred in 34 of the 312 patients receiving rtPA (20 were symptomatic, of which 9 were fatalities), compared to 11 of the 312 patients receiving placebo (2 symptomatic, 1 fatality). Two additional trials, ECASS I and II, demonstrated comparable results with improved functional outcomes but increased risk of hemorrhage.^7,⁸ These findings led to approval by the FDA of rtPA, at a dose of 0.9 mg/kg, in acute stroke patients presenting within 3 hours of symptom onset.

Recently, trials have focused on the benefits of rtPA beyond the 3-hour window. The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) trial, published in 1999, evaluated the benefits of rtPA administration between 3 and 5 hours after symptom onset.⁵ This trial demonstrated no benefit to the administration of rtPA beyond 3 hours. In 2004, published pooled data from the ATLANTIS, ECASS, and NINDS trials suggested a potential benefit in administration beyond the 3-hour window.³⁷ In 2008, Hacke et al. demonstrated significant benefit in clinical outcome at 90 days in patients receiving rtPA within 180 to 270 minutes after symptom onset.¹² In 2009, the FDA approved the use of rtPA in acute ischemic stroke in patients 3 to 4.5 hours after symptom onset.

Despite the recent temporal expansion, intravenous rtPA faces several important limitations. Research has demonstrated ineffectiveness in lysing thromboembolic obstruction of large proximal vessels as compared to more distal, smaller vessels.¹⁶ One study of 349 patients undergoing intravenous rtPA for stroke revealed nearly one third with no recanalization, one third with partial recanalization, and only one third with complete recanalization.³⁸ In addition, early reocclusion has been demonstrated in up to 34% of patients receiving intravenous rtPA.^14,¹⁹ To combat these limitations, new endovascular therapies have been developed to provide better targeting of thrombolytic agents with improved recanalization and prevention of reocclusion. These therapies are described in the remaining sections of this chapter.

General Endovascular Procedure

The access area, typically the common femoral artery (the radial artery remains a secondary option), is prepped and draped sterilely. A 5- to 8-French (Fr) sheath is then placed depending on the anticipated device to be utilized. After confirmed, uncomplicated arterial access, a heparin bolus may be administered to maintain an activated coagulation time between 250 and 300 seconds. Some interventionalists aim for a lower activated coagulation time to compensate for planned dosing of intra-arterial thrombolytics and antiplatelet agents and thus potentially reduce the theoretical risk of hemorrhagic transformation. If prior CTA or magnetic resonance angiography (MRA) has been performed (recommended), then selective catheterization of the target vessel can be performed. If CTA or MRA has not been completed, a diagnostic cerebral angiogram guided by patient symptomatology should be performed to localize the occlusion. The interventionalist then assesses the location of arterial occlusion and evaluates for additional arterial pathology (i.e., vessel dissection) prior to intracranial intervention. A microcatheter is then introduced over a microwire and is navigated to the site of arterial occlusion (Fig. 85-2). The microwire is then gently navigated across the occlusion with a twisting motion. Once this is done, the microcatheter is advanced over the microwire to a position beyond the occlusion. A microcatheter angiographic run should then be performed to define the distal aspect of the occlusion. At this juncture, the interventionalist must make a decision regarding the type of intra-arterial intervention that will be undertaken. There are no data published to definitively support the choice of one intervention modality over another. This decision should be guided by the comfort level and experience of the interventionalist with each technique and device, as well as the patient-specific anatomy. Following each endovascular intervention, angiography is performed to observe for vessel recanalization. All catheters and wires are removed upon conclusion of the intervention, and the arteriotomy puncture is sealed using a percutaneous closure device. Alternatively, a flexible sheath may be left in place until serum thrombolytic levels normalize. The patient should be monitored in an intensive care unit with frequent neurologic examinations and strict blood pressure and glucose control.

FIGURE 85-2 Schematic diagram illustrating an occlusive thrombus in the M1 segment of the MCA. The microcatheter is shown just proximal to the occlusion. At this juncture, the microwire is gently navigated across the occlusion with a twisting motion, followed by advancement of the microcatheter over the microwire to a position beyond the occlusion. A microcatheter angiographic run is then performed to define the distal aspect of the occlusion.

Intra-Arterial Thrombolytic Therapy

Intra-arterial thrombolysis utilizes precise localization for administration of thrombolytic agents while minimizing systemic exposure. The agent is administered through an endovascular microcatheter placed at the site of the occlusion. When the region of occlusion is approached, thrombolytics are administered in immediate proximity to the clot, maximizing the effect of the agent at the target while reducing the systemic consequences of circulating thrombolytic agent (Fig. 85-3). Intuitively, early series suggested improved recanalization rates.^39,⁴⁰ These findings prompted the first randomized, controlled trial in intra-arterial thrombolysis, the Prolyse in Acute Cerebral Thromboembolism (PROACT) II trial.⁶ Patients with middle cerebral artery (MCA) occlusion were randomized to 6 mg of intra-arterial recombinant prourokinase (rpro-UK) versus intra-arterial placebo. All patients received intravenous heparin. This trial demonstrated a significant improvement, following administration up to 6 hours after symptom onset, in both recanalization (66% vs. 18%) and functional independence following MCA occlusion. However, intra-arterial rpro-UK was associated with a twofold risk of SICH. Mortality was equivalent between groups. Unfortunately, at this time rpro-UK is unavailable in the United States. Therefore, while providing an exciting proof of concept, these data have not resulted in an available therapy for acute stroke therapy in the United States.

FIGURE 85-3 Schematic diagram depicting intra-arterial thrombolysis. A, The microwire is navigated just proximal to the occlusion. B, The microcatheter is passed over the wire to the occlusion, and intra-arterial thrombolytics are administered. C, Dissolution of the thrombus has occurred with restoration of vessel patency.

The Interventional Management of Stroke II (IMS II) study, published in 2007, was a pilot trial with a planned comparison of the 3-month outcomes of patients treated with a combined algorithm of intra-arterial and intravenous rtPA versus the NINDS intravenous rtPA trial cohorts as historical controls, placebo, and intravenous rtPA groups.¹⁰ The IMS II protocol involved administration of 0.6 mg/kg of intravenous rtPA followed by up to 22 mg of intra-arterial rtPA administered at the site of thrombus by the EKOS microinfusion or standard microcatheters. Outcomes and mortality were significantly better in the intra-arterial group compared to the NINDS placebo group in all categories and trended toward significance compared to the intravenous rtPA cohort in most categories (achieving significance in two global measures). The IMS III trial, a prospective, randomized, controlled trial to further investigate intra-arterial plus intravenous rtPA, is under way.

Mechanical Thrombectomy

The phase 1 results of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 1 study were published in 2004,⁴¹ demonstrating safety and efficacy of a new mechanical thrombectomy device. The Merci Retrieval System (Concentric Medical), a catheter-based retrieval device that physically ensnares the clot and then withdraws it from the site of occlusion, was further evaluated in the MERCI and Multi-MERCI trials that followed.⁴² These studies were single arm and therefore did not allow direct comparison to other therapeutic modalities; however, they suggested improved recanalization rates over either intravenous or intra-arterial thrombolysis. The first-generation MERCI devices, such as the Merci Retrieval System, demonstrated recanalization rates of approximately 50% with clot retrieval alone and 60% when paired with intra-arterial thrombolysis. In addition, benefit was seen up to 8 hours after symptom onset, compared to the 4.5- or 6-hour windows of intravenous or intra-arterial rtPA, respectively. Unlike intravenous or intra-arterial rtPA, mechanical thrombectomy devices do not use potent thrombolytics and therefore represent a useful alternative treatment modality in those patients with thromboembolic stroke who have contraindications to systemic thrombolytic therapy. SICH was comparable to other treatment modalities and has been reported in roughly 7% to 10% of patients. Given its documented efficacy and relative safety, the FDA approved the use of the Merci Retriever in 2004 for revascularization in acute ischemic stroke.

The Merci Retrieval System, the prototype for mechanical thrombectomy devices, is composed of five essential subunits: the balloon guide catheter, the distal access catheter, the microcatheter, the guidewire, and the retrieval device (Fig. 85-4). First, the balloon guide catheter is navigated into the distal cervical arterial vessel. The distal access catheter is then advanced over the microcatheter to a position of stability, preferably at least as distal as the origin of the target vessel. The microcatheter and guidewire are then advanced to the clot. The guidewire is then exchanged for the retriever device, and the retriever is deployed just beyond and within the clot. The retriever device has a natural coiled shape and, when deployed, acquires its coiled shape both distal and within the clot. When the clot is engaged by the retriever catheter, the balloon is inflated and the interventionalist then performs a slow pull and holds while maintaining the position of the distal access catheter relative to the clot. Next, the distal access catheter is secured relative to the microcatheter, and then all units are pulled proximally to the balloon catheter. While this maneuver is performed, aspiration through the balloon guide catheter is performed to minimize the likelihood of reembolization while the clot is withdrawn. Once all units and the clot have entered the balloon catheter, the elements are then removed from the system and angiography is performed to examine for adequacy of recanalization and distal perfusion.

FIGURE 85-4 Schematic diagram depicting the action of the prototypical mechanical thrombectomy device. A, The microcatheter is navigated over a microwire into and beyond the occlusive thrombus. The microwire is then exchanged for the retriever device. B, The retriever device is deployed distal to and within the thrombus and acquires its coiled shape. When the clot is ensnared, the proximal balloon (not pictured) is inflated. C, The microcatheter, retriever device, and clot are withdrawn into the balloon catheter; subsequently, the balloon is deflated, restoring vessel patency.

Newer-generation MERCI thrombectomy devices utilize additional suture elements to improve clot retrieval. Such improvements have been demonstrated in the Multi-MERCI trial to provide roughly 60% recanalization rates when used alone and recanalization rates of nearly 70% when used with intra-arterial thrombolysis.^27,⁴² Trends of improved recanalization, lower mortality, and improved outcomes were demonstrated by the newer devices compared to the prototype device, although these were not statistically significant. No differences in SICH were seen among devices, with all devices having a roughly 7% to 10% risk of clinically significant hemorrhage.

Thromboaspiration

A novel device utilizing a suction catheter was introduced several years after the success of the mechanical thrombectomy devices. The first thromboaspiration device tested, the Penumbra System, was designed for large-vessel intracranial occlusive thrombi. The Penumbra System utilizes a suction catheter and separator to debulk and remove the thrombus piecemeal (Fig. 85-5).

FIGURE 85-5 Schematic diagram depicting the prototypical thromboaspiration device. A, The suction microcatheter is guided over a microwire to the occlusive thrombus. The microwire is then exchanged for the separator device. B, The separator is passed distally into the thrombus, and suction is initiated. The separator is repeatedly advanced into, and withdrawn from, the thrombus. Pieces of freed clot are aspirated proximally into the suction catheter. C, Vessel patency has been restored, and the microcatheter is withdrawn.

The procedure is initiated via standard endovascular cannulation techniques. A guidewire is passed just proximal to the arterial thrombus. Next, a suction catheter is passed over the wire to a position just proximal to the clot. Then, the wire is removed and replaced by a separator microwire. The separator is then passed forward into the thrombus. At this time, the suction is turned on and the separator is repeatedly withdrawn and advanced into the thrombus. As the separator is withdrawn, pieces of thrombus are aspirated into the suction catheter. Finally, after the clot is removed in its entirety, the suction is extinguished. The separator and the suction catheter are then withdrawn.

The initial phase I study of the Penumbra System thromboaspiration catheter demonstrated 100% efficacy in achieving revascularization to TIMI grade 2 or 3 in the 21 patients tested.⁴³ The phase III trial that followed, involving 125 patients from 24 centers, demonstrated an 82% revascularization rate, with 58% achieving an improvement in greater than or equal to 4 points on the NIHSS.⁴⁴ SICH occurred in 11% of patients. After review of the efficacy of this system, the Penumbra System achieved FDA approval in 2008 for revascularization in acute ischemic stroke.

Angioplasty

Angioplasty, alone or with other endovascular therapies, has also demonstrated effectiveness in patients presenting with acute stroke. A pilot study by Nakano et al. in 1998 demonstrated successful recanalization with percutaneous angioplasty (PTA) in 8 of 10 patients with acute MCA occlusion.⁴⁵ These findings led to a trial comparing PTA versus intra-arterial thrombolysis in patients with acute MCA trunk occlusion, in which 36 patients were treated with intra-arterial thrombolytic therapy alone (control group) and 34 patients underwent PTA.⁴⁶ Recanalization rates were 91% in the PTA group versus 64% in the intra-arterial group. In addition, the incidence of symptomatic intracranial hemorrhage was only 2.9% in the PTA group versus 19% in controls.⁴⁶ Other studies have since supported these findings, demonstrating high rates of recanalization, low rates of SICH or systemic bleeding, and significant improvement in neurologic function with combined angioplasty and thrombolysis.^47,⁴⁸ In addition, many investigations have shown the technical feasibility and high efficacy of PTA in acute ischemic stroke,^46,^49,⁵⁰ and it seems to be particularly useful in cases of atherothrombotic disease, in which the residual stenosis may reduce flow sufficiently to lead to rethrombosis.⁵¹

Stenting

Stent placement as a treatment for acute ischemic stroke was introduced primarily as a rescue therapy in combination with other treatments. Investigations into the application of stents in this patient group focused on achieving the high recanalization rate of stenting seen in other physiologic settings while minimizing the risk of SICH through traumatic vessel injury. The development of self-expanding stents and innovations in delivery catheter design for neurointerventional applications has improved the overall safety and deliverability of stent deployment for stroke. One prospective study, the Stent-Assisted Recanalization in Acute Ischemic Stroke trial, analyzed outcomes for patients who underwent primary stenting for stroke.⁵² Of 20 patients presenting within 8 hours of stroke onset, 100% achieved recanalization rates of TIMI 2 or 3. In addition, 60% of patients achieved a modified Rankin score of 3 or less and nearly 50% achieved a score of 0 or 1 at 1-month follow-up.

Temporary endovascular bypass is an attractive method of achieving arterial recanalization without permanent deployment of a stent. This technique involves temporary deployment of a retrievable stent into the affected artery to achieve recanalization, followed by removal of the stent once satisfactory blood flow has been restored. This is an attractive option for patients who cannot tolerate long-term antiplatelet therapy (i.e., active gastrointestinal bleeding). In addition, novel acute stroke treatment devices are in development based on this temporary stent model.

Currently, no phase III trials have been published in either primary stenting or stent-assisted therapy in acute ischemic stroke. However, several small series have been published documenting anywhere from 68% to 92% recanalization rates.⁵²^–⁵⁵ In addition, low SICH and in-stent stenosis rates have been reported. The theoretical benefits of stenting are well described but to this point have only been demonstrated in several small series. These benefits include immediate recanalization, reduced reocclusion rates compared to other techniques, and reduction of distal embolization through displacement of fragments against the vessel wall.