30.1.1 Clinical Presentation

A 57-year-old male presents to the emergency department (ED) 180 minutes after sudden onset of left arm and leg weakness as well as facial droop. Clinical examination confirms a right middle cerebral artery (MCA) syndrome, with a National Institutes of Health Stroke Scale (NIHSS) score of 17.

30.1.2 Imaging Workup and Investigations

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  Noncontrast computed tomography (NCCT) performed shortly after presentation to the emergency department (200 minutes after symptoms onset) showed no early infarction, with an ASPECTS score of 10.

  
  
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  CT angiography (CTA) showed occlusion of the M1 segment of the right MCA and moderate collateral circulation.

  
  
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  CT perfusion (CTP) showed increased mean transit time (MTT) in the right MCA cortical branch territories, with mildly reduced cerebral blood flow (CBF) and normal cerebral blood volume (CBV), indicating tissue at risk of infarction, but potentially salvageable with reperfusion.

30.1.3 Diagnosis

Right M1 occlusion without early infarction in the MCA territory and large ischemic penumbra (mismatch on CTP).

30.1.4 Management

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  The patient had no contraindication to intravenous thrombolysis based on clinical history, clinical assessment, and CT findings.

  
  
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  He received an initial bolus and infusion of a full dose of intravenous tissue plasminogen activator (IV-tPA), commencing 220 minutes after symptom onset. Endovascular therapy was considered appropriate, based on time from onset of symptoms, location of the arterial occlusion and CT findings, suggesting potentially salvageable tissue. He patient was brought to the angiography suite and groin puncture was performed 235 minutes after onset of symptoms.

30.1.5 Endovascular Treatment

30.1.6 Postprocedure Care

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  The patient was transferred to the intensive care unit (ICU).

  
  
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  After the thrombectomy procedure, a NCCT was performed to rule out intracranial hemorrhage. The NCCT did not show hemorrhagic transformation (Fig. 30.7).

  
  
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  The patient was loaded with clopidogrel 600 mg plus aspirin 325 mg for the first 24 hours immediately after the procedure.

  
  
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  The patient was closely monitored with subsequent improvement in neurological status over 24 hours. Repeat NCCT 24 hours later showed small infarct in the posterior MCA cortex territory.

  
  
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  After 24 hours, the patient was loaded with a second loading dose consisting of clopidogrel 300 mg plus aspirin 325 mg. After 48 hours, clopidogrel 75 mg plus aspirin 325 mg for 6 weeks. Then, clopidogrel 75 mg plus aspirin 81 mg for 6 months. Finally, aspirin 81 mg lifelong.

  
  
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  A repeat of NCCT 48 hours later showed no further infarct extension or hemorrhagic conversion.

  

30.1.7 Outcome

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  Right MCA occlusive stroke.

  
  
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  Reperfusion therapy with IV-tPA and rescue permanent self-expanding stent placement, following failed mechanical thrombectomy.

  
  
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  Final infarct volume based on day 4 NCCT remained largely similar to the initial 24 hours of NCCT, and significantly smaller than the predicted infarct on CTP.

  
  
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  The patient was discharged 4 days after admission to a rehabilitation hospital, with a modified Rankin scale (mRS) score of 2.

  
  
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  Follow-up CTA at 6 weeks showed stent patency.

30.1.8 Background

Mechanical thrombectomy using a stentriever device has become the standard of care for acute large-vessel occlusions in the anterior circulation. ^{1 ,​ 2 ,​ 3 ,​ 4 ,​ 5 ,​ 6 ,​ 7 ,​ 8} Successful reperfusion (modified TICI [mTICI], 2b–3) is the most powerful predictor of a favorable clinical outcome (mRS score of ≤2 at 3 months). ^{1 ,​ 2 ,​ 3 ,​ 4 ,​ 5 ,​ 6 ,​ 7 ,​ 8} Nevertheless, thrombectomy may not accomplish recanalization in all patients. Arterial reocclusion rate in those five successful trials was 28.9%. ^{1 ,​ 2 ,​ 3 ,​ 4 ,​ 5} New scientific evidence suggests that there is a technical failure rate of 14 to 41% whether using a stentriever with a BGC, distal aspiration catheter, or a combination of devices and techniques. ^{2 ,​ 3 ,​ 4 ,​ 5 ,​ 6 ,​ 7 ,​ 9 ,​ 10 ,​ 11 ,​ 12 ,​ 13 ,​ 14 ,​ 15}

Mechanical thrombectomy may fail due to technical and/or patient factors (see Chapter 29). A failed stentriever technique may be due to a fibrin-rich clot, calcified clot, or an underlying arterial atherosclerotic stenosis. ^{21 ,​ 22 ,​ 23} Procedural time, number of stentriever passes, tandem occlusions of cervical artery and intracranial artery, severe arterial tortuosity, physical properties of the clot, ¹⁶ and pathomechanism of the artery occlusion ¹⁷ are crucial for the success of the mechanical thrombectomy. Longer procedural times, extending beyond 90 minutes, and multiple device passes are associated with worse outcomes. ^{18 ,​ 19} A recent study showed that more than three passes of stentriever is an independent predictor of parenchymal hematoma in acute ischemic stroke and a trend toward a worse clinical outcome. ²⁰ Furthermore, recanalization failure postthrombectomy is well described in cases of intracranial atherosclerotic disease. ²³ Although this is relatively rare in Caucasian populations, it may account for a third of proximal intracranial occlusions among Asians. ^{24 ,​ 25} The presence of a thrombus on presentation CTA can mask an underlying atherosclerotic plaque and/or stenosis. Moreover, use of a stent-retriever in these cases can cause endothelial damage to an underlying atherosclerotic plaque or dissection, leading to thrombus formation and reocclusion.

The natural history of arterial reocclusion in acute ischemic stroke patients is poor. In the REVASCAT trial, 54% of patients with successful reperfusion assessed at 24 hours achieved functional independence compared with only 29% without successful reperfusion. ¹ Comparably, in the SWIFT PRIME trial, 70% of patients with arterial patency, assessed at 27 hours, had achieved functional independence compared with only 18% in those with lesser degrees of patency. ⁴ A number of studies have assessed the outcome in cohorts of patients with arterial reocclusion, whose favorable outcome rate is 16.6 to 22%. ^{26 ,​ 27}

Successful recanalization in large vessel occlusive stroke is associated with a favorable outcome. In cases of mechanical thrombectomy failure due to device–clot interaction, or underlying arterial stenosis, alternative strategies are necessary. One possible technique is the intra-arterial infusion of thrombolytics or glycoprotein IIb/IIIa inhibitors. The catheter delivery of thrombolytics, such as tPA or urokinase and/or antiplatelets as glycoprotein IIb/IIIa inhibitors, can promote successful recanalization in some refractory stroke cases. ^{27 ,​ 28 ,​ 29 ,​ 30 ,​ 31 ,​ 32} Other rescue techniques have also been described, such as angioplasty, ³³ crossing Y stentriever thrombectomy, or a combination of techniques like stent retriever and aspiration catheter thrombectomy (“Solumbra”). ³⁴ Data regarding the efficacy of these approaches is, however, limited to a small series. ^{35 ,​ 36}

Placement of a permanent, self-expanding stent has been suggested both as a primary approach and a rescue tool for the recanalization of an acute large vessel occlusion. ^{27 ,​ 37 ,​ 38} As mentioned above, the refractoriness of a large artery occlusion might occur in different scenarios. In the case of an intracranial atherosclerotic stenosis occlusion, the problem is mainly due to arterial reocclusion. ^{29 ,​ 38 ,​ 39} A glycoprotein IIb/IIIa inhibitor may help prevent such repeated arterial occlusion.

Intracranial atherosclerotic steno-occlusions are often refractory to glycoprotein IIb/IIIa inhibitors, which may be due to endothelial damage, plaque rupture, and/or dissection during stent-retriever mechanical thrombectomy. In these cases, permanent stenting combined with a glycoprotein IIb/IIIa inhibitor has been shown to achieve recanalization and reperfusion in some series. ^{27 ,​ 29 ,​ 30 ,​ 37 ,​ 38 ,​ 39 ,​ 40 ,​ 41 ,​ 42 ,​ 43 ,​ 44 ,​ 45} Baek et al ²⁷ demonstrated that permanent stenting following a failed stentriever thrombectomy may be safe and effective. They retrospectively evaluated 208 patients who underwent stentriever thrombectomy for anterior circulation large artery occlusion between September 2010 and September 2015. Unsuccessful mechanical thrombectomy occurred in 45 of 208 patients (21.6%), with 17 undergoing permanent stent placement and 28 without stent placement. Although it is unclear how the authors determined which patients were stented, 83.3% of stented patients had mTICI 2b–3. In addition, stented patients had significantly more favorable outcomes (mRS of 0–2, 35.5%) and less cerebral herniation (11.8%) than the nonstented patients (mRS of 0–2, 7.1%; cerebral herniation, 42.9%). Symptomatic intracranial hemorrhage (SICH) and mortality rates did not differ between groups (symptomatic hemorrhage and mortality, 11.8 and 23.9%, respectively, in the stented group vs. 14.3 and 39.4%, respectively, in the nonstented group). Solitaire AB was used in 10 patients, and Wingspan stent was used in seven patients. Among 17 stented cases, only 40% underwent balloon angioplasty. A retrospective analysis of the cohorts of 16 comprehensive stroke centers between September 2010 and December 2015 by Chang et al ⁴⁶ concluded that rescue stenting was independently associated with good outcomes without increasing SICH or mortality. In a meta-analysis of seven retrospective studies and one prospective study of rescue stenting for failed mechanical thrombectomy in 160 patients by Wareham et al, ¹¹ the authors found that permanent self-expanding stent placement as a rescue procedure is associated with mTICI 2b–3 in 71% and 90-day mRS of 0 to 2 in 43%. ¹¹ The Solitaire stent (Medtronic) was the most commonly deployed stent following failed thrombectomy attempts (66%; 95% confidence interval [CI]: 31–89%). Pre- or poststent angioplasty was performed in 39% of patients (95% CI: 29–48%).

The advantage of using a self-expandable stent is that it adapts itself to the shape and diameter of the injured artery and minimizes the trauma inflicted on the vessel wall. The Solitaire AB (Medtronic) has been the most frequently used stent in published studies to date. ^{26 ,​ 27 ,​ 46 ,​ 47 ,​ 48 ,​ 49 ,​ 50 ,​ 51} The Solitaire AB (Medtronic) is a nitinol closed cell stent, which is easy to deploy and can be re-sheathed if necessary. The radial force of this stent is often enough to keep a vessel open; however, angioplasty may be necessary in some cases. Recrossing the stent and performing an angioplasty can be challenging, especially in the setting of intracranial atherosclerotic steno-occlusion, as suboptimal angioplasty has been shown to be associated with acute in-stent thrombosis. ²³ Krischek et al ⁵² compared in vitro physical features and functional properties of different self-expanding intracranial stents. They showed variable results dependent on the test method used. However, irrespective of method, the open cell Wingspan stent (Stryker Neurovascular) showed greater radial force compared to the closed cell Enterprise stent (Johnson and Johnson), Solitaire AB, and open cell Neuroform Atlas (Stryker Neurovascular) stents. ⁵² The Solitaire AB showed greater radial force at higher oversizing, whereas the Neuroform Atlas showed greater radial force at lower oversizing. ⁵² No comparative study exists on the safety and efficacy of different self-expanding intracranial stents available. Stent selection may depend on physical and anatomical factors of each individual patient. Knowledge of the stent characteristics, procedural experience, and proper technical skills are mandatory for safe and successful endovascular treatment on the basis of individualized decision making.

A key consideration in choosing between permanent stent deployment and aborting a failed mechanical thrombectomy is the need for platelet inactivation. ²⁹ Heparinization and long-term dual-antiplatelet therapy are necessary during and after stent placement. In addition, platelet inactivation is necessary during the procedure, with some authors starting a GPIIb/IIIa infusion just prior to stent placement, while others prefer loading doses of aspirin and clopidogrel. Regardless of the regimen, the additional blood thinners and degree of anticoagulation needed increases the risk of intracranial bleeding in an acute stroke setting.

Although recent studies affirm that the benefit of achieving a complete recanalization with intracranial stenting compared to failed stentriever thrombectomy with nonrecanalization, ^{27 ,​ 30} there is a vast majority of retrospective studies with selection biases likely present. In the meta-analysis by Wareham et al, ¹¹ the SICH rate was 12%. This rate is similar to recent real-world published rates of SICH in stentriever registries, ⁵³ but higher than those seen in the mechanical thrombectomy randomized trials (0–8%). ^{1 ,​ 2 ,​ 3 ,​ 4 ,​ 5 ,​ 6 ,​ 7 ,​ 8} Many of the patients included in the meta-analysis were treated with thrombolytics prior to stent deployment, which may have increased the bleeding rate (89% of patients were treated with glycoprotein IIb/IIIa inhibitors and 95% had antiplatelet therapy with postprocedure). The data regarding the safety of glycoprotein IIb/IIIa inhibitors are controversial. Recent registry data suggest that postprocedural dual-antiplatelet treatment is safe in the context of large vessel occlusion and cervical ICA stenting ⁵⁴ with no significant increase in SICH but with more favorable recanalization rates. The use of NCCT to assess for contrast staining in areas of core infarct postprocedure might guide the use of antiplatelet therapy after stent placement.

Long-term stent patency is also a concern and necessitates close follow-up. Data governing this cannot be gleaned from big prospective studies. However, mid-term angiographic follow-up was obtained following the small, prospective SARIS trial. ³⁷ Among all the survivors, none developed an in-stent stenosis of greater than 50%.

In conclusion, recanalization failure is not uncommon during mechanical endovascular procedures. The natural history of patients with large vessel occlusion acute ischemic stroke and failed thrombectomy is poor. Permanent self-expanding stent placement appears to be a promising and reasonable approach following the failure of a stentriever and aspiration thrombectomy, if the procedural time is extending beyond 90 minutes or over three passes with no progress; however, the size of core infarct and time from stroke onset should be considered in light of the need for anticoagulation during and after stent placement. Optimal stent device and antiplatelet regimen remain to be elucidated. A prospective registry of patients undergoing rescue stenting would be a useful project to obtain further evidence in order to guide future recommendations.