2.1.1 Clinical Presentation

A 67-year-old female with known atrial fibrillation (AF) presented with acute onset of speech disturbance and right-sided weakness. On admission, her clinical examination revealed global aphasia, right hemiplegia, right hemianopia, and eye deviation to the left, suggestive of left middle cerebral artery (MCA) syndrome. Her initial National Institutes of Health Stroke Scale (NIHSS) score fluctuated between 14 and 18.

2.1.2 Imaging Workup and Investigations

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  Noncontrast computed tomography (CT) was performed.

  
  
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  CT perfusion demonstrated distal M1 occlusion. Occluded right internal carotid artery (ICA) and anterior circulation supply predominantly via the left ICA/ACOM. Small posterior communicating arteries (PComms) bilaterally. CTP revealed mismatch with a small insular region of infarct.

  
  
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  CT angiography revealed occlusion of distal M1 segment of the left MCA (Fig. 2.1).

  

2.1.3 Diagnosis

Distal M1 occlusion in the context of a patient with AF. Mechanism of embolus was thought to be cardioembolic based on warfarin being stopped and the presence of known AF.

2.1.4 Management

Mechanical thrombectomy of distal M1 segment with MERCI clot retrieval device.

2.1.5 Technique

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  The patient was prepped and draped in the usual sterile fashion.

  
  
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  The right common femoral artery was localized by palpation. A right common femoral artery puncture was performed.

  
  
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  A 6-Fr shuttle and 125-cm H1H were used to access the left ICA.

  
  
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  A mid position was adopted because of an ICA loop.

  
  
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  A combination of MERCI microcatheter and Xpedion wire was used to gain access beyond the clot.

  
  
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  Two attempts at clot withdrawal were attempted. Resistance was encountered at the ICA terminus such that the shuttle was being pulled forward on sustained backward tension.

  
  
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  The clot was shown to be at the ICA terminus on a run performed in this position.

  
  
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  Vasospasm and vessel distortion of ICA were seen.

  
  
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  With continued sustained tension, the MERCI device straightened and the clot returned to its distal location.

  
  
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  A 3 mg of intra-arterial (IA) tPa was administered during the procedure at various times both in and beyond the clot.

  
  
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  A final attempt at 6 hours post onset to deploy a hyperform balloon was unsuccessful due to looping in the cavernous segment of the ICA. A final cerebral angiography revealed no significant change in clot position. The puncture site was closed with Angio-Seal.

2.1.6 Outcome

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  Patient made significant recovery, with NIHSS score decreased to 2 following the procedure. Her NIHSS score at 30 days was 1.

2.1.7 Discussion

Around the same time, IA tissue plasminogen activator (tPA) was being tested for its efficacy in the treatment of acute ischemic stroke, and mechanical thrombectomy was being developed as an adjunctive or alternative measure. Mechanical thrombectomy involves entering the vessel directly to the position of the clot and then removing it by either retrieving the clot distally or proximal aspiration.

The first mechanical thrombectomy system to be approved by the Food and Drug Administration (FDA) is the MERCI Retriever System. ¹ This system consists of a nitinol wire that is passed through a catheter distal to the thrombus. When the catheter is removed, the wire assumes a corkscrew shape at its tip. Thereafter, withdrawal of the wire allows the clot to become free. Its safety and efficacy were examined by the MERCI trial. This was a prospective study with patients with contraindication to tPA, or had stroke duration longer than the 3-hour window of intravenous (IV) tPA. Out of the 151 patients who received the MERCI retriever, 69 achieved recanalization in the intention to treat analysis, giving a recanalization rate of 46%. This can be compared to the placebo arm of PROACT-II trial that had a recanalization rate of 18%. However, the rate of MCA recanalization was 45%, less than the 66% reported in PROACT-II using IA prourokinase. The SICH rate was estimated to be 5%, which is higher than that of the placebo arm of NINDS and PROACT-II, but comparable to IV-tPA in the NINDS trial, IA/IV-tPA in the IMS trial and IA prourokinase in PROACT-II. Clinical significant complication rate was 7.1%, again comparable to these historic trials. The overall mortality was high at 44%, due to the patient selection for those with severe strokes and large vessel occlusions. ¹ Overall, the results of the MERCI trial suggest that the MERCI retriever is a safe and efficacious alternative for patients with contraindications to tPA or stroke duration outside of the tPA treatment window. ² While the MERCI trial was underway, advancements were made to the retriever system, and the newer generation of L5 MERCI retriever was tested in the Multi-MERCI trial. Successful recanalization rate was higher with this new version of MERCI retriever (57.3%). Favorable outcomes, defined as modified Rankin scale (mRS) ≤ 2 at 90 days, were achieved in 36% of the patients. The SICH (9.8%) and procedure-related complication rate (5.5%) were again comparable with other stroke trials. ³ The MERCI device was proven to be safe and efficacious by the MERCI and the Multi-MERCI trials, starting a new exciting era of mechanical thrombectomy.

Another mechanical thrombectomy device similar to the MERCI retriever was the CATCH device, a nitinol wire construct that assumes the shape of a basket when pulled out of the catheter. A retrospective case series examined the use of CATCH in 40 patients, most of who received IV-tPA. The recanalization rate was 65% and favorable clinical outcome of mRS ≤2 was 39%. Additionally, the SICH rate was 18% and procedural complication rate was 15%. These outcomes were all comparable to the MERCI and the PROACT-II trials. ⁴

Then in 2010, the new generation of stent retrievers came into existence, the first of which was named Solitaire. The device contains a stent that is deployed within the thrombus. This allows the stent to expand into the thrombus, thus entrapping it within. The clot is removed when the stent is withdrawn from the vessel. The SWIFT trial compared patient outcomes with the MERCI device. The results vastly favored the new stent retrievers, with recanalization rate of 64% in comparison to the 24% recanalization rate achieved using MERCI. Good 90-day neurological outcomes were also achieved more frequently in the Solitaire group than in the MERCI group (58 vs. 33%). Similarly, the use of Solitaire also resulted in less mortality (29 vs. 69%). The SWIFT trial highlighted the vast improvement of the Solitaire stent retriever device over MERCI. ⁵ The technique and devices of mechanical thrombectomy were ever improving.

Other stent retrievers came into existence around the same time. The Trevo and Revive devices are similar to the Solitaire device, with the exception that Revive employs a closed basket at the end for better clot removal. ^{6 ,​ 7 ,​ 8} Their safety and efficacy were tested in prospective studies and randomized controlled trials (RCTs). The TREVO study was a single-center prospective trial with 60 patients receiving the Trevo device within 8 hours of stroke onset in the anterior circulation and within 12 hours of onset in the posterior circulation. The recanalization rate was 73.3% with Trevo alone, and went up to 86.7% when IA-tPA or other devices were used additionally. Good outcome as defined by mRS ≤2 was 45% at 90 days. Mortality was 28.3% and SICH was 11.7%. The Trevo device was further compared to the MERCI device in TREVO 2, an RCT with 88 patients receiving treatment with Trevo and 90 patients receiving MERCI. Recanalization was achieved in a greater number of patients treated with Trevo than with MERCI (86 vs. 60%). In addition, more patients achieved a good functional outcome (mRS ≤ 2) in the Trevo group when compared to the MERCI group (40 vs. 22%). ⁷ The Revive device was examined in the small scale REVIVE study. Vessel recanalization was successful in all patients who received Revive and 60% of patients achieved a clinical improvement of greater than 8 points on the NIHSS or a NIHSS score of 0 to 1. ⁸ The results of SWIFT, TREVO, TREVO 2, and REVIVE provided evidence for the safety and efficacy of this new generation of mechanical thrombolytic devices. All stent retrievers achieved better recanalization rates and clinical outcomes than the older MERCI-type devices, and were shown to be equally safe.

As early as 2008, the FDA gave approval to Penumbra, a mechanical thrombolytic device that works by aspirating the clot proximally. This device first breaks up the clot into smaller pieces, then uses both aspiration and direct extraction to remove it from the vessel. ⁹ The safety and efficacy of the device were assessed in three single-arm studies: SPEED, Pivotal, and POST. ^{9 ,​ 10 ,​ 11} In these studies, revascularization rate ranged from 81.6 to 91%, and good clinical outcome of mRS ≥ 2 at 90 days ranged from 25 to 40%. The rate of SICH was 11.2 and 14% in the Pivotal and SPEED studies, respectively, and the rate of serious procedure-related adverse events was 5.7% in the POST study. All-cause mortality ranged from 20 to 32.8%. The Pivotal, SPEED, and POST studies proved that Penumbra is both an efficacious and safe device, but these were single-arm studies without comparison to other devices or treatment options. ^{9 ,​ 10 ,​ 11}

Throughout the years, there has been a wide range of mechanical thrombectomy devices developed, including the distal clot removal devices (MERCI and Catch), the stent retrievers (Solitaire, Trevo, and Revive), and the aspiration device (Penumbra). Each of these were examined in studies and proven to be efficacious and safe. These mechanical thrombectomy devices along with IA-tPA had shifted the focus of acute ischemic stroke management from bedside infusion of IV-tPA to the neuroangiography suite. However, the clinical effectiveness and safety of these endovascular treatments still needed to be compared with the effectiveness of IV-tPA in RCTs.