3.1.1 Clinical Presentation

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  A 78-year-old female presented to the emergency department 4 hours after acute onset of left arm and left leg weakness with vertigo symptoms. Clinical examination was suggestive of proximal M1 occlusion and revealed National Institutes of Health Stroke Scale (NIHSS) score of 14.

3.1.2 Imaging Workup and Investigations

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  Noncontrast CT demonstrated hyperdense right M1 (Fig. 3.1).

  
  
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  CT angiography demonstrated corresponding occlusion.

3.1.3 Diagnosis

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  Right M1 occlusion.

3.1.4 Management

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  IV-tPA and suction thrombectomy.

3.1.5 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. 1 mL L/A was utilized for anesthesia.

  
  
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  A right common femoral artery puncture was performed.

  
  
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  A 6-Fr shuttle sheath was placed and attached to a continuous heparinized flush.

  
  
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  A 5-Fr, 125-cm H1H catheter was advanced through the sheath over a guide wire into the left common carotid artery (CCA).

  
  
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  The H1H was used as a coaxial technique to gain access to proximal CCA for the shuttle given the marked proximal tortuosity of the arch.

  
  
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  A 6-Fr neuron was placed into the left ICA. Combination of 0.54 penumbra and prowler superselect was navigated into M1 and was able to traverse the occlusion.

  
  
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  Suction was applied with dissipation of clot and restoration of TICI 3 recanalization (Fig. 3.2).

  

3.1.6 Outcome

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  The catheters were removed. The sheath was removed and Angio-Seal applied. There was good hemostasis. There were no complications.

  
  
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  The patient had a normal recovery and uneventful postprocedural course.

  
  
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  The NIHSS score was 1 at 24 hours and 0 at 30-day follow-up.

  
  
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  On 6-month follow-up, he remained at his functional baseline.

3.1.7 Discussion

The early results of randomized controlled trials (RCTs) comparing conventional intravenous tissue plasminogen activator (IV-tPA) to endovascular methods, including intra-arterial (IA) tPA and mechanical thrombectomy, were anything but promising. In 2013, the publications of the three negative trials (IMS III, SYNTHESIS, and MR RESCUE) cast a shadow over the future of endovascular thrombectomy.

The IMS III was an international phase III RCT comparing endovascular therapy plus IV-tPA to IV-tPA alone in patients who have received tPA within 3 hours of stroke onset and with an NIHSS score ≥10. The trial was conducted in the United States, Canada, Australia, and Europe. The study randomized in a 2:1 fashion with 434 patients receiving the endovascular therapy and 222 patients receiving only IV-tPA, but was stopped early due to futility. At its termination, there were no significant differences observed in overall good clinical outcome (as defined by modified Rankin scale [mRS] ≤ 2), good clinical outcome in subgroup analyses of NIHSS score above 20, good clinical outcome in subgroup analysis of NIHSS score below 19, and mortality at 90 days or symptomatic hemorrhage rates. ¹ While the result of the trial was negative, the investigators as well as critics recognized the limitations of IMS III.

A number of factors could have contributed to the negative outcome, one of which is long mean time from symptom onset to reperfusion. In an analysis of the data from IMS III, clinical outcomes were correlated with perfusion times. In particular, every 30-minute delay was correlated with a 12% reduction in the relative likelihood of good clinical outcome. ² Conversely, with a decrease in reperfusion time, there would be greater chance of having a good clinical outcome. Another factor that provoked criticism was the use of outdated mechanical thrombectomy devices. The trial included the use of many endovascular treatment methods such as MERCI, Penumbra, or IA-tPA with EKOS or the standard catheter, with only a small proportion of Solitaire before study termination. ¹ While the first-generation devices were shown to be safe and efficacious, the stent retrievers (i.e., Solitaire and Trevo) consistently proved to achieve greater recanalization rates and have better clinical outcomes. The predominant use of first-generation devices did not reflect the full potential of endovascular therapy at the time. Finally, over the course of the study, a baseline computed tomography angiography (CTA) became the standard of care for patients with acute stroke. Thus, over half of the patients enrolled in the study did not have a confirmed diagnosis of a large artery occlusion on CTA. ¹ Thus, the study included many patients who were unlikely to benefit from endovascular therapy. Taken together, the delay in reperfusion time, use of older generation devices, and lack of CTA at baseline contributed to the negative outcome of the IMS III trial.

The SYNTHESIS trial took a different approach and compared endovascular therapy alone with IV-tPA alone. The study was a multicenter trial conducted in Italy. In this trial, 362 patients within 4.5 hours of stroke onset were randomized to either endovascular therapy or IV-tPA in a 1:1 ratio. Endovascular therapy involved IA-tPA or mechanical thrombectomy (Solitaire, Trevo, MERCI, and Penumbra), but no IV-tPA was administered to this group. The primary end point of an excellent clinical outcome (mRS ≤ 1) was not significantly different (30.4% for endovascular group and 34.8% for IV-tPA group). There were no significant differences in symptomatic hemorrhage occurrences, other serious adverse events, or the case fatality rate between the two arms. ³

The limitations of SYNTHESIS were similar to those of IMS III. There was a 1-hour delay between treatment with endovascular therapy and IV-tPA (3.75 vs. 2.75 hours, respectively). As mentioned earlier, symptomatic stroke to therapy time is critically important to ensure good clinical outcome, and the delay in therapy time likely minimized the effects of endovascular therapy. The newer generation of stent retrievers was again underutilized in this study. Out of those who ultimately received endovascular therapy, the majority of patients (66%) were treated with IA-tPA, and only 14% were treated with the stent retrievers. Lastly, CTA or magnetic resonance (MR) angiography was not an inclusion criterion for endovascular therapy, due to the lack of availability of these image modalities at the start of the trial. Thus, patients who underwent endovascular treatments did not have a confirmed large artery occlusion. All of these limitations undermined the effectiveness of endovascular therapy, contributing to the trial’s negative result. ³