A 70-year-old man develops sudden difficulty speaking and right-sided weakness last seen normal 90 minutes prior to hospital arrival. At the hospital, the patient is completely aphasic and right hemiplegic with a gaze preference. A CT of the head without contrast shows no evidence of intracranial hemorrhage, and CT angiogram of the patient’s cervico-cerebral vasculature shows a left intracranial internal carotid artery occlusion. His National Institute of Health Stroke Scale (NIHSS) score is 24, indicating a severe stroke. The patient is immediately started on intravenous tissue plasminogen activator (I.V. t-PA). He is rushed to the endovascular suite. Within 15 minutes, the neurointerventionalist has obtained femoral access with a standard 8 French access kit.

An 8 French, 90-centimeter balloon guide catheter is placed directly into the intracranial internal carotid artery using fluoroscopy. Next, a microcatheter is manipulated over a micro-guidewire across the occlusion until it is distal to the thrombus. The microwire is removed, and a stent retriever device is advanced through the microcatheter and across the thrombus. The microcatheter is withdrawn, unsheathing the stent so that it can expand and engage the thrombus. Flow into the carotid is occluded by inflating the balloon guide catheter. Continuous aspiration from the guide catheter is initiated to remove clot fragments that could detach from the device and the stent. The stent along with the clot and the microcatheter, is retracted into the guide catheter and out of the body.  A follow-up angiographic run demonstrates complete reperfusion into the internal carotid artery, only ten minutes after femoral arterial access.

Seven hours post-procedure, the neurointerventionalist greets the patient. The patient can speak intelligently and fluently, track with his eyes, and lift up his arms and legs without any drift. He smiles with only a slight facial droop and his NIHSS score is now 2.

Many medical students have probably learned about the use of I.V. t-PA as the standard ischemic stroke treatment, but may not be as familiar with the use of mechanical thrombectomy as a treatment modality. Mechanical thrombectomy is the use of endovascular devices to remove blood clots that are blocking blood flow.  It is a major advancement in the treatment of ischemic stroke and a life-saving procedure in appropriately selected patients. Mechanical thrombectomy is performed in ischemic stroke patients with an emergent large vessel occlusion (ELVO), which comprise one-third of ischemic stroke patients that present to the emergency department within 6 hours of symptom onset [1].

The cervico-cerebral large vessels include the anterior cerebral arteries, the middle cerebral arteries (MCA) and its major branches, the basilar artery and the internal carotid arteries. Large vessel occlusions have a poor response to I.V. t-PA and have a high mortality rate—MCA occlusions have a 28% mortality rate and basilar artery occlusion mortality rates can reach 90% [2-3].  Initially, randomized controlled trials, such as IMS III, MR RESCUE and SYNTHESIS Expansion, investigating mechanical thrombectomy versus the standard of care (I.V. t-PA) showed no clear benefit between the treatments [4-6]. Many were surprised by these results. Neurointerventionalists were sure that mechanical thrombectomy provided a beneficial treatment option for certain ischemic stroke patients; they had seen these patients markedly improve post-procedure. Many reasons exist for why these trials did not demonstrate that mechanical thrombectomy was superior to the standard of care. These trials used thrombectomy devices that were still evolving at the time—the pioneering MERCI Retrieval System™ was one such device. The MERCI Retrieval System™ is essentially a wire with a corkscrew, making it quite cumbersome to use and difficult to deploy safely.

The MERCI Retrieval Device with a clot at its end

A lack of appropriate patient selection may have also led to negative results. For example, in the IMS III trial, only 47% of patients had a baseline CT or MR angiography performed to document a large vessel occlusion—meaning some patients who underwent treatment did not necessarily have a large vessel occlusion [4]. An important concept we all know now is that time equals brain! Every 30-minute delay in reperfusion reduces probability of a good outcome by 10% [7]. Yet, in the IMS III Trial, the mean time to reperfusion was 325 minutes, likely due to the inability to get patients to endovascular management as quickly as possible at many of the centers [7]. In addition, treatment protocols were not completely standardized among centers in some of these trials [4-7].

The field has been advanced by further development in stentrievers, which are now the standard mechanical thrombectomy device. These devices are stents at the end of a wire that expand within a clot and then retract into the guide catheter to retrieve the clot from the circulation. These devices appeared to perform better than the MERCI Retrieval System™ and older thromboaspiration vacuum devices. Ischemic stroke trials using the newer stentriever devices, with better patient selection, were developed. 2015 marked a huge year for endovascular stroke therapy, as the results of multiple endovascular trials were released and all showed positive results [8-12]. The selection criteria of these trials all varied to some degree but had unifying features. Most trials only included patients with a maximum of 6 hours since the onset of the stroke and virtually all trials had confirmed large vessel occlusion on CT or MR angiography. A meta-analysis pooled the results of these five trials and the results were very convincing. Endovascular thrombectomy led to significantly reduced disability (measured by modified Rankin Score < 2) at 90 days compared with control, which was the primary endpoint in these studies [13]. Fifty percent of patients treated with mechanical thrombectomy had early neurological recovery 24 hours post-procedure versus only 21% in the control population [13]. Twenty-one percent of patients had an NIHSS score of 0-2 twenty-four hours post-procedure versus only 8% in the control population [13]. These results spawned the creation of the American Heart Association/American Stroke Association 2015 guidelines which made endovascular treatment the standard of care for ischemic stroke cases with internal carotid or M1 occlusions that meet specific criteria (Class level 1A) [14].

The DAWN and DEFUSE 3 trials are the latest victories for mechanical thrombectomy. These trials analyzed outcomes of delayed reperfusion with mechanical thrombectomy (over 6 hours last seen normal) and required that large vessel occlusions with a small core infarct and a large penumbra (area of at-risk but salvageable tissue) to be identified via vascular perfusion imaging before admitting patients into the trials. The results of DAWN demonstrated that mechanical thrombectomy improves outcomes up to 24 hours since the onset of symptoms with the number needed to treat at only 2.8! [15]. The DEFUSE 3 trial concluded that mechanical thrombectomy plus standard medical therapy for ischemic stroke 6 to 16 hours after a patient was last seen normal resulted in better functional outcomes 90 days after stroke compared to standard medical therapy alone in patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted as identified by vascular perfusion imaging [16].

Current efforts are now directed at finding ways to increase the pool of patients who can receive this beneficial therapy, further develop systems of care that decrease the time to treatment, and to standardize technical aspects of the mechanical thrombectomy procedure [17].

Written by Kunal Karani, MS4, with Guidance from Aaron Grossman, MD, PhD at the University of Cincinnati College of Medicine

References:

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