**5. Endovascular Mechanical Thrombectomy**

In 2005, the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial revolutionized the way ischemic strokes are managed [56]. This was the first study that showed how endovascular embolectomy using a first generation device can improve outcomes of ischemic stroke [56]. The MERCI trial used the embolectomy device (Merci Retriever) for patients who presented within 8 hours of onset of stroke and were otherwise ineligible for intravenous tPA administration [56]. The study showed that recanalization was achieved in 48% of patients who underwent embolectomy and the risk of intracranial hemorrhage was significantly lower, only 7.8%, in comparison to 10% in the PROACT II study [56]. In 2008, after the development of the Merci Retriever the Penumbra System was developed. The Penumbra device is a second generation thrombectomy device that is inserted all the way through the clot followed by application of mechanical aspiration with the use of a suction pump [39]. By using the Penumbra System partial to normal reperfusion was achieved in 81.6% of patients, a percentage higher than that achieved by using the Merci Retriever [56, 57]. Intracranial hemorrhage was observed in 28% of patients on post procedural 24 hour CT scan however only 11.2% were symptomatic [57]. Despite the increase in intracranial hemorrhage observed with the Penumbra device in comparison to the Merci Retriever the 90-day mRS of less than or equal 2 was similar between the two groups, with 25% for the Penumbra system and 27.7% for the Merci Retriever [56, 57]. Shortly thereafter stent retrievers were developed for the use as thrombectomy devices.

In 2012, a third generation mechanical thrombectomy device was introduced. The Solitaire Flow Restoration device versus the Merci Retriever in patients with acute ischemic stroke was studied [58]. The SWIFT study was a randomized, parallel-group, non-inferiority trial that showed that Solitaire Flow Restoration

#### *The History of Neurosurgical Management of Ischemic Stroke DOI: http://dx.doi.org/10.5772/intechopen.95477*

device is significantly better than the Merci retriever device [58]. In particular, patients treated with the Solitaire Flow Restoration device had a rate of recanalization of 61% in comparison to 24% in those treated with the Merci Retriever device [58]. With the use of the Solitaire flow restoration device the rate of symptomatic intracranial hemorrhage was decreased and the overall neurological outcomes were better [58].

Another area of interest was whether devices that combined direct aspiration with thrombectomy would be beneficial in the management of ischemic stroke. The MAX reperfusion catheters as well as a direct aspiration first pass technique (ADAPT) enabled direct aspiration with thrombectomy [53]. In 2018, a randomized controlled study aimed to determine whether there was a difference in ischemic stroke outcomes when the novel 3-dimensional (3-D) stent retriever was used in conjugation with an aspiration-based mechanical thrombectomy device (Penumbra System; Penumbra) versus the aspiration-based thrombectomy alone [59]. The results of the study showed that 87.2% in the 3-D stent retriever with aspiration group versus 82.3% in the aspiration based thrombectomy alone group had a mTICI of 2–3 [59]. The 90-day mRS score of 0 to 2, device-related serious adverse events and procedure-related serious adverse events were similar between the two groups [59].

The next step in the management of acute ischemic stroke was to determine whether endovascular thrombectomy was superior to standard medical care alone [60]. There were five key randomized control studies that aimed to answer this question: MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA [61–65].

The MR CLEAN trial aimed to determine whether patients who presented within 6 hours after onset of ischemic symptoms and proximal intracranial occlusion of the anterior circulation would benefit from mechanical thrombectomy [61]. In particular, all patients in the study received intravenous tPA and were subsequently randomized to receive either intraarterial treatment or not [61]. The study showed that there was improvement in functional independence in the treatment group but no changes in mortality or the occurrence of symptomatic intracerebral hemorrhage between the two groups [61].

The ESCAPE study assessed whether patients who presented within 12 hours of onset of symptoms would benefit from mechanical thrombectomy [62]. The patients included in the study had a proximal vessel occlusion in the anterior circulation and they all received intravenous tPA [62]. The experimental group also received mechanical thrombectomy [62]. The results of the study showed that patients who received mechanical thrombectomy had substantial increase of functional independence (53% in the treatment group versus 29.3% in the control group; P < 0.001), decreased mortality in the intervention group and similar intracerebral hemorrhage rates [62].

The REVASCAT study examined whether there is a difference in outcome in patients when treated with a combination therapy of both intravenous tPA (if eligible) and mechanical thrombectomy than those treated with medical therapy alone [63]. The patients who were included in the study had to present within 8 hours of onset of symptoms and had to have a proximal anterior circulation occlusion [63]. Solitaire stent retriever was the device used for the thrombectomy group [63]. The results of the study showed that functional independence was increased in the experimental group, with 43.7% having functional independence (mRS score of 0–2) in 90 days versus 28.2% in the control group [63]. The rates of intracerebral hemorrhage remained the same in both groups [63].

The SWIFT PRIME study aimed to determine whether patients treated with both intravenous tPA and Solitaire Revascularization Device within 6 hours of

symptoms onset had better outcome than those who were treated with intravenous tPA alone [64]. The results of the study showed that there was a greater proportion of patients in the experimental group that were functional independent at 90 days in comparison to the control group [64]. Secondary outcomes such as functional independence at 90 days, improvement in NIHSS score and successful reperfusion at 27 hours were better in the treatment group versus the control group [64]. There was no significant difference in complications between the two groups [64].

The EXTEND IA study aimed to determine whether patients treated with both intravenous tPA and Solitaire Revascularization Device within 4.5 hours of symptom onset had better outcome than those who were treated with intravenous tPA alone [65]. The results of the study showed that reperfusion at 24 hours was better in the experimental group versus the control group (median, 100% vs. 37%, P < 0.001) [65]. The neurological improvement at 3 days and the functional outcome was better in the experimental group versus the control group [65]. With regards to adverse consequences such as death and intracerebral hemorrhage the results were similar between the two groups [65].

Subsequently, a meta-analysis published in 2016 looked at the results from the above five randomized controlled trials [60]. There were 1287 patients that were included in the study and who had an acute proximal anterior circulation stroke [60]. Prior to randomization to the two groups patients received intravenous tPA if they met the inclusion criteria [60]. The major results of this meta-analysis were: 1) endovascular thrombectomy led to reduced disability at 90 days, 2) the risk of intracerebral hemorrhage and symptomatic hemorrhage did not differ between the groups and 3) the mortality rate was similar between groups [60].

In 2018, two major randomized controlled studies the DAWN and the DEFUSE 3 were published [66, 67]. The data collected from these studies showed that mechanical thrombectomy can be extended to 24 hours from onset of stroke symptoms [66, 67]. The DAWN study randomized patients to receive either intravenous tPA alone (control group) or thrombectomy plus intravenous tPA (experimental group) [66]. The patients had an intracranial internal carotid artery or proximal middle cerebral artery occlusion and were last known well 6–24 hours prior [66]. The patients included in the study had disproportionately worse neurological exam in comparison to the infarct volume that was observed on imaging [66]. The study showed that at 90 days the thrombectomy group had a better mRS score and improved functional independence [66]. Adverse effects such as intracerebral hemorrhage and death were similar between the two groups [66].

The DEFUSE 3 study was a multicenter, randomized, open-label trial, in which the control group received intravenous tPA and the experimental group received endovascular therapy plus intravenous tPA [67]. Patients who were included in the study had onset of symptoms 6–16 hours prior to presentation, were found to have proximal middle cerebral artery or internal carotid artery occlusion with initial infarct size less than 70 ml and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 [67]. The study showed that patients who underwent mechanical thrombectomy had an increase chance of being functionally independent (45% vs. 17%, P < 0.001) and the 90-day mortality rate was 14% in the experimental group versus 26% in the control group [67]. Symptomatic intracerebral hemorrhage and adverse effects were similar between the groups [67].

It is worth mentioning that acute ischemic stroke can be managed by artery stenting. The Stent-Assisted Recanalization in Acute Ischemic Stroke (SARIS) trial was a prospective trial the goal of which was to determine whether cerebral arterial stenting would be beneficial in the management of acute ischemic stroke [68]. In a series of twenty patients the mRS score of 3 was achieved in 60% and that of 1 was achieved in 45% [68]. Symptomatic intracerebral hemorrhage was present in 5% of the patients

and asymptomatic intracerebral hemorrhage was present in 10% [68]. There is, however, no consensus on whether the benefits of arterial stenting in acute stroke outweigh the risks primarily due to the lack of randomized controlled trials [69].
