Congress in October 2014 [36]. The eligibility for patients was onset within 6hours, proximal occlusion of the anterior circulation (distal ICA, M1 or M2, rst or second portion of anterior cerebral artery, A1 or A2), and an NIHSS score>2. As a single- country trial conducted in the Netherlands, patients were randomly assigned to either intra-arterial treatment plus usual care or usual care alone.

The uniqueness of this trial stemmed from multiple factors, including the use of baseline vessel imaging (CTA, MRA, or DSA) for the location of the occlusion as an inclusion criteria. Additionally, the vast majority of patients received IVT (89%), and 82% of patients were treated with stent retrievers. Another unique factor was the use of adjusted common odds ratio for a shift in the direction of a better outcome on the mRS rather than a dichotomized mRS as the primary outcome.

The study showed the adjusted common odds ratio was 1.67 (95% CI 1.21–2.30), for patients treated by intra-arterial therapy, representing the rst positive RCT for endovascular therapy. More patients achieved functional independence (mRS 0–2) at 90days in the intervention group, 33% compared to 19% (95% CI

5.9–21.2) with an adjusted odds ratio of 2.16 (95% CI 1.39–3.38), a statistically signicant result.

Unlike the IMS III trial and the SYNTHESIS Expansion trial, MR CLEAN required a radiologically proven intracranial occlu­sion for study eligibility. When the IMS III trial was designed, the availability of CTA was still limited, and the presence of a proxi­mal arterial occlusion was therefore uncertain in a subgroup of patients in that trial (47% of the study population). Thus, a group of patients in which it is likely that intra-arterial treatment would not alter the natural history of acute ischemic stroke was excluded. Moreover, the study beneted from the widespread availability of retrievable stents, which were shown to be superior to the rst­generation MERCI device for both revascularization and clinical outcomes. Given that these were used in 82% of the patients in the intervention group, this served as an attestation for the impact of a new technology which was not previously assessed as the major thrombectomy modality.

The ESCAPE trial [37], conducted from February 2013 to October 2014 across 22 sites in Canada, the USA, Ireland, and South Korea, allowed recruitment of patients within 12hours, the

signied that the blood ow supplying brain tissue varied depend­ing on the vessel route, indicating that a poststroke treatment was possible by salvaging the tissue at risk of infarction.

Baron etal. [42] performed PET within 18hours of onset in a cohort of 30 patients with a rst-ever middle cerebral artery

Despite its efcacy, PET presents with certain limitations, including cost, complexity of the procedure, relatively poor spa­tial resolution, limited access, the long time necessary to produce the tracers with a cyclotron and dedicated hot chemistry due to the short half-lives of the positron emitters, performing the measurements, making the use of PET in acute clinical settings impractical, and rarely clinical use.

In an attempt to transition toward more practical modalities, the interest in MRI for acute stroke was predicated on the devel­opment of diffusion-weighted imaging (DWI). The basis of DWI involves the reduction in ATPase activity that occurs almost immediately after onset of severe ischemia, which then causes a redistribution of water from the extracellular space to the intracel­lular space. This leads to “restricted diffusion” and reduction in the ADC, which correlates with irreversibly damaged tissue.

DEFUSE, an observational study involving 74 patients [54], and EPITHET, a randomized controlled trial [55], used PWI/DWI mismatch to examine the time window for tPA to 6hours. These

studies suggested that tPA improved clinical outcome and sal­vaged the penumbra between 3 and 6 hours of stroke onset. However, the aforementioned trials from the early 2000s suffered from lack of standardization of core and penumbral assessments.

patients treated with IVT were excluded because their CTA did not demonstrate a large artery occlusion. It was estimated that 25% of clinically eligible patients for thrombectomy were excluded on the basis of perfusion imaging alone. All randomized patients received IVT and endovascular treatment commenced within 6 hours. This selective cohort produced excellent out­comes. The reperfusion rate was 86%, and this trial had the largest effect size, with 71% of patients in the intervention group achiev­ing functional independence (mRS 0–2) at 90days, compared to 40% in the control arm (p = 0.01, relative risk, RR 1.8). Furthermore, this trial demonstrated a large trend to mortality benet (20 to 9%), although unlike the ESCAPE trial, the differ­ence was not statistically signicant (RR 0.4, 95% CI 0.1–1.5), probably due to the small sample size.

degree of benet of performing mechanical embolectomy within the established 6-hour window and whether mechanical embolec­tomy past 6 hours was benecial. The HERMES authors con­cluded that earlier endovascular embolectomy, along with medical therapy, was associated with better functional outcome at 90days and that this became nonbenecial after 7.3hours as compared to standard medical therapy alone.

Overall, the four studies were similar in methodology and pre­sented with results that favored IAT.Additionally, they relied on referrals to experienced endovascular centers, required documen­tation of intracranial occlusion, and aimed at recanalization within 6hours using stent retriever technology (82–100% overall). The main difference was that these four studies required documenta­tion of occlusion, had a time window goal of <6hours for recana­lization, and for the most part used stent retrievers that achieved faster and more complete recanalization than previous studies. Interestingly, in a subgroup analysis, the Interventional Management of Stroke III patients with documented occlusion and similar NIHSS ranges who achieved recanalization within 6hours also benetted. The requirement of CTA documentation of occlusion before randomization allowed the investigators in these trials to optimize their ability to detect differences between the two groups. Moreover, the authors assured that in the patients in intervention group all had the disease they were intended to intervene on and that the control group was going to do badly without the intervention.