New progress has been made in the treatment of acute ischemic stroke. Direct mechanical thrombectomy is expected to improve the treatment rate of patients

Acute Ischemic Stroke (AIS) is the first cause of death and disability in adults in ChinaIt has the characteristics of high incidence rate, high disability rate, high mortality rate and high recurrence rateEvery six seconds, one person in the world dies of strokeIncidence rate and incidence rate of stroke in Europe and America have been decreasing graduallyThe incidence of disease in China has been increasing gradually at 8.7% per year, which is significantly higher than the overall incidence rate of world stroke< br / > < br / > it is not too much to describe the treatment of AIS by "competing against time"If AIS is not treated in time, each patient will lose 2.03 million neurons per minute on averageAfter stroke symptoms appear, choosing the most appropriate treatment means in the best "time window" (0-4.5 hours) combined with the condition can save the life of patients and improve the clinical prognosis< br / > < br / > although there are many methods to treat AIS in clinic, there are only four kinds of effective therapies confirmed by evidence-based medicine: stroke unit, super early thrombolysis, antiplatelet therapy and early regular rehabilitationIn 2019, the guidelines for early treatment of acute ischemic stroke in 2019 issued by the American Heart / Stroke Society and the guidelines for diagnosis and treatment of acute ischemic stroke in 2018 issued by the cerebrovascular group of Neurology branch of Chinese Medical Association, both of which will recombine tissue-type plasminogen activator, RT PA) intravenous thrombolysis is recommended as the first choice for the early recovery of blood flow and improvement of cerebral perfusion in AISHowever, the application of RT PA is limited because of its narrow window, many contraindications and low recanalization rate in the occlusion of large vessels< br / > < br / > in recent years, the early revascularization treatment of AIS has become a hot spot in clinical application and research, including mechanical thrombectomy, thrombolysis, angioplasty and stent implantation, among which mechanical thrombectomy (MT) is the priority of the latest guidelines< br / >In 1996, the U.SFDA approved iv-rtpa as a treatment plan for patients with AIS symptoms and within 3 hours of onsetSubsequently, the 2008 ecass-iii study showed that iv-rtpa was superior to placebo in patients treated within 3-4.5 hours of symptom onsetThe American Heart Association (AHA) stroke guidelines recommend that eligible patients use iv-rtpa within 4.5 hours of symptom onsetEven in this time window, the therapeutic effect of IV rtPA is time-dependentTherefore, all major guidelines suggest that iv-rtpa treatment should be started within 60 minutes after arriving at the hospital, preferably within 45 minutes, so as to save part of brain tissue that has not been necrotized< br / > < br / > 3Large-scale surgery in the past 2 weeks; < br / > < br / > 4Gastrointestinal or urinary system bleeding in the past 3 weeks; < br / > < br / > 5Active visceral bleeding; < br / > < br / > 6Aortic arch dissection; < br / > < br / > 7Artery puncture in the area not easy to compress and stop bleeding in the past 1 week; < br / > < br / > 8Blood pressure rise: systolic pressure ≥ 180 mmHg, Or diastolic blood pressure ≥ 100 mmHg; < br / > < br / > 9Acute bleeding tendency, including blood meal count less than 100 x109 / L or other conditions; < br / > < br / > 10Treatment with low molecular weight heparin within 24 hours; < br / > < br / > 11Oral anticoagulant and INR > 1.7 or PT > 15 s; < br / > < br / > 12Use thrombin inhibitor or XA factor inhibitor within 48 hours, or various laboratory abnormalities (such as APTT, INR, Platelet count, ect, TT or XA factor activity measurement, etc.); < br / > < br / > 13Blood glucose < 2.8 mmol / L or > 22.22 mmol / L; < br / > < br / > 14CT or MRI of the head suggests large area infarction (infarction area > 1 / 3 of middle cerebral artery blood supply area); < br / > < br / > related research and limitations of IV rtPA < br / > < br / > expanding treatment time window can increase IV rtPA indications and benefit more patients In the wake up stroke test, patients with unknown stroke onset time were selected as subjects Based on the mismatch of DWI and flair, iv-rtpa treatment could bring better clinical functional outcome (MRS 0-1) at 90 days At the same time, there was no significant difference in mortality and the incidence of symptomatic intracranial hemorrhage (Sich) between IV rtPA group and control group In the study of < br / > < br / > extend, patients with stroke in 4.5-9h time window or wake-up period were recruited, CT or MRI perfusion imaging was used, image was processed by rapid platform, the size of infarct core and penumbra was measured, and patients with hypoperfusion but still can be rescued (i.e in ischemic penumbra) were screened for RT PA intravenous thrombolysis The results showed that patients with ischemic penumbra were more likely to get good prognosis after iv-rtpa treatment within 4.5-9 hours TNK is a multipoint variant of RT PA Compared with RT PA, TNK has longer half-life and higher fibrin specificity The single intravenous injection of teneplase is simpler than that of ateplase Nor-test phase III clinical study (teneplase vs ateplase in the treatment of ischemic stroke trial) showed that the safety and effectiveness of the two were similar < br / > < br / > in addition, the study of extend-ia-tnk (teneplase vs ateplase before intravascular treatment of ischemic stroke) shows that the reperfusion rate of teneplase group before intravascular treatment is high, and its function recovers well < br / > < br / > the application of IV rtPA is limited due to the narrow treatment window, many contraindications and the low recanalization rate of the artery when the large vessels are occluded Large vessel occlusion (LVO) stroke accounts for 1 / 4 of AIS Because the large thrombus has no response to enzyme digestion, the treatment of iv-rtpa is limited, resulting in a low recanalization rate, only 13% - 50% A meta-analysis of Hermes showed that mechanical thrombectomy reduced the disability of anterior circulation stroke caused by LVO, and most patients benefited regardless of age or region < br / > This guideline supports the combination of IV rtPA and mechanical thrombectomy (MT) for AIS with onset time ≥ 6 h, angiographically confirmed as LVO, age > 18, NIHSS score > 6, and expectations > 6 A meta-analysis of three randomized trials showed that each hour delay in reperfusion resulted in a reduction in disability and functional independence Therefore, within the first six hours, the benefits of MT are also time-dependent < br / > However, there are significant differences in the rate of progression of ischemic penumbra to infarct core and irreversible injury among individuals, which depends on patients' collateral circulation compensation and metabolic needs About 55% of patients with acute large vessel occlusive stroke are slow-moving Even if they exceed the traditional 6-hour time window, they may still benefit from mechanical thrombectomy Inspired by the study of defuse-2, dawn and defuse-3 began to identify patients with slow progress through mismatch between infarct core and perfusion defect imaging, so as to screen late window patients with ischemic penumbra and evaluate the possibility of mechanical thrombectomy < br / > < br / > < br / > Figure 3 CT perfusion defect mismatch The purple area is the infarct core (volume 5ml), and the green area is the low perfusion area (volume 155ml) The ratio of green / Purple area = 31.0; the ratio of green minus purple area = 150ml, and the volume of ischemic penumbra was 150ml < br / > < br / > dawn was designed as a multicenter, prospective, randomized, open label study The end point was evaluated by blind method The patients were included in the study before 6-24 hours Rapid post-processing platform was used to quantify the volume of infarct core and penumbra, and the possibility of trevo stent mechanical thrombectomy to improve the clinical outcome was evaluated In the pre-set interim analysis, the thrombectomy group showed significant advantages over the control group and terminated earlier Finally, 206 patients were included, 107 and 99 patients were randomly assigned to mechanical thrombectomy group and control group The results showed that in terms of efficacy outcome, the ratio of mrs0-2 in mechanical thrombectomy group was significantly higher than that in the control group (49% and 13%) For the safety outcome, there was no significant difference between the two groups in the rate of symptomatic bleeding and 90 day mortality The study of < br / > < br / > defuse-3 is another test of prolonging time window By using CT perfusion or MR diffusion / perfusion imaging method, the late window patients with half dark band and circulatory occlusion 6-16 hours before the onset of the disease were screened to evaluate whether mechanical thrombectomy is better than standard medical treatment The results showed that the 90 day independent ratio (MRS 0-2) of mechanical thrombectomy group was 45%, which was significantly better than that of the control group (17%) It is suggested that mechanical thrombectomy is significantly related to the benefit of functional outcome at 90 days, which can improve the disability of patients < br / > < br / > the launch of dawn and defuse-3 directly rewrites the AIS guidelines of the United States, Canada, Europe and other countries in the world According to the 2018 AHA / ASA guidelines for early management of patients with acute ischemic stroke, the screening of patients with late window thrombectomy should follow the inclusion criteria of dawn and defuse-3 study, and the benefit of mechanical thrombectomy is better than that of the control group, which is a high-level evidence (i-level recommendation, A-level evidence) < br / > < br / > the development trend of MT in the future < br / > < br / > because the recanalization rate of intravenous RT PA thrombolysis is very low in patients with large vessel occlusive stroke, and the recanalization rate of mechanical thrombectomy is high, so the current guidelines more recommend the mechanical thrombectomy of intravenous RT PA bridging But can we skip intravenous thrombolysis and perform mechanical thrombectomy directly? In order to solve this problem, several international collaborative studies are under way, such as swift-direct and mr-clean-no-iv, whose purpose is to evaluate whether direct mechanical thrombectomy is equivalent to or superior to rt-PA in addition to skipping the intravenous thrombolysis bridge and direct thrombectomy, the future hot spots of mechanical thrombectomy are light stroke, mechanical thrombectomy of the core of large infarction and mechanical thrombectomy of the posterior circulation In light stroke, the baseline NIHSS score is less than 6, whether thrombus should be removed, whether patients can benefit from thrombus removal, or increase the risk of additional opening To answer this question, the results of large-scale clinical trials such as in-extremis-moste, endolow and tempo-2 are still needed Patients with large infarct core were defined as those with the effects of baseline CT or DWI, with the scores of patients with aspects < 6, infarct volume ≥ 70ml, or infarct volume > 1 / 3mca blood supply area Should thrombus be removed and opened? Will it increase the risk of ischemia-reperfusion injury and bleeding after opening? In order to solve this problem, the international research results such as Tesla, extremis-last, selec2 and tension are needed The Chinese scholars pay more attention to whether it is better than the control group With the results of best and basilar research, we