Is direct thrombectomy effective for large cerebral infarction within 24 hours of onset?

*Only for medical professionals to read and refer to the ISC conference essence content express! Large-area cerebral infarction is an important disease that leads to human death or disability.
It is mostly caused by the occlusion of the distal internal carotid artery or the main middle cerebral artery.
From the perspective of imaging, it is often defined by the size or volume of the infarct
.

Different studies use different imaging observation time points and different imaging changes as the cut-off value, and CT shows that the low-density area > 1/3 or 1/2 of the middle cerebral artery blood supply area within 6 hours of onset or diffusion-weighted imaging (DWI) prompts Infarct volume >80ml is more commonly used, or infarct size exceeds 33% of the middle cerebral artery area or patients with ASPECTS (Alberta Stroke Program Early CTScore) <6
.

 Endovascular therapy is usually strongly recommended for patients with large cerebral infarction and an ASPECTS score ≥6
.

However, an ASPECTS score of <6 implies a large infarct nucleus that does not match the penumbra, and the effect of endovascular therapy is unclear
.

 Recently, the 2022 International Stroke Congress (ISC 2022) was successfully held, and Shinichi Yoshimura from Hyogo Medical University in Japan announced the results of the RESCUE-Japan LIMIT study
.

The results of the study showed that endovascular treatment was superior to conservative drug treatment for patients with an ASPECTS score of 3-5 within 24 hours of onset after strict screening
.

The results were simultaneously published in the New England Journal of Medicine on February 9, 2022
.

Figure 1 Study title RESCUE-Japan LIMIT Study Description This is a multicenter, randomized clinical trial conducted by Japanese researchers, which included 203 patients with baseline ASPECTS 3-5 (scores range from 0 to 10, lower 101 patients were randomly assigned to endovascular therapy and 102 patients were randomly assigned to The medical-care group
.

Additionally, approximately 27% of patients in each group received alteplase
.

 The primary outcome of the study was a modified Rankin Scale (mRS) score of 0 to 3 (0 to 6, with higher scores indicating greater disability) at 90 days
.

Secondary outcomes included a shift in the range of mRS scores towards better outcomes at 90 days and at least an 8-point improvement in NIHSS scores at 48 hours
.

After 90 days, 31% of patients in the endovascular group had a good prognosis (mRS 0-3), compared with 12.
7% in the conservative medical group (RR 2.
43; 95% CI 1.
35-4.
37, P=0.
002)
.

In addition, 31.
0% of patients in the endovascular treatment group had an NIHSS score improvement of at least 8 points at 48h, while only 8.
8% of patients in the medical conservative treatment group had an NIHSS score improvement of at least 8 points at 48h (RR 3.
51; 95% CI, 1.
76 to 7.
00)
.

Figure 2 Distribution of mRS scores at 90 days
.

A score of 0 means no disability, 1 means no clinically significant disability, 2 means mild disability, 3 means moderate disability but able to walk independently, 4 means moderate disability, 5 means severe disability, 6 means death safety, vascular The rate of intracranial hemorrhage within 48 hours was higher in the internal therapy group than in the conservative medical therapy group (58.
0% vs.
31.
4%; RR 1.
85; 95% CI, 1.
33 to 2.
58; P<0.
001), but symptomatic within 48 hours There were no significant differences between the two groups in terms of intracranial hemorrhage or death within 90 days (Figure 3)
.

Figure 3 Experimental results The results of this study showed that patients with massive cerebral infarction who received endovascular treatment had better functional outcomes than conservative medical treatment, although more intracranial hemorrhage, but the difference in symptomatic intracranial hemorrhage was not significant
.

 In 2019, research published in Stroke also showed that in patients with ASPECTS 0-5 who underwent mechanical thrombectomy, successful recanalization was beneficial without increasing the risk of symptomatic intracerebral hemorrhage
.

 The researchers mentioned that this study has several limitations: First, according to the judgment of the neurologist, this study has already screened out patients with large cerebral infarction who may benefit from endovascular therapy before surgery.
patients
.

The main inclusion and exclusion criteria of RESCUE-Japan LIMIT are as follows: Age of acute cerebral infarction ≥18 years old MRS 0-1CTA or MRA before the onset confirmed ICA or M1 segment occlusion CT or DWI showed ASPECTS score 3-5 within 6 hours of onset or onset of 6 - Within 24 hours, but there should be no lesions on FLAIR.
CT or MRI showed no obvious midline shift.
Wu Chuanjie, deputy chief physician of the Department of Neurology, Xuanwu Hospital, Capital Medical University, introduced: "The key points here are that the object is the anterior circulation.
The internal carotid artery or the M1 segment of the middle cerebral artery, if the patient has onset within 6-24 hours, it is required that there should be no lesions on the FLAIR.
This is difficult.
In fact, the mismatch between DWI and FLIAR indicates that the actual onset time of the patient is short, and there is a large ischemia half.
dark band
.

Therefore, in this study, more than 70% of patients had onset within 6 hours, and more than 50% of patients had onset within 4.
5 hours
.

Therefore, he believes that the significance of the RESCUE-Japan LIMIT study is not to say that patients with massive cerebral infarction can have thrombectomy indiscriminately, and it is debatable to use ASPECTS to equate with massive cerebral infarction
.

The greatest value of RESCUE-Japan LIMIT Yes, we cannot clinically rule out patients who should be treated with endovascular therapy on the basis of so-called ASPECTS foci alone
.

 Second, although most guidelines recommend against the use of alteplase in the presence of extensive ischemic changes on imaging (rt -PA ), but a small number of patients still use rt-PA, which may change the results of the two groups and adversely affect the conservative medical treatment group
.

In addition, there are 5 clinical trials for large core infarction underway around the world
.

This research result of Japanese scholars has surprised clinicians
.
In addition
to our joy, we must also be soberly aware of RESCUE-Japan LIMIT There are some subtle differences in the design of the thrombectomy study
.

Although the ASPECTS score was used in the imaging evaluation of RESCUE-Japan LIMIT, it should be noted that the evaluation object is mostly diffusion imaging (DWI) of MRI, not CT.
Non-enhanced imaging
.

DWI is more accurate and sensitive in identifying early ischemia than plain CT
.

This difference may make patients with small core infarction originally assessed by CT into the interventional treatment group
.

Of course, from the side, it also suggests that endovascular interventional therapy under the guidance of emergency MRI is worthy of promotion in China
.

In addition, you can also focus on the primary endpoint of the study, which was an mRS score of 0 to 3 at 90 days, rather than 0 to 1
.

This is a natural design
.

Because the prognosis of large core infarcts is generally poor, the standard setting for prognosis should be lowered
.

You can note that there is no difference in the ratio of 90-day mRS scores of 0 to 1 between the RESCUE-Japan LIMIT groups.
This homeopathic design is also worth learning
from.

Expert Profile Mao Yiting Deputy Chief Physician of the Department of Neurology, Huashan Hospital Affiliated to Fudan University, MD, is mainly engaged in internal medicine and interventional diagnosis and treatment of cerebrovascular diseases, and is a member of the cerebrovascular emergency team of Huashan Hospital
.

Graduated from the seven-year clinical medicine program of Shanghai Medical College of Fudan University
.

He has studied in internationally renowned centers such as the Oxford University Clinical Research Center and the Neurology Department of the Royal Melbourne Hospital in Australia
.

He was once appointed by the Organization Department of the Central Committee to Kashgar, Xinjiang, to support local medical undertakings
.

As the first author or corresponding author, he has published a number of academic papers in the fields of cerebrovascular disease, epilepsy, neuroimmunity, etc.
, with a cumulative impact factor of more than 20 points
.

Presided over a project of the National Natural Science Foundation of China and participated in a project of the Ministry of Science and Technology
.

He is an outstanding charity volunteer in Shanghai, and has been rated as an advanced worker, outstanding party member, trade union activist, and outstanding volunteer of Huashan Hospital for many times
.

Reference source: [1] Yoshimura S, Sakai N, Yamagami H, et al.
Endovascular Therapy for Acute Stroke with a Large Ischemic Region[J].
New England Journal of Medicine, 2022.
DOI: 10.
1056/NEJMoa2118191[2]https: //mp.
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