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*For reference only for medical professionals, read to expand your horizons and look back at the big picture! At the beginning of 2022, let us review the important research progress in the field of stroke in 2021! To this end, the "Medical Neurology Channel" specially invited Professor Dong Qiang from Huashan Hospital Affiliated to Fudan University to take stock of the important research progress of stroke in 2021
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 Summary of this article: The content is shown in the following table, which runs through the first aid process, acute treatment, secondary prevention and rehabilitation of stroke
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01 Mobile stroke unit improves functional outcomes The mobile stroke unit mentioned here has three characteristics: ① Equipped with mobile CT; ② It has the ability to detect key laboratory indicators; ③ Emergency personnel can perform thrombolysis on patients with thrombolysis indications
.

 This concept makes prehospital thrombolysis possible
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 ▌ B-PROUD study A prospective, non-randomized, controlled, blinded evaluation endpoint intervention study published in JAMA, the primary clinical endpoint is mRS score at 3 months, screening more than 3000 patients, using mobile stroke units respectively and non-mobile stroke units to observe differences in clinical outcomes
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 RESULTS: Patients using mobile stroke units had lower mRS scores at 3 months (acOR 0.
71, 95%Cl 0.
58-0.
86, p<0.
001) and higher rates of intravenous thrombolysis than patients using traditional ambulances (60.
2% vs.
48.
1%), and shorter median time from onset to thrombolysis (50 min vs.
70 min)
.

 In other words, a change in emergency care, such as a mobile stroke unit, can improve the clinical outcomes of patients
.

 ▌ BEST-MSU study A prospective, multicenter, phase III, cluster design controlled study published in NEJM, the primary efficacy endpoint was the 3-month utility-weighted mRS score
.

 The same study found that mobile stroke unit use was associated with better functional outcomes at 90 days (3-month utility-weighted mRS score: 0.
72 vs.
0.
66, mRS 0-1 ratio: 55% vs.
44%, acOR 2.
43, 95 %CI, 1.
75~3.
36, p<0.
001)
.

 In addition, mobile stroke unit significantly shortened the time from last normal to thrombolysis (72 min vs.
108 min, p<0.
001), and also significantly shortened the time from first aid to thrombolysis (46 min vs.
78 min, p<0.
001)
.

 The prehospital model of the mobile stroke unit resulted in significantly better patient outcomes compared to the traditional medical model
.

 02 Direct transport to the cath lab improves functional outcomes▌ ANGIOCAT study A single-center, randomized, controlled, blinded outcome-assessing clinical study published in JAMA Neurol, the primary efficacy endpoint was shift analysis of 90-day mRS score (improvement of 1 point or more probabilities)
.

 The study included 466 patients, and after screening, 174 patients were randomized (89 patients were transported directly to the cath lab and 85 patients were treated by conventional means)
.

 Results showed that direct transport to the cath lab significantly improved patient outcomes (1 point decrease in mRS at 3 months; OR 2.
2, p=0.
009)
.

 In addition, the time from hospital to puncture (18 min vs.
42 min, p<0.
001) and the time from hospital to reperfusion (57 min vs.
84 min, p<0.
001) were also significantly shortened
.

 Therefore, not only changes in prehospital emergency care patterns can improve clinical outcomes, but also changes in in-hospital endovascular treatment procedures can lead to better clinical outcomes
.

 03 Tissue window screening for patients with large vessel occlusion more than 6 hours to strengthen evidence-based ▌ AURORA pooled analysis DAWN study and DEFUSE 3 study both showed the effectiveness of tissue window screening for patients with onset of more than 6 hours of endovascular therapy
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 A study published in The Lancet, the AURORA pooled analysis, meta-analyzed clinical studies of endovascularly treated patients with onset more than 6 hours
.

At baseline, the main prognostic data in the endovascular treatment group and the control group were balanced.
The patients were all about 68 years old, the mean NIHSS score was 16, the median ASPECT score was 8, and the time from onset to randomization.
Both are about 600min
.

 The results of the study showed: ① the endovascular treatment group had better 90-day functional outcomes (acOR 2.
54, p<0.
0001); ② the endovascular treatment group had a higher proportion of patients with a 90-day mRS score of 0-2 (45.
9% vs.
19.
3%).
, p<0.
0001), more patients had early neurological recovery (40.
5% vs.
14.
1%, p<0.
0001); ③ Both groups had symptomatic intracranial hemorrhage (5.
3% vs.
3.
3%) and died within 90 days (16.
5%) % vs.
19.
3%) event rates were not significantly different
.

Subgroup analysis showed that the efficacy of endovascular treatment group (acOR 5.
86, 95%CI 3.
14-10.
94) was significantly better than that of 6-12h group (acOR 1.
76, 95%CI 1.
18-2.
62), except that the time from onset to randomization was 12-24h.
, and there was no heterogeneity of efficacy among subgroups (age, gender, NIHSS score, etc.
)
.

 In conclusion, the AURORA pooled analysis shows that screening suitable patients with anterior circulation large vessel occlusion more than 6 hours after onset by standard imaging methods can still benefit from endovascular therapy.

.

 04 Whether direct thrombectomy is non-inferior to bridging thrombectomy: the conclusion is unclear▌ DEVT study A multicenter, randomized, controlled, non-inferiority clinical study published in JAMA, the primary efficacy endpoint is 90-day mRS 0-2 percentage of points
.

 The study randomized 235 patients out of 509 patients and was terminated early due to reaching a noninferiority margin (mRS 0-2: -10%)
.

 The results showed that the 90-day functional independence rate in the direct thrombectomy group was significantly higher than that in the bridging thrombectomy group (54.
3% vs.
46.
6%; difference 7.
7%, one-sided 97.
5%CI -5.
1%~∞, non-inferiority p=0.
003) There was no significant difference in symptomatic intracranial hemorrhage and 90-day mortality between the two groups
.

 ▌ The SKIP study is also a multicenter, randomized, controlled, non-inferiority clinical study published in JAMA.
The primary efficacy endpoint is good prognosis at 90 days (90-day mRS score is 0-2)
.

 A total of 204 patients were included, and the results showed that there was no significant difference between the direct thrombectomy group and the bridging thrombectomy group in the proportion of patients who achieved a 90-day mRS score of 0-2 (59.
4% vs.
57.
3%; difference 2.
1%, p=0.
18 for non-inferiority).
), failed to demonstrate the non-inferiority of direct thrombectomy
.

 So, one trial is biased to achieve non-inferiority, and the other trial is biased to have no evidence of non-inferiority, and may need more refined patient screening methods for research
.

 ▌ MR CLEAN-NO IV study This is a multicenter, randomized, controlled, superiority design clinical study published in NEJM.
The primary efficacy endpoint is the 90-day mRS score
.

 After randomization of 547 patients, there was no significant difference in the 90-day mRS score between the direct thrombectomy group and the bridging thrombectomy group (acOR 0.
88, 95%CI 0.
65-1.
19).
Its noninferiority margin (acOR 0.
8); safety outcomes did not differ significantly between the two groups
.

 All in all, the three studies published in top journals failed to draw a unified conclusion.
Under such circumstances, preliminary judgment and accurate identification of patients who are suitable for direct thrombectomy or bridging thrombectomy deserve further exploration
.

 05 Endovascular treatment of patients with basilar artery occlusion is inconclusive ▌ BASICS study A multicenter, open-label, blinded, randomized controlled study published in NEJM, the primary efficacy endpoint is the ratio of mRS 0-3 points at 90 days
.

 The results showed that the proportion of patients with a 90-day mRS score of 0-3 was 44.
2% in the endovascular treatment group and 37.
7% in the medical treatment group, with no significant difference in the primary endpoint between the two groups (RR 1.
18, 95%CI 0.
92-1.
50, p= 0.
19); there was no significant difference between the two groups in terms of safety endpoints, including symptomatic intracranial hemorrhage and 90-day mortality
.

 06 New Choice of Intravenous Thrombolytic Drugs ▌ FRIDA Study A multicenter, randomized, open-label, non-inferiority clinical study published in Lancet Neurol, the primary efficacy endpoint is the ratio of mRS 0-1 points at 90 days
.

 Results of the study showed that non-immunogenic staphylokinase was non-inferior to alteplase (90-day mRS 0-1 ratio 50% vs.
41%, OR 1.
47, p<0.
0001 for non-inferiority); both groups There were no significant differences in mortality, symptomatic intracranial hemorrhage, and serious adverse events among the populations
.

 07 A new secondary prevention strategy for precise double-antibody ▌ CHANCE-2 study A multi-center, randomized, double-blind, parallel-controlled clinical study published in NEJM is a further study based on the subgroup analysis results of the CHANCE study.
It is also a strong stroke that China has added to the field of neurology in the world
.

 The inclusion criteria were patients with mild stroke (NIHSS≤3) or high-risk TIA (ABCD2 score ≥4) within 24 hours of onset, aged ≥40 years, and carrying CYP2C19 functional allele deletion
.

 The intervention and control settings were as follows: Ticagrelor group: 180 mg of ticagrelor on the first day, 90 mg twice a day on days 2-90 + aspirin for 21 days
.

Clopidogrel group: Clopidogrel 300 mg on the first day, 75 mg once a day on days 2-90 + aspirin for 21 days
.

 The primary efficacy endpoint was the risk of new stroke within 90 days, and the primary safety endpoint was the risk of moderate to severe bleeding within 90 days
.

 The results of the study found that the 90-day stroke recurrence rate in the ticagrelor group was significantly lower than that in the control group (6.
0% vs.
7.
6%; HR 0.
77, 95% CI 0.
64-0.
94, p=0.
008); All bleeding events and minor bleeding events increased (5.
3% vs.
2.
5%; 5.
0% vs.
2.
2%), but there was no significant difference in the risk of severe or moderate bleeding between the two groups (0.
3% vs.
0.
3%, p=0.
66 )
.

 08 Long-term ECG monitoring improves the detection rate of atrial fibrillation, but the clinical benefit is unclear AF detection rates, including subgroup analyses comparing the differences in AF detection rates between LAA and SVD stroke patients
.

 The results showed: ① The detection rate of atrial fibrillation within 12 months in the implantable ECG monitoring group was significantly higher than that in the routine monitoring group (12.
1% vs.
1.
8%; HR 7.
4, 95% Cl 2.
6-21.
3, p<0.
001)
.

②In the implantable ECG monitoring group, there was no significant difference in the detection rate of atrial fibrillation between LAA and SVD strokes (11.
7% vs.
12.
6%, p=0.
74)
.

③ Among the patients with atrial fibrillation detected, a higher proportion of patients in the implantable ECG monitoring group were given oral anticoagulation (7.
4% vs.
1.
2%, p<0.
001), but there was no significant difference in the stroke recurrence rate between the two groups ( 7.
2% vs.
9.
8%, HR 0.
7, 95% CI 0.
4-1.
4, p=0.
30)
.

 ▌ PER DIEM study An investigator-initiated open-label, randomized clinical trial published in JAMA, the primary endpoint is the occurrence of definite or highly probable atrial fibrillation (duration of new-onset atrial fibrillation ≥ 2 within 12 months after randomization) minutes)
.

 The proportion of patients with AF detected by implantable ECG monitoring was significantly higher (15.
3% vs.
4.
7%; difference 10.
7%, 95% CI 4.
0%-17.
3%, p=0.
003)
.

Secondary endpoint analysis showed that the time to first detect atrial fibrillation lasting more than 2 minutes after randomization in the implantable ECG monitoring group was significantly lower than that in the control group (HR3.
36, 95%Cl 1.
44-7.
84; log-rank test, p=0.
002)
.

 ▌ MonDAFIS study A randomized, open-label, parallel-controlled, multicenter study published in Lancet Neurol.
The primary endpoint was the proportion of oral anticoagulants within 12 months after stroke or TIA
.

 At 12 months, there was no significant difference in the proportion of patients using oral anticoagulants in the intervention and control groups (13.
7% vs.
11.
8%, p=0.
13); .
4.
0%, p=0.
024), and there was no significant difference in the composite outcome of cardiovascular events and death between the two groups
.

 In conclusion, although long-term ECG monitoring can effectively improve the detection rate of atrial fibrillation, its clinical benefit is not clear, and it may be more meaningful to explore other factors affecting anticoagulation decision-making in patients with atrial fibrillation
.

 09 Vagus nerve stimulation brings new hope▌ VNS-REHAB study A multi-center, randomized, blinded, sham-controlled clinical trial published in Lancet, the primary endpoint is the Fugl-Meyer-Upper Limb (FMA-UE) score before and after treatment change
.

 The results showed that the mean FMA-UE score increased by 5.
0 points (SD 4.
4 points) in patients who received 6-week vagal nerve stimulation and 2.
4 points (SD 3.
8 points) in the control group, with a difference of 2.
6 points between groups (95%Cl 1.
0-4.
2, p =0.
0014); after 90 days of treatment, there was still a significant difference in FMA-UE scores between the two groups (47% vs.
24%, p=0.
0098)
.

 10 Secondary Prevention of Intracerebral Hemorrhage A review published in Lancet Neurol stated: Patients with spontaneous intracranial hemorrhage are at risk for recurrent intracranial hemorrhage and new ischemic stroke.
major risk factors for the event
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① Patients with lobar hemorrhage have a higher recurrence rate of intracranial hemorrhage, but the risk of ischemic stroke is similar to that of patients with cerebral hemorrhage in other parts
.

②The risk of recurrent intracranial hemorrhage and ischemic vascular events in patients with atrial fibrillation was significantly higher than that in patients without atrial fibrillation
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▌ SoSTART study A prospective, randomized, open-label, assessor-blind, non-inferiority study published in Lancet Neurol, with the primary endpoint of recurrent symptomatic spontaneous intracranial hemorrhage
.

 After a median follow-up of 201 patients of 1.
2 years, 8% of patients in the anticoagulation group had recurrent symptomatic spontaneous intracranial hemorrhage compared with 4% in the non-anticoagulation group (adjusted HR 2.
42, 95% CI 0.
72-8.
09, p=0.
152 ); because the noninferiority margin was adjusted HR 3.
2, the study failed to demonstrate noninferiority of oral anticoagulants in reducing the risk of recurrent intracranial hemorrhage
.

 ▌ APACHE-AF study A multicenter, prospective, randomized, controlled, blinded endpoint clinical trial published in Lancet Neurol, the primary endpoint is non-fatal stroke or vascular death events
.

 The sample size was 101.
After a median follow-up of 1.
9 years, non-fatal stroke or vascular death occurred in 26% of patients in the anticoagulation group (apixaban) and 24% in the non-anticoagulation group, with no significant difference in the primary endpoint.
(Adjusted HR 1.
05, 95% CI 0.
48-2.
31; p=0.
90)
.

 ▌ RESTART long-term follow-up results published in JAMA Neurol, is a prospective, randomized, open-label, blinded endpoint, parallel-controlled trial long-term follow-up results, the primary endpoint is fatal or non-fatal recurrent symptomatic intracranial hemorrhage
.

 After a median follow-up of 2.
0 years in 537 patients, the incidence of the primary endpoint was 4% in the restart antiplatelet group and 9% in the avoidance antiplatelet group, with an adjusted HR of 0.
51 (0.
25-1.
03, p=0.
060), suggesting restart after intracerebral hemorrhage Antiplatelet therapy is safe
.

 Well, the RESTART study extended follow-up, ending November 30, 2020, with a median follow-up of 3.
0 years
.

 The results showed that there was no significant difference in the incidence of the primary endpoint between the restart anti-plate group and the avoid anti-plate group (8.
2% vs.
9.
3%, HR 0.
87, 95% CI 0.
49-1.
55, p=0.
64); restart anti-plate group and avoid anti-plate group.
There was also no significant difference in the incidence of major vascular events between the plate groups (26.
8% vs.
32.
5%, HR 0.
79, 95% CI 0.
58-1.
08, p=0.
14)
.

 In conclusion, it is safe to restart antiplatelet therapy after intracerebral hemorrhage, but its benefit has not been demonstrated
.

 We are very grateful to Professor Dong Qiang for taking us to review the main studies in 2021 that are of great significance to the clinical practice of stroke, and look forward to more meaningful studies being published in 2022
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 This article organizes the "Heart-to-Heart-Leadership - 2021 Annual Review of Neurology" held by the free "Medical Neurology Channel".
The meeting took stock of 8 major disease areas including stroke, Parkinson's disease, epilepsy, and neuroimmunity.
The meeting was successfully concluded today.
, scan the QR code below or click [Read the original text] to watch the playback
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 Speaker Profile Professor Dong Qiang Director, Chief Physician, Doctoral Supervisor, Department of Neurology, Huashan Hospital Affiliated to Fudan University, Deputy Director, National Medical Center for Neurological Diseases (Huashan) Director of the Expert Committee of Shanghai Stroke Prevention and Treatment Service System Deputy Director of Shanghai Stroke Prevention and Treatment Center Deputy Director of the Neurology Branch of the Chinese Medical Association (the 8th) Vice President of the Chinese Stroke Society Shanghai Medical Association Neurology Branch The current chairman of the tenth committee is the chairman of the Shanghai Medical Association Neurology Branch, the executive vice chairman of the Shanghai Stroke Association, and the source of this article: Neurology Channel of the medical community.
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