Can thrombolysis in mild and wake-up strokes?

*Only for medical professionals to read for reference minor symptoms, major hidden dangers! In our clinical work, we often encounter patients with mild strokes and strokes after waking up.
How to treat them with intravenous thrombolysis is a difficult clinical problem
.

At the 7th Annual Conference of the Chinese Stroke Society, Professor He Li from West China Hospital of Sichuan University gave a systematic explanation of "Small Symptoms and Big Hidden Dangers: Multidimensional Thinking of Light Stroke and Venous Thrombolysis Strategies after Wake Up".
This time The explanation includes the concept of light stroke, the harm of light stroke, how to dissolve light stroke intravenously, the concept of stroke after awakening, the related research of stroke after awakening, and the recommendations for intravenous thrombolysis after awakening stroke
.

01 Light stroke ▌ The concept of light stroke was proposed by the article "What is minor stroke" published in Stroke in 2010.
The definition of light stroke is complicated and it points out two types of stroke patients with practical significance: (1) US National Each item of the Institute of Health Stroke Scale (NIHSS) must be 0 or 1, and the consciousness item must be 0; (2) The total baseline NIHSS score is ≤3
.

In 2016, China's "Guidelines for the Diagnosis and Treatment of High-Risk Non-disabling Ischemic Cerebrovascular Events" pointed out that due to the inconsistent standards, according to the results of previous clinical studies, mild stroke can be defined as: NIHSS score ≤ 3 points; NIHSS score ≤ 5 points ; Modified Rankin Scale (mRS) score ≤ 3 points; any of the above
.

▌ The harm of mild stroke It is generally believed that patients with mild stroke have a good prognosis, and the risk of acute reperfusion therapy is significantly greater than the benefit
.

However, the prognosis of these patients is actually not so good.
About one-third of the patients become disabled or die 90 days after the stroke (mRS score is 2-6 points)
.

PS: Mild stroke ≠ good prognosis
.

▌ The guidelines for intravenous thrombolysis for mild stroke are recommended.
At present, there is still controversy regarding intravenous thrombolysis for mild stroke.
Does not thrombolysis affect the prognosis of patients? Does thrombolysis benefit the patient and does it increase the risk of bleeding? Professor He pointed out that studies on intravenous thrombolysis for mild strokes, such as the WSO study and PRISMS study, found that patients did not benefit from intravenous thrombolysis for non-disabling mild strokes
.

WSO study: The Austrian national cohort study included a total of 80,634 stroke patients with a mild initial assessment of stroke severity (NIHSS 0-5 points), based on admission severity (NIHSS 0-1 points and NIHSS 2-5 points) and intravenous Comparing the use of thrombus, it was found that intravenous thrombolysis did not increase the probability of an excellent prognosis in patients with NIHSS scores of 0-1
.

The PRISMS study is a phase 3b, double-blind, double-placebo, multi-center randomized clinical trial.
It included patients with acute ischemic stroke with a NIHSS score of 0-5 and non-obviously disabling from May 30, 2014 to December 20, 2016, in the United States 75 The hospitals were treated with alteplase and aspirin, and it was found that intravenous thrombolysis within 3 hours after the onset of mild non-disabling stroke did not improve the short-term prognosis and had a higher risk of symptomatic intracranial hemorrhage
.

Therefore, for the thrombolytic treatment of mild stroke, the guidelines recommend: Sino-US intravenous thrombolysis scientific statement recommends thrombolytic treatment within 3 hours of disabling and non-disabling mild stroke
.

The 2018 AHA/ASA guidelines also distinguish the treatment of mild stroke according to whether it is disabling
.

2021 "European Stroke Organization (ESO) Acute Ischemic Stroke Intravenous Thrombolysis Guidelines", thinking about non-disabling stroke patients with large vessel occlusion
.

Therefore, in the 2021 European Stroke Organization (ESO) Acute Ischemic Stroke Intravenous Thrombolysis Guideline, it is pointed out that for patients with acute mildly disabling ischemic stroke whose onset time is less than 4.
5h, we recommend intravenous thrombolysis ( Strong recommendation, moderate quality evidence); acute mild non-disabling ischemic stroke patients with onset time <4.
5h, we recommend not intravenous thrombolysis (weak recommendation, moderate quality evidence); acute mild onset time <4.
5h Patients with low-degree non-disabling ischemic stroke and large vessel occlusion has been confirmed, and there is insufficient evidence to make evidence-based recommendations (insufficient evidence)
.

02 Stroke after waking up▌ The concept of stroke after waking up A wake-up stroke (WUS) refers to a patient who has no signs of neurological impairment when he falls asleep, but is found to have stroke symptoms by himself or by witnesses after waking up
.

It accounts for about 1/4 or even more of all acute ischemic strokes (AIS)
.

Because the actual time of stroke symptoms is uncertain, WUS patients are usually not eligible for intravenous thrombolysis and are excluded from most clinical trials
.

▌ Progress in intravenous thrombolysis of stroke after awakening 1) Wake-up study entry criteria: (1) Clinically diagnosed as an ischemic stroke with unknown onset time (stroke after waking up or unknown onset time); (2) Finally, it looked normal Time> 4.
5 hours; (3) There is a clear neurological deficit; (4) 18-80 years old; (5) Treatment can be initiated within 4.
5 hours after the stroke is found; (6) Emergency MRI examinations can be completed, including DWI and FLAIR and MRI showed mismatch in DWI-FLAIR (DWI high signal, FLAIR negative)
.

Results: 503 cases, 254 cases of thrombolysis group, 249 cases of control group were included.
The proportion of patients in the thrombolytic group with a good prognosis (90 days mRS 0～1) was 53.
3%, while that of the control group was 41.
8%; the mortality rate at 90 days ( 4.
1% vs 1.
2%, P=0.
07); Parenchymal hemorrhage type 2 (4.
0% vs 0.
4%, P=0.
03)
.

2) The inclusion criteria for the EXTEND study are as follows: (1) 18 years of age or older; (2) no previous significant disability (mRS <2); (3) NIHSS score 4-26; (4) CTP or MRP shows low perfusion volume/infarction Core volume>1.
2, and absolute difference>10 ml, and infarct core <70 ml (low perfusion area is defined as rCBF decreased by more than 30% compared to the contralateral side, infarct core is defined as Tmax>6s, assessed by RAPID software)
.

Results: The good prognosis rate of patients in the alteplase intravenous thrombolysis group was 35.
4%, and that of the control group was 29.
5%.
After adjustment, there was a statistical difference between the two, P=0.
04; the incidence of symptomatic cerebral hemorrhage in the intravenous thrombolysis group was 6.
2 %, the control group was 0.
9%, the difference was not statistically significant after adjustment, P=0.
053
.

3) Meta-analysis and random-effect meta-analysis, including four large-scale clinical studies of ECASS IV, EXTEND, Michel and WAKE-UP, evaluating the use of advanced imaging technology to screen patients with acute ischemic stroke whose onset time is unknown or more than 4.
5 hours.
The efficacy of thrombolysis
.

Adjusting for confounding factors, intravenous thrombolysis is still associated with a higher 3-month good functional prognosis, functional improvement and symptomatic intracranial hemorrhage (sICH)
.

Research conclusions: For patients with acute ischemic stroke whose onset time is unknown or whose onset time exceeds 4.
5 hours, advanced neuroimaging technology is used to screen patients suitable for intravenous thrombolysis.
Although the risk of sICH is increased, it is still possible to achieve complete recanalization and recanalization.
The function improved at 3 months
.

▌ The guidelines for intravenous thrombolysis after waking stroke suggest that the 2021 European Stroke Organization (ESO) Acute Ischemic Stroke Intravenous Thrombolysis Guide points out: For patients with stroke after waking up, if the last seen normal time is more than 4.
5 hours, MRI DWI-FLAIR does not match, and it is not suitable or planned for mechanical thrombus removal.
Intravenous thrombolysis is recommended (strong recommendation, high-quality evidence); for patients with acute ischemic stroke who have stroke after waking up, if starting from the midpoint of sleep 9 CT or MRI core/perfusion mismatch within hours, and mechanical thrombus removal is not suitable or planned, rt-pa intravenous thrombolysis is recommended (strong recommendation, moderate quality evidence)
.

03 Summary At the end, Professor He summarized the content of the lecture.
For mild stroke: minor symptoms, major hidden dangers, and easy to be ignored
.

In clinical work, we should think from multiple dimensions such as patient symptoms, imaging and vascular conditions, and specify thrombolytic strategies
.

For patients with acute mild disabling ischemic stroke whose onset time is less than 4.
5h, intravenous thrombolysis is unanimously recommended; for patients with acute mild non-disabling ischemic stroke whose onset time is less than 4.
5h, intravenous is recommended not Thrombolysis
.

For stroke patients after waking up, the key to treatment is mainly multimodal imaging evaluation
.

If the last seen normal time is more than 4.
5 hours, and within 9 hours, CT or MRI core/perfusion does not match, and mechanical thrombus removal is not suitable or planned, intravenous thrombolysis is recommended
.