Professor Liu Ming: Five difficult problems in the clinical diagnosis and treatment of acute stroke and their solutions!

*For medical professionals to read and refer to the NCN 2021 exciting content express, don’t miss the 24th National Neurology Conference of the Chinese Medical Association in September 2021, Professor Liu Ming from West China Hospital of Sichuan University, for us Put forward the main difficulties and related problems in the clinical diagnosis and treatment of acute stroke, and bring us corresponding solutions and countermeasures.
Next, let's learn together! 1.
In clinical research, most of the results of randomized controlled trials (RCT) in the treatment of stroke with the main goal of reducing death/disability rate are negative ▌ [Current problems] 1.
Research on the treatment of acute stroke The current internationally recognized main efficacy indicators in China are mostly used to reduce the death or disability rate at three months after the onset of disease [measured by the modified Rankin scale (mRs)], or to reduce the mortality rate at three months, Liu Ming The professor pointed out, would such an indicator be more simple and rude? 2.
Except for thrombolysis and thrombectomy RCT tests, which have positive results, most other treatment studies have negative results.
The possible reasons are: the treatment method itself is not effective; the disease itself is difficult to cure; the research design and implementation problems have caused False negative results? ▌ [How to make improvements? 1], the treatment goal in addition to reducing the rate of death or disability, but also whether to set other goals worthy of discussion, such as improvement in signs and symptoms score [National Institutes of Health Stroke Scale (NIHSS)], improved quality of life and so on
.

However, these goals have not been universally recognized internationally due to limited clinical significance or subjectivity of the measurement
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At present, there are four levels of internationally judged efficacy indicators: ① Pathophysiology (such as laboratory and imaging indicators); ② Diseases (symptoms and signs scales, such as NIHSS scale); ③ Living ability [ADL (ADL) assessment Scale and mRs are currently the most commonly used main outcome indicators or endpoint indicators]; ④Quality of life (quality of life), these indicators have their own advantages and disadvantages; then how to choose the efficacy indicators? Professor Liu Ming recommends: long-term endpoint indicators (for example, death and disability) for confirmatory trials; intermediate indicators (for example, symptom and sign scale) for exploratory research
.

2.
The research of Professor Liu Ming’s team "Aims of Treatment of Acute Stroke: A Survey of Chinese Medical Staff’s Viewpoints" is mainly aimed at understanding Chinese medical staff’s opinions on the selection of curative effects in the acute phase of stroke through a questionnaire survey.
The results show that: ①Reduce deaths It is the most important curative effect index for Chinese medical staff; ②When death or disability cannot be reduced, quality of life is an acceptable outcome index, and neuroprotection and traditional Chinese medicine are the most commonly selected treatments; ③Compared to other outcome indicators, Chinese medical staff is right The weight of hemorrhage conversion is lower than expected
.

2.
Large-area, severe and critically ill cerebral infarction is the most important type of death/disability, but there are great difficulties in treatment ▌ [Current problems] Severe, large-area, and critically ill cerebral infarction is death and disability The main type of treatment is often poor
.

There is evidence that invasive decompressive craniectomy can reduce the death and disability rate, but the clinical use rate is still very low; non-invasive suitable therapies (using dehydrating agents, hormones, etc.
) are convenient to use, but there is a lack of RCT evidence; therefore There are still great difficulties in treatment
.

▌ [How to make improvements? 】 1.
The treatment is difficult, so it is a scientific and feasible strategy to pay attention to prevention; at the same time, it is reasonable to classify and take preventive measures in stages
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In terms of treatment: in addition to intensive care treatment, the occurrence of critical illness should be prevented from the very early onset; in terms of prevention: attention should be paid to the special risk factors of large-scale and critically ill cerebral infarction (such as heart disease) from primary prevention and adolescence.
And prevention of atrial fibrillation and aortic atherosclerosis
.

2.
It is necessary to clarify related concepts and types, and adopt more targeted prevention and control measures
.

At present, the relevant concepts at home and abroad are fuzzy, and the terms and definitions are not uniform; therefore, Professor Liu Ming’s team sorted out the relevant concepts and summarized four important clinically practical and operable concepts: ①Large-area cerebral infarction: based on imaging Performance, cerebral hemisphere infarction: CT plain scan-within 6 hours of onset, plain CT shows the infarct area> 1/3 of the middle cerebral artery blood supply area, or 6 hours to 7 days after the onset, CT plain scan shows the infarct area> 1/2 of the brain Middle artery blood supply area; MRI-within 6 hours of onset, MR-DWI shows infarct volume> 80ml or within 14 hours of onset of infarct volume> 145ml; cerebellar infarction: imaging infarct diameter> 3cm
.

②Severe cerebral infarction: Based on the definition of clinical manifestations, the total score of NIHSS score ≥ 15 points or the NIHSS score of dominant hemisphere cerebral infarction ≥ 20 points, non-dominant hemisphere infarction ≥ 15; Glasgow coma score (GCS): cerebral hemisphere ≤ 8 points, Cerebellar infarction is less than or equal to 9 points
.

③Malignant cerebral edema: based on clinical + imaging manifestations, large area + severe, it is a critical condition; definition: large area cerebral infarction cerebral edema progressively worsens, disturbance of consciousness and pupils are not equal, the image shows midline shift or brainstem Compression can lead to brain herniation, death or severe disability
.

④ Critical cerebral infarction: including two types with and without malignant cerebral edema, definition: cerebral infarction patients have one of the following conditions, (1) malignant cerebral edema (impaired consciousness, pupil changes, and brain tissue shift shown by imaging); (2) Respiratory failure requires mechanical ventilation; (3) Shock occurs; (4) Other system organ failure occurs; (5) Surgical intervention or ICU monitoring is required
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Malignant cerebral edema is critically ill, and critically ill cerebral infarction is not necessarily accompanied by malignant cerebral edema, and the focus of prevention and treatment is different
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3.
Severe/large-area cerebral infarction diagnosis and evaluation process (see Figure 1)
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Figure 1: Severe/large-area cerebral infarction diagnosis and evaluation process III.
Hemorrhage transformation after acute cerebral infarction: is the main reason for the low use rate of reperfusion therapy.
The efficacy of thrombolysis and thrombectomy is supported by evidence but the use rate is still not ideal; dual antiplatelet A larger range of appropriate use and duration of treatment are to be studied; it is difficult to measure the benefits of individual patients and the pros and cons of bleeding side effects; research on the correlation between bleeding transformation and outcome and the identification of high-risk individuals will help more accurate patients with cerebral infarction Individualized treatment; more accurate start-up time of antiplatelet and anticoagulation for patients with cerebral infarction hemorrhage transformation needs further study
.

4.
What are the key issues of feasible strategies for individualized prevention and treatment of acute cerebral small vessel disease? It is necessary to clarify the thinking and clarify the easily confused concept of cerebral small vessel disease.
Research work needs to be more closely integrated with clinical problems and feasible prevention and treatment strategies; 1.
The concept of acute cerebral small vessel disease: Cerebral small vessel disease with acute clinical events , It belongs to both cerebral small blood vessels and a special type of stroke
.

Divided into two types: ischemic and hemorrhagic: 1) Commonly used terms of acute ischemic cerebral small vessel disease (belonging to cerebral infarction) (overlapping each other): arteriolar occlusive cerebral infarction (from the perspective of the size of the diseased blood vessel); luminal infarction (From the perspective of infarct size, 3-20mm); new subcortical small infarcts (from the perspective of infarct location); micro-infarcts (from the perspective of infarct size, <5mm); perforator atherosclerotic disease (BAD); 2) Acute hemorrhagic cerebrovascular disease (accounting for the vast majority of primary cerebral hemorrhage): cerebral hemorrhage related to hypertension; cerebral hemorrhage related to amyloid cerebrovascular disease
.

2.
Thinking of individualized treatment of acute cerebral small vessel disease: the general principles are consistent with the corresponding stroke guidelines
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However, with the help of new imaging technologies such as high-resolution magnetic resonance, it has become possible to identify the pathological mechanisms of cerebral arterioles (arterior arteriosclerosis or arteriolar atherosclerosis) in vivo (previously only through autopsy)
.

Therefore, it is expected to become a reality to choose an individualized treatment plan based on the pathological mechanism of cerebral small vessel disease.
For example: 1) Acute ischemic cerebral small vessel disease (luminal infarction, etc.
): ① Simple arteriole sclerosis (hyalinosis): lower blood pressure should be more Positive, and thrombolysis, long-term enhanced statin, long-term dual antiplatelet and other bleeding therapies should be cautious; ②Atherosclerosis: choose thrombolysis, long-term enhanced statin, longer-term double antiplatelet; ③Arterial embolism: thrombolysis , Long-term intensified statin, longer-term double anti-platelet; ④ Cardiogenic embolism: thrombolysis, anticoagulation; 2) Acute hemorrhagic cerebral small vessel disease: ① Arteriole sclerosis (vitrification): hypertension-related cerebral hemorrhage should be active Lower blood pressure; ②Amyloidosis: Patients with cerebral infarction with a history of cerebral hemorrhage or microhemorrhage related to amyloid angiopathy should be cautious when they need thrombolysis, anticoagulation or double antiplatelet because of the increased risk of bleeding
.

5.
The appropriate treatment method for patients with imaging ischemic infarction (stationary cerebral infarction) without typical stroke symptoms is still unclear.
It was found after head imaging on physical examination) if there are no vascular risk factors, should I take statins and antiplatelet drugs for a long time? Professor Liu Ming gave relevant suggestions: 1) Diagnosis: It is necessary to reach a consensus with imaging experts to provide guidance to avoid over-diagnosis or under-diagnosis
.

As far as possible to determine whether it is an acute infarct focus? If it is not an acute infarction, how can it be distinguished from other causes of abnormal white matter signals? 2) Treatment: If it is an acute infarction, the treatment should be the same as that of a typical cerebral infarction; if it is not an acute focus, the long-term use of antiplatelet and statins needs to develop guidelines or consensus to provide guidance; 3) Conduct research: provide for clinical treatment Evidence
.

Summary 1.
To reduce death or disability as the main goal: large area, severe, and critically ill are the key; 2.
Large area, severe, and critically ill cerebral infarction need to be classified and treated in stages; 3.
Hemorrhage transformation after acute cerebral infarction: treatment The balance between effects and side effects needs to be studied; 4.
The key to individualized prevention and treatment of acute cerebral small vessel disease: According to its pathological mechanism, it needs to be further studied; 5.
Patients with imaging ischemic infarction without typical stroke symptoms (without vascular risk factors) ) Clinical treatment: diagnosis-need to reach a consensus with imaging experts to avoid excessive or insufficient; treatment-long-term use of antiplatelets and statins need to develop guidelines or consensus; conduct research-provide evidence
.

 Expert Profile: Professor Liu Ming, Professor, Doctoral Supervisor, and Subject Director of the Department of Neurology, West China Hospital of Sichuan University; Director of the Cerebrovascular Disease Center of West China Hospital; Former member of the Standing Committee of the Chinese Medical Association Neurology Branch and leader of the cerebrovascular disease group, Sichuan Medical Association Neurology Specialty Committee Vice Chairman of the Association and Head of the Cerebrovascular Diseases Group, Chairman of the Evidence-Based Medicine Committee, served as the editorial board of 5 SCI journals including Lancet Neurology, and published many papers, including JAMA, The Lancet Neurology, Chinese Journal of Neurology, etc.
Well-known journals; presided over the key international projects of the National Natural Science Foundation of China, the key special projects of the Ministry of Science and Technology, the Ministry of Education, the Ministry of Health, and many provincial-level projects; successively won a number of ministerial and provincial awards (including the first prize of Natural Science of the Ministry of Education, the first 1.
Completor) Editor-in-chief of 4 textbooks or monographs including the postgraduate planning textbook "Neurosurgery" won the titles of Provincial Academic Technology Leader, Provincial Chief Expert of Health and Family Planning, and Outstanding Contribution of the Ministry of Health.
Note: The content of this article is compiled from the Chinese Medical Association.
Professor Liu Ming's lecture at the 24th National Neurology Conference-"Thoughts on Difficulties in Diagnosis and Treatment of Acute Stroke"
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