The first edition of "Chinese Expert Consensus on Clinical Evaluation and Treatment of Acute Cerebral Infarction Ischemic Penumbra" is released!

The ischemic penumbra is the key to the treatment of acute ischemic stroke, and its evaluation and treatment are highly valued by clinicians
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However, the current clinical evaluation methods and criteria for ischemic penumbra are different at home and abroad, and there is no consensus on the treatment
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A few days ago, led by the Neurologist Branch of the Chinese Medical Doctor Association, the cerebrovascular disease group (special committee) organized the first edition of "Chinese Expert Consensus on Clinical Evaluation and Treatment of Acute Cerebral Infarction Ischemic Penumbra" ( (Hereinafter referred to as the consensus) was officially released, and the relevant expert seminar organized by the Chinese Journal of Neurological and Mental Diseases was successfully held at the Nanjing Jinling Hotel on the eve of the 14th Annual Meeting of Neurologists of the Chinese Medical Doctor Association
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Here, we invite Professor Yu Shengyuan, the chairman of the Neurology Branch of the Chinese Medical Doctor Association, the director of the Department of Neurology of the First Medical Center of the Chinese People's Liberation Army General Hospital, and the consensus correspondent author, author and editorial board member of the Chinese Medical Association Neurology Branch designate Chairman, Deputy Dean of the First Affiliated Hospital of Sun Yat-sen University, Director of Neurology, Professor Zeng Jinsheng, Chief Scientist of the National "973" Project, Honorary President of Neurology Branch of Chinese Medical Doctor Association, Professor Xie Peng of the First Affiliated Hospital of Chongqing Medical University, Capital Professor Song Haiqing, Chief Physician of the Department of Neurology of Xuanwu Hospital of Medical University, Professor Wu Bo, Deputy Director of Department of Neurology, West China Hospital of Sichuan University, Vice President of Neurology Branch of Chinese Medical Doctor Association, and Professor Xu Yun, Director of Department of Neurology of Nanjing Gulou Hospital, on the background of writing this consensus, The clinical value and specific content have brought us in-depth interpretation
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Rescuing the ischemic penumbra is the key to clinical treatment, and writing a consensus is of great significance.
Professor Zeng Jinsheng from the perspective of the evolution of the concept of ischemic penumbra and its clinical significance, Professor Zeng Jinsheng believes: ➤From the perspective of the definition of ischemic penumbra It has the following four characteristics: ①The same vascular innervation area as the core of the infarction; ②Nerve cell dysfunction, but not yet dead; ③Prompt improvement of hypoperfusion can return to normal and bring better clinical outcomes; ④Otherwise, it may worsen and progress to Infarct focus and aggravate brain damage
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➤The development and evolution of the concept of ischemic penumbra has allowed us to gradually clarify the existence of this salvable tissue, and brought clinical treatment strategies to prolong the survival time of ischemic penumbra and save ischemic brain tissue
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➤The cascade reaction in the ischemic penumbra is not only similar to the infarct area, but also unique
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The inflammatory response in the ischemic penumbra has two-sidedness.
On the one hand, it causes brain tissue damage, and on the other hand, it plays a role in protecting nerves by promoting collateral branches
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Based on the above-mentioned pathophysiological basis, the ischemic penumbra has become the focus of attention in acute cerebral infarction, as the nerve tissue around the infarction area that still has a chance to save
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Professor Xie Peng talked about the original intention of writing the consensus.
Professor Xie Peng said in an interview that the concept of ischemic penumbra was proposed 20 or 30 years ago.
There are two main reasons why we wrote the consensus at this point in time.
Reason: ➤On the one hand, the research progress on the ischemic penumbra is constantly updated and the evaluation technology is constantly evolving.
We need to enrich the original knowledge and re-understand the clinical value of the ischemic penumbra in order to achieve new treatment goals
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➤On the other hand, the treatment of acute cerebral infarction in the past 30 years has entered a relative dilemma and misunderstanding
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In the acute phase, thrombolysis, thrombectomy, or bridging therapy can be given to patients within the time window, but in clinical practice, less than 3% of patients can eventually receive treatment within the time window, and what about 97% of the patients? With the development of imaging and the concept of tissue window, we have learned that there are individual differences in the ischemic penumbra of different patients.
Some ischemic penumbras still exist in the subacute phase, so even if it is over time window Patients may also have hope of treatment.
Standardizing clinical evaluation and treatment of ischemic penumbra will open up a broader treatment window and bring new treatment concepts to the clinic
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Professor Yu Shengyuan and Professor Yu Shengyuan pointed out in the interview that the release of the consensus has important clinical significance: ➤First, let clinicians pay attention to the importance of the treatment of ischemic penumbra; ➤Second, let everyone understand and grasp the deficiency.
Blood penumbra evaluation method; ➤The third is to provide a reference for clinical treatment decision; ➤The fourth reminds clinicians to treat the ischemic penumbra from various aspects to reduce early neurological deterioration and reduce the mortality and disability of stroke Rate
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At the same time, Professor Xu Yun also emphasized that the release of the consensus: ➤The first reminder that clinical diagnosis and treatment should be individualized and precise
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➤Second, the previous early evaluation of ischemic penumbra was like "blind people touching the elephant", and this version of the consensus provides a more accurate and effective evaluation method to help clinical judge whether the ischemic penumbra exists, where, and how large; ➤The third brings some new diagnosis and treatment concepts.
For example, we may have observed the improvement effect of Ureklin on collateral circulation in clinical practice before gradually understanding its mechanism of action through basic research, which suggests Doctors need to do some clinical research in addition to clinical work, and treat patients with the attitude of clinical research, which can bring greater benefits to patients
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Focusing on the ischemic penumbra is conducive to the advancement of precision medicine Professor Yu Shengyuan once again emphasized that the ischemic penumbra is a damaged but salvageable area between the infarct area and normal brain tissue, and is the key to the treatment of acute cerebral infarction , Which is also the focus of clinical diagnosis and treatment
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Compared with other consensus on cerebrovascular diseases, this is the first version of the consensus that focuses on the ischemic penumbra
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The formation of this version of the consensus provides an objective basis for precision medicine: ➤ Early and accurate assessment of the ischemic penumbra can help determine whether different treatment methods have clinical value
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If the early evaluation finds that the patient no longer has an ischemic penumbra, blindly performing vascular recanalization therapy may only increase the risk of bleeding, and will not have any significance in reducing the lesion and improving the patient's prognosis
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➤If the patient is unable to achieve reperfusion through revascularization, can we consider improving the collateral circulation or other comprehensive treatments to save the penumbra? This also requires early assessment of the ischemic penumbra as a basis
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➤In the past, it was believed that the bleeding risk of thrombolysis over time window was great, but now it is found that the penumbra of different patients is different, and there may still be therapeutic value beyond the time window
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Therefore, early assessment of the penumbra can make subsequent treatment more targeted
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➤Precision and individualized medical treatment will also have economic effects
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Doing what should be done and not doing what should not be done also ensures the reliability and safety of clinical diagnosis and treatment
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In this regard, Professor Xu Yun put forward the following point of view: The uniqueness of this version of consensus is that it achieves precise and individualized treatment
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The previous guidelines are standardized treatment recommendations for all patients
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However, there are individual differences between different patients.
If the patient's own collateral circulation is in good condition, the effect of standardized treatment will be good; if the patient's collateral circulation is not good, only give standardized treatment and ignore the evaluation and treatment of collateral circulation, the effect may be possible It's not good
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The publication of this version of the consensus reminds us that while applying standardized treatment, we must also pay attention to the patient's collateral circulation status.
Improving collateral circulation treatment through individualization may lead to a better prognosis for patients
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How to accurately evaluate and treat ischemic penumbra? The consensus content is worth referring to.
Multiple factors affect the dynamic changes of the ischemic penumbra.
The collateral circulation is particularly important.
Professor Wu Bo and Professor Wu Bo introduced in the interview that there are many factors affecting the ischemic penumbra: ➤The first is the duration of ischemia.
The longer the ischemic time, the ischemic penumbra will gradually transform into the infarct core, so it is very important to shorten the ischemic time; ➤Secondly, the situation of collateral compensation, patients with better collateral compensation, the ischemic tolerance time Longer, patients with poorly established collateral circulation, the ischemic tolerance time is very short; ➤The third is the general condition of the patient, such as high blood pressure, diabetes, or older age, these risk factors will lead to the automatic blood vessel The regulation mechanism is affected, which in turn affects the survival time of the ischemic penumbra; ➤Fourth is the complications of diseases and strokes, such as lung or urinary tract infections after a stroke, resulting in increased body temperature, or other diseases of the heart and kidney system.
It will also affect the survival of the ischemic penumbra
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➤In addition, there are artificial intervention treatments: ①Use methods such as dissolving and removing thrombus to open the occluded blood vessel as soon as possible, restore blood flow and reperfusion, and save the brain tissue in the ischemic penumbra; ②Use drugs to improve the ischemic and hypoxic tolerance of the brain tissue Ability to improve collateral circulation and prolong the survival time of the penumbra
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Professor Xu Yun pointed out that the collateral circulation is the key to the ischemic penumbra among the above-mentioned influencing factors.
The collateral circulation is closely related to the occurrence, development and outcome of all types of stroke
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➤From the perspective of diagnosis, early and accurate assessment of the patient's collateral circulation status is conducive to strengthening the pertinence of subsequent treatment
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➤From the perspective of treatment, for patients with poor collateral circulation, improving their collateral circulation can save lives, improve prognosis, and improve the quality of life
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Professor Xie Peng said that the evaluation and treatment of collateral circulation provides a new treatment concept for the clinic, that is, when evaluating the patient’s state, one should not only focus on the main blood supply artery in the infarct area, but also the side of the peripheral blood vessel formation.
The branches are regarded as a whole
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Through the assessment and treatment of the first, second and third grade collateral circulation, the patient's collateral circulation can be improved, and the brain tissue can be protected and the ischemic penumbra can be saved.

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Imaging has helped the concept of ischemic penumbra from basic research to clinical, but the collateral circulation assessment system needs to be improved.
Professor Song Haiqing’s clinical imaging evaluation of ischemic penumbra, Professor Song Haiqing said in an interview that imaging technology is accurate Basis for evaluating ischemic penumbra: ➤PET is the "gold standard" for evaluating ischemic penumbra, but its clinical application is inconvenient
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In recent years, various "mismatches" shown in CT and MRI have been used more clinically to assess ischemic penumbra
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➤In the beginning, we mainly used the "mismatch" of DWI and PWI to determine the penumbra area, but there were many false negatives and false positives in this area, which caused a big clinical confusion
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Therefore, in the past there was an interesting saying in the imaging department: Diffusion (ie DWI) plus Peffusion (ie PWI) equals confusion
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In addition, PWI examination requires injection of contrast medium, which is more inconvenient to use
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➤Of course, CT also has some limitations.
For example, the penumbra range of the posterior circulation area is not as accurate as that of the anterior circulation area; CT examination will also increase the radiation dose
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Therefore, imaging techniques that are more suitable for clinical application have gradually been developed, such as the use of MRI, FLAIR and DWI that do not require injection of contrast agents, and the "mismatch" between images and clinical symptoms to determine the penumbra.
Existence greatly expands the way we judge ischemic penumbra
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➤In order to change the problem that the naked eye is not accurate enough to judge the ischemic penumbra, the use of artificial intelligence to interpret images to assist clinical decision-making is also a future trend
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In this version of the consensus, everything from commonly used clinical imaging methods to rapidly developing artificial intelligence is included for the reference of the majority of front-line doctors, providing a basis for the promotion of the concept of "organizational window instead of time window", and bringing more patients To benefit
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Professor Zeng Jinsheng also gave us a comprehensive introduction to the application and development of imaging evaluation technology for ischemic penumbra, and made the following supplements: ➤In the absence of multimodal imaging evaluation conditions, it can pass conventional CT/MR imaging infarction The core and clinical symptoms are "mismatched" to initially and indirectly reflect the existence of the ischemic penumbra, but the definition of the threshold still needs further verification
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For example, ①When the patient's NIHSS score is higher, but the imaging examination reveals a smaller core infarct, it suggests that there is a larger ischemic penumbra
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②Patients with NIHSS≥6 and ASPECTS≥6, or NIHSS≥8 points and DWI hyperintensity ≤25m, suggest that there is an ischemic penumbra, intravascular treatment may be considered within the time window, and no perfusion imaging is necessary.
Other imaging evaluations
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➤The continuous improvement of post-processing software and artificial intelligence post-processing system has also gradually developed the evaluation of infarct core and ischemic penumbra from qualitative to rapid and accurate quantitative mode
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It has the following advantages: ① assist clinicians to quickly read images and accurately identify acute vascular occlusion; ② help early and accurate calculation of the infarct core and ischemic penumbra volume; ③ fast, fully automatic and quantitative determination can be made, making up for subjective Defects in judgment
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At present, the artificial intelligence-assisted analysis software-RAPID has also been widely used in large-scale clinical randomized controlled studies such as EXTEND-IA and DEFUSE-3, but it still needs to be popularized in various stroke centers in China
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➤The evaluation of collateral circulation is helpful to judge the outcome of ischemic penumbra, but the current evaluation of collateral circulation still lacks a unified imaging evaluation system, and the accuracy of various evaluation methods needs to be verified
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Regarding the last point mentioned by Professor Zeng, Professor Song Haiqing said in an interview that from a research perspective, everyone agrees that collateral circulation is an important factor affecting the ischemic penumbra.
Patients with good collateral circulation are The dark zone may last longer and the prognosis is better
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But the question is how to accurately assess the patient's collateral circulation status? At present, DSA is considered to be the "gold standard" for assessing collateral circulation, but DSA is an invasive examination that also requires injection of contrast agents, which cannot be achieved quickly in emergency conditions
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DSA and CT, MRI and other technologies cannot replace each other
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When conditions permit, it is still recommended that doctors provide DSA to determine the patient's collateral circulation
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However, in the future, it may be necessary to explore better and faster methods to assess collateral circulation, help clinically accurately screen patients, and benefit more patients
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In this regard, Professor Xu Yun’s view is also worthy of our deep consideration.
Professor Xu said that we cannot wait for all the technologies to be perfected before starting clinical practice.
When it can be 80% accurate and reliable, we can consider popularization and application; clinical research In the continuous development and advancement, even if we think that we have achieved 100% now, it may be only 80% in a few years
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If you have concerns about a single evaluation method, you can consider combining two or three evaluation methods to help make clinical decisions
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The rescue of ischemic penumbra should focus on multi-dimensional comprehensive treatment.
Improving the collateral circulation is an important assistant, Professor Wu Bo said.
For the treatment of ischemic penumbra, this version of the consensus recommends from many aspects: ➤The first is Vascular recanalization treatment
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Including two specific treatment options: ①Using alteplase or urokinase and other drugs for intravenous thrombolysis to disintegrate the thrombus and recanalize the blood vessels; ②If it is a large vessel occlusion, you can use catheter aspiration or stent removal, etc.
Interventional means restore blood flow and save the ischemic penumbra
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➤The second is to improve the treatment of collateral circulation
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Since the collateral circulation is an important factor affecting the ischemic penumbra, the application of drugs to improve the collateral circulation, such as Ureklin, can help expand the blood vessels in the ischemic area and save the ischemic penumbra
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➤Thirdly, anti-platelet or anticoagulation therapy can be used to prevent stroke recurrence regardless of major vessel occlusion or cardiogenic embolism; there are also a few studies that these drugs can play an anti-inflammatory effect on saving the ischemic penumbra.
A certain effect
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➤The fourth is neuroprotective therapy
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However, there is currently less relevant clinical evidence, and more clinical studies are needed in the future to continue to explore the effects of neuroprotective agents on the ischemic penumbra
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➤Fifth, the treatment of concomitant diseases and stroke complications is also very important
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Professor Yu Shengyuan also expressed similar views in the interview.
At the same time, he emphasized that treatment should be carried out from multiple dimensions and multiple targets, as far as possible to restore the neurons in the penumbra area to normal and reduce their transformation into the infarct area
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In addition, among the above treatments, Urekline is a commonly used drug in the treatment of collateral circulation.
From the perspective of its mechanism of action, Professor Wu Bo also introduced us the possible benefits of Urekline for patients: ➤First, promote angiogenesis and improve brain structure reserve; ➤Second, enhance the tolerance of brain tissue to ischemia and hypoxia, reduce the consumption of glucose and oxygen by ischemic tissue, improve its survival ability, and improve brain metabolic reserve;➤ Thirdly, it helps to improve the cerebral blood flow regulation ability in the ischemic area and improve the brain function reserve; ➤Fourth, there are basic researches that Ureklin can improve the cerebral blood flow reserve; ➤The fifth clinical practice found that Ureklin can also improve Neurological deficits can improve the quality of life of patients.
At the same time, Professor Wu Bo emphasized that the treatment of ischemic stroke is a comprehensive treatment.
Remember that you cannot treat only a certain point at a certain stage.
Instead, you should adhere to sequential treatment.
The primary treatment is still reperfusion, combined with drugs with different mechanisms of action, can achieve the greatest improvement in disability and reduce deaths that clinically pursue, and maximize the benefits for patients
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The future can be expected.
The penumbra is opening up a broad space for stroke diagnosis and treatment.
Talking about the future of imaging evaluation technology for ischemic penumbra, Professor Song Haiqing said: ➤The imaging technology for penumbra evaluation has been developed.
Relatively mature, more work in the future may lie in popularization and application to improve the availability of imaging technology
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➤How to simplify the process and speed up the imaging examination is also a clinical challenge
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If all imaging examinations can be performed like CT plain scans, with only a little time extension, without affecting the entire treatment process, it will be of great help to clinical work
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➤With the advancement of technology, the combination of artificial intelligence interpretation results will help to unify the evaluation standards, and prevent doctors' understanding deviations from affecting the rapid promotion and application of imaging technology
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Professor Xie Peng said that the main purpose of writing this consensus is to broaden the horizons of doctors, telling them not to stick to thrombolysis treatment in the acute phase and within the time window, let alone give up those patients who thought that treatment had little hope in the past
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Modern imaging techniques have been able to effectively assess the ischemic penumbra, and salvaging the ischemic penumbra through treatments such as improving collateral circulation can also bring the hope of rapid recovery or even significant improvement for patients, benefiting more patients
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Since the consensus is to be written twenty or thirty years after the concept of ischemic penumbra was proposed, our goal should not only be locked in the original treatment time window, but also focus on the broader treatment space outside the time window
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Finally, Professor Zeng Jinsheng concluded: ➤The main purpose of acute cerebral infarction treatment is to save the ischemic penumbra, and the focus of treatment is to open and occlude blood vessels early, protect and open collateral circulation, and protect ischemic nerve tissue
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➤Although the difference between the cerebral oxygen metabolism rate shown by PET and CBF is still the gold standard for evaluating ischemic penumbra, the core "mismatch" of ischemic perfusion/infarction based on imaging techniques such as CT or MRI has become clinical A simple and fast method for evaluating ischemic penumbra, and can guide clinical treatment
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➤With the advancement of diagnosis and treatment methods in the future, it is expected that the ischemic penumbra will be evaluated and rescued more effectively, and the prognosis of acute cerebral infarction will be improved
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