Various therapeutic measures (intravenous thrombolysis, mechanical thrombectomy, etc.) centered on vascular recanalization within the time window of acute cerebral infarction are mainly to save the ischemic Nerve cells with abnormal function but not yet dead due to injury can help reduce the degree of functional damage of patients and promote the recovery of nerve function.
The nerve tissue surrounding the infarct, which still has a chance for treatment, is generally considered to be the “ischemic penumbra”.
The content of this article refers to the “Chinese Expert Consensus 2021 on the Clinical Evaluation and Treatment of Ischemic Penumbra in Acute Cerebral Infarction”, which was compiled by the Cerebrovascular Disease Group of the Neurology Branch of the Chinese Medical Doctor Association.
1 ischemic halfWhat does the dark band mean?
Currently, it is believed that ischemic penumbra refers to the area of low blood flow around the infarct in the same vascular supply area as the cerebral infarction core, where nerve cells Physiological and biochemical abnormalities occur due to ischemia and lead to dysfunction, but not yet death. Timely improvement of hypoperfusion can return to normal, otherwise it may progress to infarction and aggravate brain damage.
Traditionally, normal blood supply brain tissue and ischemic brain tissue are distinguished by the degree of reduction in Cerebral blood flow (CBF) >, the latter can be further divided into three regions: mild ischemia without dysfunction, ischemic penumbra with dysfunction, and infarction.
However, studies have found that the determination of the ischemic penumbra by the absolute threshold of CBF alone is not reliable. It is believed that it is more accurate to distinguish ischemic tissue by the “mismatch” between neuronal protein synthesis and adenosine triphosphate (ATP) production. However, based on the limitations of observation methods and conditions, this method to determine the ischemic penumbrahas not been used clinically.
2 ischemic penumbraPathophysiological changes and clinical significance
There is a series of dynamic changes in the ischemia-hypoxia cascade in the ischemic penumbra. On the one hand, cell depolarization, oxygen free radical damage, and excitatory amino acid toxicity appeared several minutes after CBF decreased, and lasted for several days, resulting in inhibition of protein synthesis;
If CBF is not effectively improved, the ischemia-induced inflammatory response further leads to impaired cellular ATP synthesis, leading to neuronal death, and the ischemic penumbra transforms into infarction. On the other hand, the body can produce relevant protective mechanisms to delay ischemic damage.
Based on the above pathophysiological process, studies have found that the treatment of intravenous thrombolysis or vascular thrombectomy, which mainly focuses on restoring blood perfusion in the early stage of cerebral infarction, is the most effective treatment for cerebral infarction. The most effective treatment for acute cerebral infarction.
3 Ischemic penumbraClinical predictors and influencing factors
It is inaccurate to predict the ischemic penumbra solely based on changes in clinical symptoms and signs. There is a clinical/imaging “mismatch” phenomenon within 6 hours after the onset of acute cerebral infarction in the blood supply area of the internal carotid artery, that is, severe neurological deficit (high NIHSS score) and small infarction on imaging, which may indicate The ischemic penumbra is present.
The following factors affect the dynamic changes of the ischemic penumbra:
1) Ischemic penumbra time: Ischemic penumbra may still exist within 24 hours after cerebral infarction, but The accepted time to benefit from intravenous thrombolysis in saving the ischemic penumbra is 4.5 hours from onset.
2) Compensation of collateral circulation: A good collateral circulation can help delay the transformation of the ischemic penumbra into infarction, and the volume of the infarct core increases little.
3) Risk factors for cerebrovascular disease: Old age, blood pressure fluctuation, hyperglycemia, hyperlipidemia, etc. can accelerate the transformation of ischemic penumbra into infarction.
4) Concomitant diseases and stroke complications: Infection, electrolyte imbalance, gastrointestinal bleeding, etc., can accelerate the transformation of the ischemic penumbra into infarction.
5) Neuroprotective therapy: Such as improving collateral circulation, reducing tissue metabolism, inhibiting cellular hypoxia depolarization, reducing inflammatory response, etc., theoretically it can delay The ischemic penumbra progresses to infarction.
Recommendations:
1) In the acute stage of large artery occlusive cerebral infarction, neurological deficit is mild, but early neurological deterioration occurs or neurological deficit is severe but imaging infarction occurs Small lesions indicate that the ischemic penumbra may exist, and clinical identification should be strengthened (level III recommendation, level of evidence C).
2) The ischemic penumbra is influenced by factors such as ischemia duration, cerebral collateral circulation, risk factors for cerebrovascular disease, co-morbidities and stroke complications The dynamic changes of the disease should be paid attention to and actively intervened (level II recommendation, level C evidence).
4 Clinical of the ischemic penumbraimaging assessment
Currently, imaging “mismatch” or clinical symptoms and imaging “mismatch” are often used in clinical practice to replace the ischemic penumbra defined by histology to guide treatment decisions for acute cerebral infarction and prognosis assessment. PET is the gold standard for assessing the ischemic penumbra, but it has poor clinical performance. Currently, CT or MRI techniques are often used.
01. Imaging-based “mismatchmatch” approach
1)CT Mode
Multimodal CT includes CT plain scan, CT perfusion (CTP) and CT angiography (CTA), in which CTP can evaluate cerebral hemodynamic changes It can accurately reflect the degree of vascularization and blood perfusion in brain tissue;
The perfusion parameters include CBF, cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), residual Time to maximum of the residual function (Tmax), etc.
Assessment of the ischemic penumbra is mostly based on CTP perfusion maps, a subjective assessment of the “mismatch” between the infarct core and areas of abnormal perfusion. CBF/CBV “mismatch” is the easiest and most practical way to quickly assess the ischemic penumbra in the current emergency state.
Many post-perfusion software have added the Tmax parameter as a sensitive parameter for quantitative evaluation of the hypoperfusion zone and infarct core, usually Tmax > 6 seconds or relative MTT (relative MTT, rMTT) value> 145% as the threshold of ischemic penumbra, relative CBF (relative CBF, rCBF) value
2) MRIMode
Methods such as
MR perfusion-weighted imaging(PWI)/DWI “mismatch” and FLAIR/DWI “mismatch”, are highly efficient Complete a clinical assessment of the ischemic penumbra.
In MR mode, the ischemic penumbra is qualitatively assessed using a CBF/DWI “mismatch”, usually with DWI hyperintensity as the infarct core;
PWI Tmax > 6 seconds or rMTT > 145% as the ischemic penumbra threshold and rCBF
FLAIR/DWI “mismatch” refers to high signal on DWI with no obvious signal change in the corresponding area on FLAIR. This method does not belong to the imaging evaluation method of the ischemic penumbra, but it can effectively identify the stroke within 4.5 hours of onset in patients with onset stroke and stroke of unknown onset. patients, indirect judgment the presence of the ischemic penumbra.
02. Assessment of “mismatch” between clinical symptoms and imaging
In the absence of multimodal imaging assessment, the presence of the ischemic penumbra can be indirectly reflected by the clinical “mismatch” of the infarct core on conventional CT/MRI imaging.
If NIHSS ≥ 6 with ASPECTS ≥ 6; or NIHSS ≥ 8 with DWI hyperintense volume ≤ 25 mL, it suggests a possible ischemic penumbra.
03. AI-assisted assessment of ischemic penumbra
Artificial intelligence-assisted analysis software such as RAPID, MIstar, eStroke, and F-Stroke can help clinicians read images quickly and accurately identify and calculate the ischemic penumbra and infarct core volume. The method has not been widely popularized in our country.
04. Assessment of collateral circulation
Collateral circulation capacity is an important factor in determining the final infarct volume and ischemic penumbra volume. Imaging assessment of collateral circulation in acute cerebral infarction plays an important role.
RecommendedComments:
1) For patients within 4.5 hours of the onset of intravenous thrombolysis, unenhanced CT scan should be performed as soon as possible strong>Excluding bleeding, multimodal imaging is not recommended to evaluate the ischemic penumbra to delay the time of intravenous thrombolysis (Class I recommendation, Level A evidence).
2) For patients with unknown time of onset or more than 4.5 hours from the last normal time, MRI examination with FLAIR/ DWI “mismatch” to assess the ischemic penumbra and to screen patients who may benefit from intravenous thrombolysis (Class II, Level of Evidence B).
3) For patients who are planning to undergo endovascular thrombectomy within 6 hours of onset, CTA or MRA should be performed to confirm the vascular condition (Class I Recommendation, Level A Evidence);
When NIHSS ≥ 6 points and ASPECTS ≥ 6 points, or NIHSS ≥ 8 points and DWI hyperintensity volume ≤ according to clinical symptoms, CT scan and CTA (or MRI and MRA) results For patients with 25 mL volume, endovascular thrombectomy can be considered without further imaging evaluation of the ischemic penumbra such as perfusion imaging (Class I recommendation, Level of evidence B).
4) For patients whose onset time is 6-16 h, CBF/CBV “mismatch” in CT mode should be used to characterize Assess the ischemic penumbra;
Or refer to DAWN or DEFUSE-3 research criteria: Tmax > 6 s and rCBF 1.8, and infarct core ≤ 70 mL, ischemic penumbra volume ≥ 15 mLSelect patients who are suitable for thrombectomy (Class I recommendation, Level A evidence).
5) For patients with onset time between 16 and 24 h or unknown time of onset, CT mode should be used to qualitatively evaluate ischemia with CBF/CBV “mismatch” In the penumbra, patients who are suitable for thrombectomy can be screened according to the DAWN research criteria (level II recommendation, level B evidence).
6) AI-assisted analysis software facilitates rapid, fully automated quantitative assessment of infarct core and ischemic penumbra volume (Class II, Level of Evidence B ).
7) Evaluation of collateral circulation can help determine the outcome of the ischemic penumbra (Class II, Level of Evidence B).
5 ischemic hemispheresTreatment of dark bands
Thrombolysis or Thrombectomy and other recanalization treatments are the main methods to save the ischemic penumbra. At the same time, it is also necessary to actively control harmful factors such as hyperglycemia, treat associated diseases such as pulmonary infection and cardiac insufficiency, and take various measures including improving collateral circulation to create conditions for reversing the ischemic penumbra.
Recommendations:
1) For acute cerebral infarction with onset time within 4.5 hours, intravenous thrombolysis or bridging endovascular thrombectomy is recommended if necessary (Class I recommendation, A Level of evidence); if the onset time exceeds 4.5 hours or the onset time is unknown, there is a “mismatch” assessed by multimodal imaging, and intravenous thrombolysis can be performed (Class II recommendation, Level of evidence B).
2) For acute anterior circulation large vessel occlusive cerebral infarction within 6 hours of onset, endovascular thrombectomy should be performed as soon as possible if there are indications and no surgical contraindication Treatment (Class I, Level of Evidence A);
For onset of more than 6 hours [6 to 16 hours (class I recommendation, level of evidence A), 16 to 24 hours (class II recommendation, level of evidence B)] or unknown time to onset (II Level of recommendation, level of evidence B) with large vessel occlusion in the anterior circulation, and if there is an ischemic penumbra after strict clinical and imaging evaluation, endovascular thrombectomy can be performed.
3) For patients beyond the time window of thrombolysis or endovascular thrombectomy or unconditional revascularization therapy, early individualized use of ureclin or Drugs such as butylphthalide promote the opening of collateral circulation to save the ischemic penumbra (Class II, Level of Evidence B).
4) Reasonable blood pressure management and timely antiplatelet or anticoagulation therapy can help improve blood perfusion in the ischemic penumbra (Class I recommendation, A level of evidence).
5) Active control of harmful factors such as hyperglycemia and hyperthermia as well as various complications of acute cerebral infarction is beneficial to protect the ischemic penumbra (Class II recommendation, level of evidence B).
6) The effect of neuroprotective agents on the ischemic penumbra is unclear. Edaravone and dexbornol block the cerebral ischemia cascade through multiple targets, and its protective effect on the ischemic penumbra deserves further clinical exploration (level II recommendation, level B evidence).
6 Outlook
Saving the ischemic penumbra is the main purpose of the treatment of acute cerebral infarction. The treatment focuses on early opening of occluded blood vessels, protection and opening of collateral circulation, and protection of ischemic tissue.
In the future, with the advancement of diagnosis and treatment methods, there will be more rapid, accurate and effective methods to assess and save the ischemic penumbra and improve the prognosis of acute cerebral infarction.
References:
“Chinese Expert Consensus on Clinical Evaluation and Treatment of Ischemic Penumbra in Acute Cerebral Infarction 2021” Cerebrovascular Disease Group of Neurosurgery Branch of Chinese Medical Doctor Association
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