Clinical evaluation and treatment of ischemic penumbra of acute cerebral infarction, a list of the latest expert consensus recommendations

In the acute phase of cerebral infarction, various treatment measures centered on vascular recanalization are mainly to save the functionally abnormal but not dead nerve cells around the infarct due to ischemic injury, restore them to normal and promote the recovery of nerve function
.

The nerve tissue around the infarct, which still has a chance of treatment, is generally considered to belong to the "ischemic penumbra"
.

Ischemic penumbra has become the focus of acute cerebral infarction, and its clinical evaluation and treatment are highly valued by vascular neurology and related physicians
.

Under the leadership of the Neurologist Branch of the Chinese Medical Doctor Association, the cerebrovascular disease committee (scientific group) organized experts in related fields in China to write the following consensus after repeated discussions, for domestic counterparts to evaluate and treat acute cerebral infarction in clinical practice Refer to when the blood penumbra
.

The concept of ischemic penumbra is currently believed that ischemic penumbra refers to the area of ​​hypoperfusion around the infarct in the same blood vessel supply area as the core of cerebral infarction.
In this area, nerve cells have physiological and biochemical abnormalities and lead to function due to ischemia.
Obstacles, but have not yet died, timely improvement of hypoperfusion can return to normal, otherwise it may worsen and progress to infarcts and aggravate brain damage
.

After half a century of animal experiments and clinical research, especially with the rapid development of neuroimaging technology in recent years, it has become possible to determine the clinically significant ischemic penumbra, and the concept of ischemic penumbra gradually tends to Unanimous
.

Pathophysiological changes of ischemic penumbra There are a series of dynamic changes of ischemia-hypoxic cascade in the ischemic penumbra
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On the one hand, a few minutes to a few hours after the cerebral blood flow (CBF) is reduced, cell depolarization, oxygen free radical damage, excitatory amino acid toxicity, and tissue acidification can occur, and can continue for several days, leading to cell protein synthesis Inhibition: If the CBF is not effectively improved, the ischemia-induced inflammatory response further causes cell adenosine triphosphate (ATP) synthesis disorder and neuronal death, and the ischemic penumbra transforms into an infarct focus
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On the other hand, increased expression of endogenous proteins such as hypoxia-inducible factor-1, erythropoietin, transforming growth factor and interferon regulatory factor can reduce ischemic damage and delay the deterioration of the ischemic penumbra to infarction Stove
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 The clinical prediction and influencing factors of the ischemic penumbra have the following factors that affect the dynamic changes of the ischemic penumbra: ① Duration of ischemia: Although the ischemic penumbra can exist within 24 hours after cerebral infarction, it is currently recognized as a vein The benefit time of thrombolysis to save the ischemic penumbra is within 4.
5h of onset, and more than 4.
5h.
Imaging is required to evaluate the size of the ischemic penumbra to determine whether the recanalization treatment is beneficial
.

 ②Collateral circulation compensatory ability: The size of the infarct is not only affected by the occluded blood vessel, but the cerebral collateral circulation is also an important factor in determining the final volume of the infarct and ischemic penumbra
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Good collateral circulation helps to save the ischemic penumbra and prevent the expansion of cerebral infarction
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 ③ Risk factors for cerebrovascular disease: advanced age, high blood pressure fluctuations, high blood sugar and high blood lipids can damage collateral circulation and accelerate the transformation of ischemic penumbra into infarcts
.

 ④Complications of diseases and stroke: cerebral infarction accompanied by organ dysfunction, severe infection, electrolyte imbalance, gastrointestinal hemorrhage, high fever, secondary epilepsy or hemorrhagic transformation of infarct focus, etc.
, can affect the blood oxygen metabolism of brain tissue.
Exacerbate brain damage and accelerate the transformation of ischemic penumbra into infarcts
.

 ⑤Neuroprotective intervention: mainly by improving the oxygen supply of the ischemic penumbra, improving collateral circulation, reducing tissue metabolism, inhibiting cell hypoxia depolarization and reducing inflammation, etc.
, to achieve "freezing stop" the ischemic penumbra.
The purpose of slowing down its transformation into infarcts
.

 Recommendations ① In the acute stage of aortic occlusive cerebral infarction, the neurological deficit is mild, but when the early neurological function deteriorates or the neurological deficit is severe but the imaging infarction is small, it indicates that the ischemic penumbra may exist, and the clinical practice should be strengthened Identification (level III recommendation, level C evidence)
.

 ②Factors such as duration of ischemia, cerebral collateral circulation, risk factors for cerebrovascular disease, concomitant diseases and stroke complications affect the dynamic changes of the ischemic penumbra, which should be paid attention to and actively intervened (level II recommendation, level C evidence )
.

Recommendations for clinical imaging evaluation of ischemic penumbra ① For patients who are scheduled to undergo intravenous thrombolysis within 4.
5 hours of onset, CT scan should be performed as soon as possible to rule out bleeding.
Multimodal imaging examination is not recommended to evaluate ischemic penumbra.
Delay in intravenous thrombolysis (level I recommendation, level A evidence)
.

 ②For patients whose onset time is unknown or more than 4.
5 hours from the last normal time, MRI can be considered, FLAIR/DWI "mismatch" is used to assess the ischemic penumbra, and patients who may benefit from intravenous thrombolysis (level II) Recommendation, Level B evidence)
.

 ③For patients who are planning to receive endovascular thrombus removal treatment within 6 hours of onset, CTA or MRA should be performed to confirm the vascular condition (level I recommendation, level A evidence); based on clinical symptoms, CT scan and CTA (or MRI and MRA) results When NIHSS ≥ 6 points and ASPECTS ≥ 6 points, or NIHSS ≥ 8 points and DWI high signal volume ≤ 25 mL, intravascular thrombus removal can be considered, and other imaging evaluation such as perfusion imaging is not necessary for the ischemic penumbra ( Level I recommendation, level B evidence)
.

 ④For patients whose onset time is 6 to 16 hours, the CBF/CBV "mismatch" in the CT mode should be used to qualitatively evaluate the ischemic penumbra; or refer to the DAWN or DEFUSE-3 research standards: Tmax>6s and rCBF<30% The ischemic penumbra was evaluated quantitatively, and patients with low perfusion volume/infarct core> 1.
8, infarct core ≤ 70 mL and ischemic penumbra volume ≥ 15 mL were used to screen patients suitable for thrombus removal (level I recommendation, level A evidence)
.

 ⑤For patients whose onset time is between 16 and 24 hours or whose onset time is unknown, the CBF/CBV "mismatch" in the CT mode should be used to qualitatively evaluate the ischemic penumbra.
The DAWN research standards can be used to screen patients suitable for thrombus removal (level II recommendation) , Level B evidence)
.

 ⑥The artificial intelligence-assisted analysis software helps to quickly and fully automatically evaluate the volume of the infarct core and ischemic penumbra (level II recommendation, level B evidence)
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 ⑦The evaluation of collateral circulation is helpful to determine the outcome of ischemic penumbra (level II recommendation, level B evidence)
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Recommendations for the treatment of ischemic penumbra ①For acute cerebral infarction with an onset time of less than 4.
5 hours, intravenous thrombolysis or bridging intravascular thrombus removal is recommended if necessary (level I recommendation, level A evidence); the onset time exceeds 4.
5 hours Or if the time of onset is unknown, there is a "mismatch" after multimodal imaging assessment, and intravenous thrombolysis is feasible (level II recommendation, level B evidence)
.

 ②For acute anterior circulation large vessel occlusive cerebral infarction within 6 hours of onset, if there are indications and no surgical contraindications, endovascular thrombus removal should be performed as soon as possible (level I recommendation, level A evidence); for onset of more than 6h [6～16h (Level I recommendation, Level A evidence), 16 to 24 hours (Level II recommendation, Level B evidence)] or the onset of unknown time (Level II recommendation, Level B evidence) anterior circulation large vessel occlusion, existing after strict clinical and imaging evaluation Patients with ischemic penumbra may be treated with intravascular thrombus removal
.

 ③For patients who have exceeded the time window for thrombolysis or intravascular thrombectomy or unconditionally undergo vascular recanalization therapy, drugs such as ureclin or butylphthalide can be individualized early to promote the opening of collateral circulation to save the ischemic penumbra (Level II recommendation, Level B evidence)
.

 ④Reasonable management of blood pressure and timely antiplatelet or anticoagulation therapy can help improve the blood perfusion of the penumbra (level I recommendation, level A evidence)
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 ⑤ Active control of harmful factors such as hyperglycemia and high body temperature, as well as various complications in the acute phase of cerebral infarction, is conducive to protecting the ischemic penumbra (level II recommendation, level B evidence)
.

 ⑥The effect of neuroprotective agents on ischemic penumbra is still unclear
.

Edaravone dexcamphanol blocks the cerebral ischemic cascade through multiple targets, and its protective effect on the ischemic penumbra is worthy of further clinical exploration (level II recommendation, level B evidence)
.

Yimaitong is compiled from: Cerebrovascular Disease Group of Neurologist Branch of Chinese Medical Doctor Association.
Clinical evaluation and treatment of ischemic penumbra of acute cerebral infarction.
Chinese expert consensus[J].
Chinese Journal of Nervous and Mental Diseases, 2021,47(6) :324-335.
DOI:10.
3969/j.
issn.
1002-0152.
2021.
06.
002.