Evaluation of collateral circulation of acute ischemic stroke and intervention in Chinese emergency department expert consensus

Acute ischemic stroke (AIS) has the characteristics of high morbidity, high fatality, high disability, high recurrence rate, and high cost, and early intravenous thrombolysis, endovascular treatment (EVT) and open collateral circulation in the time window are the three main ways
to achieve AIS blood flow reperfusion.
The concept of tissue window was proposed by adjusting the time window according to the collateral circulation compensation, which is a paradigm shift
in stroke reperfusion therapy.
It was found that collateral circulation was a predictor of the prognosis of AIS, and the vascular opening rate and prognosis were closely related to
collateral circulation.
In recent years, several studies have promoted the extension of the time window for vascular recanalization, especially in patients with AIS who cannot have intravenous thrombolysis beyond the time window (wake-up stroke), and collateral circulation assessment is important for the implementation and prognosis of intravenous thrombolysis and EVT
.

Due to time windows and contraindications, many patients with AIS do not have intravenous thrombolysis and EVT in the emergency department, so collateral circulation is one of
the main ways to achieve blood flow reperfusion 。 In order to further promote and standardize the evaluation and treatment of collateral circulation in patients with emergency AIS, the Emergency Branch of the Chinese Medical Association organized multidisciplinary experts from domestic emergency, neurology, neurosurgery, neurointervention, neuroimaging and other disciplines, combined with a large amount of evidence-based medical evidence, with reference to the norms and requirements formulated by the guidelines and consensus of the Chinese Journal of Emergency Medicine, using the Delphi survey method to formulate a consensus, and voting on each content by all experts participating in the consensus formulation on issues closely related to collateral circulation assessment and intervention.
and repeatedly discuss, adjust, and feedback on controversial issues until consensus is reached
.

01 Definition and influencing factors of lateral branch circulation of the brain

Cerebral collateral circulation refers to when the cerebral artery supplying blood supply is severely narrowed or occluded, the blood flow reaches the ischemic area through other blood vessels (collateral or newly formed vascular anastomosis), so that the ischemic tissue can be perfused to varying degrees, which is one of
the cerebral circulation compensation mechanisms.
Collateral circulation maintains blood circulation around the core area of infarct and is a major factor
in determining the final infarct volume and ischaemic semi-dark zone after AIS.
According to the compensatory pathway of blood flow, the cerebral collateral circulation is mainly divided into three levels: the first level is the primary cerebral collateral circulation compensation, that is, the Willis ring, which is the most important collateral circulation pathway in the skull and is a bridge between the main arteries in the skull, so that the left and right cerebral hemispheres and the blood flow of the anterior and posterior circulation communicate with each other; The secondary cerebral collateral circulation compensation mainly includes the ophthalmic artery and the primary leptomeningeal collateral, and when the compensation of the Willis ring cannot meet the blood supply demand, the secondary compensatory pathway comes into play; The tertiary collateral circulation compensation is neovascularization, and when secondary compensation still cannot meet the blood supply demand, neovascularization becomes the final collateral compensation pathway
.

The factors affecting the opening of the cerebral collateral circulation mainly include:(1) vascular variability The structural integrity of the collateral circulation is an important prerequisite for exerting its primary and secondary collateral circulation compensation ability, after severe stenosis and/or occlusion of the cerebral artery, the degree of collateral circulation establishment is closely related to the integrity of the Willis ring and the number of effective collateral circulation, and the establishment of multiple collateral circulation can significantly reduce the volume of infarct area; (2) Risk factors Advanced age, persistent hypertension, hyperlipidemia and hyperglycemia will reduce vascular regulation and endothelial function, resulting in a decrease in the establishment ability of tertiary collateral circulation compensation; (3) The size of the collateral circulation vascular diameter and chronic hypoperfusion have an important impact on
the collateral circulation compensation.
The heavier the stenosis, the slower the rate of occurrence and the better
the collateral circulation.
Patients with large vessel occlusion AIS with prior ipsilateral extracranial carotid stenosis tend to have better
collateral circulation.
Long-term hypoperfusion of the brain can lead to an increase in the concentration of various pro-angiogenic factors, which in turn promotes neoangiogenesis and the establishment
of collateral circulation.
The study found that patients with carotid atherosclerotic stroke had a wider collateral circulation and a better
prognosis at 90 days compared with patients with cardioembolic stroke.

Recommendation 1: Where available, the emergency physician should actively evaluate
the lateral branch circulation of the brain in patients with AIS who are elderly, persistently hypertensive, hyperlipidamic, and have decreased vasomodulatory capacity such as diabetes.

02 Lateral branch circulation assessment method

Imaging plays an important role
in assessing the status of the responsible vessels and collateral circulation in patients with AIS.
Cerebral angiography technologies include digital subtraction angiography (DSA), CT angiography (CTA), magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA).
Both can directly show the responsible vascular, primary and partial secondary collateral circulation
.

2.
1 DSA Evaluation

DSA is currently the most widely used imaging method
for grading collateral circulation.
As the gold standard for secondary and tertiary collateral evaluation, DSA primarily uses the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology ASTIN/SIR collateral circulation assessment system (Table 1).

。 Studies have confirmed that collateral vascular status can independently predict reperfusion, final infarct area and clinical prognosis; The better the collateral circulation, the higher the vascular recanalization rate, the smaller the infarction range, and the better
the clinical prognosis.

Table 1 DSA-based collateral circulation scoring system

DSA is also the most intuitive and highest-resolution method for assessing collateral circulation, allowing selective examination of different vessels, especially for the evaluation of pia mater collateral circulation, which cannot be replaced
by other methods.
Given that DSA is an invasive and expensive test, it is recommended that it can be combined with noninvasive imaging techniques to complement noninvasive imaging techniques and play an important role
in the assessment of the contralateral branch.

2.
2 CTA evaluation

Compared with the invasiveness and high cost of DSA, CTA is a rapid, non-invasive vascular imaging technique.
With high temporal and spatial resolution, the site of intracranial artery stenosis or occlusion and the compensatory range
of primary and secondary collateral circulation can be clearly visualized.
CTA assesses collateral circulation and predicts the prognosis
of AIS better than DSA.
In the initial vascular evaluation of AIS patients, the use of polyphasic CTAs instead of monophasic CTAs has important benefits: in addition to compensating for the delay in collateral circulation display in pathological conditions, it can also detect the condition of large vessel occlusion, features of collateral status, etc.
; It also has clear advantages
in terms of time, risk and economic benefits.
In addition, multi-phase CTAs have the advantage of maintaining rapid diagnostic time while allowing for a simpler, more direct assessment of collateral circulation, suitable for less experienced radiologists
.

At present, there are many collateral circulation assessment methods based on CTA, including Alberta stroke program early CT score (ASPECTS), Mitef score, Tan score, etc
.
ASPECTS is widely recommended by stroke guidelines at home and abroad, primarily to show blood flow supply through CTAs, and is used to screen patients with AIS who may have a semi-dark zone of ischemia and are suitable for EVT (table 2).

The collateral circulation defined by the Mitef score and the TAN score are independent predictors of the prognosis of
AIS.
In addition, noninvasive methods have been attempted for collateral circulation assessment
.
The study found that pia mater collateral pressure measurements correlated best with collateral circulation grading scales, and were more correlated with patient prognosis than other collateral circulation grading scales, and the larger the value, the better
the overall prognosis.

Table 2 CTA-based collateral circulation scoring system

Recommendation 2: ASTIN/SIR and ASPECTS scoring systems are the main assessment methods for DSA and CTA to assess lateral brain branch circulation, respectively; The ASPECTS scoring system is easy to use and is the primary method for
collateral circulation assessment in patients with AIS.

2.
3 MRI evaluation

MRI is also unique in assessing collateral circulation: it is highly
sensitive to the anterior communicating artery.
MRA multiphase imaging collateral map has some clinical reliability
for the evaluation of collateral circulation in patients with AIS.
The diffusion weighted imaging (DWI)-flfl uid-attenuated inversion-recover (FLAIR) and arterial spin labeling (ASL)-DWI double mismatch techniques of multimodal MRI can indirectly assess the time of onset, It can also evaluate whether there is a semi-dark zone of ischemia and scientifically guide the acute treatment
of patients with AIS with an unknown time window.
The FLAIR hyperintense vascular sign distal to the occludant artery, which represents a slow reverse flow of the collateral circulation of the pia mater and is generally thought to be associated with
hemodynamic impairment.
FLAIR vascular strength scores have been found to be a good indicator
of collateral circulation assessment.

Recommendation 3: DSA, CTA, MRI, and MRA are the mainstay of imaging tools for collateral circulation assessment of AIS, and CTA is the mainstay of
collateral circulation assessment in patients with emergency AIS when DSA is not available or is not available.

03 Collateral circulation, ischemic semi-dark zone and prognosis of AIS

3.
1 Collateral circulation and prognosis of AIS

The collateral circulation status is closely related to the prognosis of AIS: collateral circulation predicts the final infarct core, infarct progression rate, and efficacy of EVT; Good collateral circulation status is strongly associated
with a better clinical prognosis after smaller ischaemic infarctions, intravenous thrombolysis, and EVT.

(1) Prognostic assessment: The collateral circulation status is the main determinant of
ischemic core growth after intracranial large vessel blockage.
Collateral circulation status is assessed by the ratio of severely hypoperfusion volumes within CT perfusion (CTP) hypoperfusion zones, with worse collateral circulation and faster
ischemic core growth.
Patients with initial Willis ring incomplete development have a high stroke scale score (NIHSS score) and a low ASPECTS score, which are independent risk factors
for serious adverse outcomes of stroke.

Ischemic core growth rate = acute core volume at CTP / time to CTP from stroke onset

(2) Efficacy evaluation: collateral circulation is an important factor affecting treatment decisions, which provides an auxiliary basis
for further EVT.
A meta-analysis of patients with AIS with anterior circulation macrovascular occlusion showed a strong correlation between good collateral circulation and reperfusion, which significantly improved the success rate of reperfusion and reduced the incidence
of bleeding after mechanical embolectomy.
Effective collateral assessment facilitates better selection of
EVT.
Rapid EVT has been shown to improve neurological outcomes and reduce mortality in patients with proximal vascular occlusion, infarct nucleus, and moderate to good collateral circulation
in patients with AIS.

(3) Risk assessment: collateral circulation is an important determinant of the development of AIS in patients with atherosclerosis, and it is also the basic factor
for predicting the poor prognosis of AIS patients.
In patients with AIS with occlusion of the middle cerebral artery, CTA or CTP show poor collateral circulation and are often at higher
risk of bleeding after stroke.

3.
2 Ischemic semi-dark zone and prognosis of AIS

Ischemic penumbra refers to the blood flow hypoperfusion area around the infarction foci in the same vascular supply area as the core of cerebral infarction, where nerve cells cause physiological and biochemical abnormalities and cause dysfunction due to ischemia, but have not died, timely improvement of hypoperfusion can return to normal, otherwise it can worsen and progress to infarction foci and aggravate brain damage
.
The ischemic semi-dark zone is key to the prognosis of
patients with AIS.

Opening the collateral circulation at the first time can save the ischemic semi-dark zone, increase the volume of the semi-dark zone, reduce the area of ischemic infarction, and better improve the prognosis
of patients.
Studies have confirmed that the ischemic semi-dark zone is closely related to the collateral circulation, and good collateral circulation helps to save the ischemic semi-dark zone; The rate of infarct progression is closely related
to collateral scores.

Recommendation 4: The ischemic semi-dark zone is closely related to collateral circulation, both of which are important predictors of clinical outcomes in AIS and important factors influencing treatment decisions for AIS, and emergency physicians should evaluate
patients with AIS for collateral circulation and ischemic semi-dark zones whenever possible.

3.
3 Evaluation of collateral circulation and ischemic semi-dark zone

Emergency physicians can use imaging mismatches, mismatches between clinical symptoms and imaging, and artificial intelligence software to rapidly assess collateral circulation and ischemic semi-dark zones in patients with AIS to screen patients
for further thrombolysis and EVT.

(1) Imaging mismatch: IN ADDITION TO THE ASPECTS SCORE, THE MISMATCH BETWEEN DWI AND FLAIR ON MERI (THAT IS, THE DWI IS HYPERINTENSIVE, AND THE SIGNAL FROM THE CORRESPONDING AREA OF FLAIR IS NOT OBVIOUS) CAN BE USED AS THE MAIN METHOD
FOR ISCHEMIC SEMI-DARK ZONE EVALUATION IN AIS PATIENTS WITH UNCLEAR ONSET 。 Although this method is not an imaging method for ischemic semi-dark zone assessment, many studies have confirmed that it can more accurately and indirectly assess the ischemic semi-dark zone and collateral circulation, effectively identify patients with AIS within 4.
5 hours of onset, with an accuracy of 87%, and be used to guide safe and effective thrombolysis therapy in patients with unknown onset and awake stroke
.

(2) MISMATCH BETWEEN CLINICAL SYMPTOMS AND IMAGING: THE CORE INFARCT LESION OF MRI (MRI OR ASPECTS SCORE) AND THE PATIENT'S NEUROLOGICAL DEFICIT (NIHSS SCORE) SYMPTOMS DO NOT MATCH, THAT IS, WHEN THE PATIENT HAS SEVERE NEUROLOGICAL DEFICIT (HIGH NIHSS SCORE), BUT IMAGING SHOWS A SMALL CORE INFARCT AREA, SUCH AS NIHSS ≥ 6 POINTS AND ASPECT ≥ 6 POINTS, OR NIHSS ≥ 8 POINTS AND DWI HIGH SIGNAL VOLUME < 25 mL, INDICATING THE PRESENCE OF ISCHEMIC SEMI-DARK ZONE <b10>。 This is highly suggestive of good collateral circulation and large ischaemic semi-dark bands, and further EVT
may be considered within a time window.

(3) Artificial intelligence: AI-assisted analysis software can guide clinical and imaging physicians to quickly identify vascular occlusion, which can avoid subjective and quantitative assessment of ischemic semi-dark bands, such as the commonly used auxiliary analysis software RAPID has been applied to thrombolysis in emergency neurological defifi cits (EXTEND) and endovascular therapy after imaging evaluation using ischemic stroke 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3, DEFUSE 3) study with good results
.
The DEFFUSE-3 trial used artificial intelligence to screen for low perfusion volume/infarct core > 1.
8, infarct core < 70 mL, ischemic semi-dark zone> 15 mL as criteria for endovascular thrombectomy, and the results showed that EVT based on this was very effective and safe
.

Recommendation 5: Emergency physicians can use imaging mismatches, clinical and imaging mismatches, and artificial intelligence software to rapidly assess ischemic semi-dark zones and collateral circulation in AIS patients to screen patients for further thrombolysis and EVT
.

4 AIS implements the blood flow reperfusion method

In the acute phase of AIS, various treatment measures centered on recovery perfusion are mainly to rescue the nerve cells around the infarction that have abnormal function due to ischemic injury but have not yet died, restore them to normal and promote the recovery
of nerve function.
The most effective methods of restoring blood flow in the emergency department include intravenous thrombolysis, EVT, and open collateral circulation (algorithm 1).

4.
1 Intravenous thrombolysis

Intravenous thrombolysis is the first-line treatment for AIS, from the European Collaborative Acute Stroke Study (ECASS) in 1995 to the National Institute of Neurological dDiseases and Stroke (NINDS), to ECASS III in 2008.
The publication of the study finally confirmed that intravenous thrombolysis of 3~4.
5 h can still benefit
patients.
In 2012, the Third International Stroke Trial (IST-3) attempted to extend the time window for intravenous thrombolysis of alteplase to 6 hours, but failed but found that thrombolysis in some out-of-label patients, including older age, extended time window, and more severe stroke, did not increase the risk of
adverse prognosis.
SUBSEQUENT WAKE-UP STROKE (WAKE UP) STUDIES USED IMAGING TO SCREEN PATIENTS
WHO WOULD BENEFIT FROM INTRAVENOUS THROMBOLYTIC THERAPY.
EXTEND study Under the guidance of multimodal imaging, intravenous thrombolysis of 4.
5~9.
0 h significantly increased the good prognosis
of patients.

Based on the evidence from various studies, intravenous thrombolysis at 4.
5 h is still a grade A recommendation; Intravenous thrombolysis with alteplase is recommended
for patients with an out-of-time window and a CT or MRI core/perfusion mismatch, and a DWI-FLAIR mismatch in MRI who are not candidates or are not scheduled for mechanical thrombectomy.

4.
2 EVT

EVT is another powerful tool
for opening blood perfusion in patients with AIS.
A 2015 multicenter randomized clinical study of intravascular therapy for acute ischemic stroke in the Netherlands (MR CLEAN) demonstrated that EVT within 6 hours can significantly improve the prognosis
of patients with AIS 。 THE EXTENDIA STUDY DEMONSTRATED THAT EARLY MECHANICAL THROMBECTOMY IMPROVES PERFUSION AND PROMOTES EARLY NEUROLOGICAL RECOVERY
COMPARED WITH ALTEPLASE ALONE IN STROKE PATIENTS WITH STROKE WITH PROXIMAL LARGE VESSEL OCCLUSION AND CT PERFUSION SUGGESTING POTENTIAL TO SAVE BRAIN TISSUE.

The results of directarterial therapy for acute large vessel occlusive ischemic stroke (DIRECT) in China showed that compared with direct mechanical thrombectomy, there was no significant
difference in the efficacy of combined intravenous alteplase bridging mechanical thrombectomy in the treatment of AIS caused by intracranial anterior circulation large vessels 。 An EVT study for small core and anterior circulation proximal occlusion with emphasis on minimizing CT to recanalization time (ESCAPE) confirmed that patients with small infarct cores EVT improves neurologic outcomes in patients with AIS with proximal intracranial artery occlusion and moderate to good collateral circulation
.
The phased results of the above studies mainly lie in the selection of patients who may benefit, the use of multimodal imaging technology to exclude the central area of large infarcts or the poor circulatory condition of collateral branches, and the implementation of early blood flow reperfusion
of patients.

4.
3 Open collateral circulation

Opening collateral circulation is another important way to
achieve blood flow reperfusion.
The establishment of collateral circulation at the first time can restore and improve blood perfusion, save the semi-dark zone, and improve the prognosis
of patients' neurological function.
First of all, the focus of opening the collateral circulation is not the emboli or plaques that lead to vascular occlusion, but the restoration of blood flow in the ischemic area, increasing the blood supply around the central area of cerebral ischemia, and improving blood perfusion; The second is to extend the patient's treatment window and slow down the development of AIS; In addition, open collateral circulation can also affect the improvement or deterioration
of early clinical symptoms.
Multivariate analysis confirmed that patients with good collateral circulation had a smaller final infarct volume and a higher
ischemic semi-dark zone rescue rate than patients with poor collateral circulation.

Recommendation 6: Methods for achieving reperfusion in the acute phase of AIS include intravenous thrombolysis, EVT, and open collateral circulation
.
For non-recanalized patients, early opening of collateral circulation can increase ischemic perfusion and rescue ischemic semi-dark zones, which is one
of the main ways to improve the success rate of blood flow reperfusion in patients with AIS.

05 Significance of collateral circulation in AIS intravenous thrombolysis

Due to the short treatment window for AIS, timely assessment and rapid diagnosis are essential
.
The green channel for stroke treatment should be cleared in the emergency department, and thrombolysis should be actively performed in patients with indications for intravenous thrombolysis
.
For patients with an extended or uncertain thrombolysis window, vascular examination for collateral circulation assessment can be performed to help understand the pathogenesis and etiology of AIS and guide the selection of the correct treatment, but care should be taken to avoid delaying thrombolysis due to collateral circulation assessment and vascular examination
.

Collateral circulatory status is a major factor
in assessing the efficacy of intravenous thrombolytic therapy in patients with AIS.
Patients with good collateral circulation have a larger semi-dark zone and respond well
to intravenous thrombolytic therapy.
A retrospective cohort study showed that a good collateral circulation score was strongly associated with a moderate systolic blood pressure increase, aspects score, and a good neurological prognosis; In patients receiving intravenous thrombolysis, those with good collateral circulation have a better
prognosis.
A meta-analysis of 42 studies showed that patients with AIS with good collateral had better neurological performance at 3 and 6 months after thrombolysis, and good collateral circulation was strongly associated
with smaller infarct size at baseline, lower rates of intracranial haemorrhage, and higher rates of early neurological improvement.
IN ADDITION, COLLATERAL CIRCULATION MAY BE A VARIABLE TO CONSIDER BEFORE THROMBOLYSIS, AND A LOW ASPECTS SCORE IS OFTEN ASSOCIATED WITH EARLY LARGE-SCALE INFARCTION AND POOR NEUROLOGICAL PROGNOSIS, WHICH IS A RELATIVE CONTRAINDICATION TO VASCULAR RECANALIZATION
.

A study on the effect of collateral circulation on thrombolysis prognosis in patients with AIS showed that in patients with large-scale cerebral infarction who are not suitable for thrombolysis under the traditional definition, the presence of good collateral circulation was confirmed by the ASPECTS score, and the prognosis of patients after thrombolysis was significantly improved, which proved that collateral circulation assessment before thrombolysis was helpful for a more rational and scientific selection of thrombolysis patients
.

Recommendation 7: Collateral circulation status is closely related
to the prognosis of thrombolytic efficacy.
Collateral circulation assessment before thrombolysis in the overtime window helps emergency physicians to reasonably and scientifically select patients with thrombolysis, improve patient prognosis and reduce the occurrence
of complications.

06 Significance of collateral circulation in AIS recanalization

EVT is the first-line treatment for AIS caused by large vessel occlusion, and good collateral circulation is a good assessment of the efficacy of EVT
.
One study showed good collateral circulation and higher reperfusion rates, better prognosis
.
A single-center retrospective 2021 study of 626 patients with large-vessel occlusive AIS who underwent EVT was designed to assess whether good collateral blood flow improves the efficacy
of EVT.
Results showed that patients with good collateral blood flow achieved higher levels
of reperfusion with fewer EVT procedures.

The ischemic semi-dark zone is the basis and key to the benefits of EVT in AIS patients, and protecting the ischemic semi-dark zone can enable more patients to meet the inclusion criteria for vascular opening and improve clinical prognosis.
The collateral circulation status is the main determinant of
the ischemic semidark zone.
In AIS patients receiving EVT, better collateral status was found to be associated with better functional outcomes and greater treatment benefit, but not
with treatment time window.
Therefore, early assessment of the ischemic semi-dark zone through collateral circulation, without mechanically relying on the time window, and scientific and reasonable selection of patients for EVT can improve the success rate of treatment and reduce complications
.

A 2021 study found that EVT improved neurological prognosis in both clinical-image mismatch and perfusion-infarct mismatched groups; EVT is clearly beneficial
when there is a clinical-image mismatch in AIS patients with a time window of 6~24 h.

Recommendation 8: Collateral circulation has significant predictive value for prognosis in patients with AIS undergoing EVT, and the emergency physician should perform collateral circulation assessment
in patients who are to be treated to EVT.

07 Open collateral circulation drugs and non-drug treatments

7.
1 Open collateral circulation non-drug treatment

Nonpharmacologic interventions for open collateral circulation mainly include extracranial-intracranial artery bypass; external counterpulsation (ECP) and Neuroflflo technologies; Head down position ; Lower body positive pressure (LBPP).

(1) Extracranial-intracranial artery bypass surgery: only for patients with significant reduction in cerebral blood flow reserve, it can be used after careful evaluation of benefits and risks; It is not effective
in patients with AIS with intracranial large artery stenosis.
Studies have found that extracranial-intracranial bypass surgery plus medical therapy does not reduce the risk
of recurrence of ipsilateral ischaemic stroke after 2 years compared with medical therapy alone in patients with recent symptomatic atherosclerotic internal carotid artery occlusion.

(2) ECP and NeuroFlo technology: ECP is a non-invasive method to improve vital organ perfusion, which can increase diastolic blood flow and reduce systolic afterload, increase blood flow to the heart, brain and kidneys, and may benefit specific populations, but there is a lack of large randomized controlled trials to confirm.

ECP has been found to improve cerebral perfusion and collateral blood supply by increasing blood pressure and cerebral blood flow velocity in patients with AIS, and is associated with
a good prognosis of neurological function.
ECP provides patients with a safe way to increase cerebral blood flow, possibly with a potentially better therapeutic outcome
by optimizing hemodynamics.

The use of NeuroFlo catheter to partially block the aorta can increase cerebral perfusion, which is a new collateral treatment strategy, and studies have confirmed that NeuroFlo catheter therapy within 8~24 hours after the onset of symptoms in AIS patients is safe and feasible
.
In some specific populations, such as age greater than 70 years old, within 6 hours of onset, moderate neurological impairment (NIHSS score 8~14 points), the clinical effect is more significant
.

(3) Bowed head: Although lying flat and lowering the head position theoretically increases blood flow to the brain, a study of 11,093 patients with AIS showed that this approach is currently ineffective
.
The study interventions were flat and semi-recumbent, observing the degree of disability at day 90; Results showed no statistically significant
difference in the degree of disability after acute stroke between patients lying flat at 24 hours and sitting up with their heads raised at least 30° at 24 hours.

(4) LBPP: This method is easy to use and is a non-pharmacological non-invasive treatment
.
LBPP allows for rapid transfer of venous blood from the lower body to the upper body, thereby improving cardiac preload and output, and increasing cerebral blood flow and collateral circulation
.
Although retrospective studies have found that LBPP significantly improves blood flow velocity in symptomatic and asymptomatic middle cerebral arteries and basilar arteries, further randomized controlled trials are needed to determine
whether LBPP has long-term benefits for intracranial circulation.

Recommendation 9: Extracranial-intracranial artery bypass surgery is not recommended in patients with AIS with intracranial large artery stenosis; ECP, NeuroFlo therapy, and LBPP may only be effective in certain patients with AIS; The bowed cephalic position, although it increases cerebral blood flow, is not recommended in patients with
AIS.

7.
2 Open collateral circulation drug treatment

Pharmacological interventions mainly include statins, tetraphthalide, eureclin, and blood pressure control drugs
.

(1) Statins: are the first-line drugs for the treatment of AIS, and their use before and after AIS can reduce the mortality rate and improve long-term outcomes, especially for patients with non-cardiogenic AIS and atrial fibrillation cardiogenic stroke
.
In addition to lipid-lowering and plaque stabilization, its pleiotropic also plays an important role, including opening collateral circulation, promoting and inducing vascular endothelial nitric oxide synthesis and angiogenesis
.

One meta-analysis study confirmed that statin pretreatment may be associated
with improved collateral circulatory status, final infarct volume reduction, and improved neurological prognosis in patients with AIS.
Pre-stroke statin use has also been associated with good leptomeningeal collateral circulation and clinical prognosis in AIS patients with middle cerebral artery occlusion, but not with lower stroke severity (NIHSS score ≤ 14), and further research is needed to confirm this claim
.
In addition, statins promote the opening of posterior collateral circulation of EVT in patients with AIS
.
Prospective studies have shown that 20 mg of atorvastatin daily is safe and effective
for postoperative collateral circulation formation induced by superficial temporal artery vascular fusion.
In addition, studies have also found that ischemia-reperfusion injury and vascular reocclusion after EVT in patients with AIS lead to poor prognosis, and long-term statin use may prevent or reduce postoperative reperfusion injury and vascular reocclusion to protect neurological function
.

(2) Butylphthalide: Butyphthalide is a new chemical class I drug independently developed in China, which can promote the opening of collateral circulation, improve blood perfusion, and save the ischemic semi-dark zone
.
Multiple multicenter, randomized, double-blind clinical trials have demonstrated its safety and efficacy in the treatment of AIS and improved neurological function
in patients.
In addition, tetrabenzphthalide enhances the efficacy
of intravenous thrombolysis and EVT.
Studies have shown that buphthalide can slow the early neurological deterioration after intravenous thrombolysis in patients with AIS, and the early combination of buphthalide after EVT can significantly improve the prognosis of 90-day function in patients and reduce the rate of symptomatic intracranial hemorrhage and mortality
.

(3) Eureklin: It is a high-purity kininogenase isolated and refined from human urine, hydrolyzed kininogen in the body, selectively dilates microvessels in hypoxia and ischemic areas, and promotes the function of
vascular endothelium.
Studies have found that eureklin can reduce the mortality and disability rates of AIS and improve the neurological function
of patients by opening the collateral circulation.

(4) Control blood pressure: The vast majority of AIS patients have significantly increased blood pressure at the onset, excessive blood pressure will lead to excessive perfusion and intracranial pressure increase, especially thrombolysis patients blood pressure should be controlled at <180 110="" mmhg="" 1mmhg="0.
133">220 mmHg or diastolic blood pressure >120 mmHg, can control blood pressure, the average arterial pressure (MAP) within 1h decreases by 15%, but the systolic blood pressure is not less than 160mmHg
。 When AIS is accompanied by hypotension, it can lead to cerebral hypoperfusion, affecting the opening of collateral circulation and the existence of the ischemic semi-dark zone, so after endovascular thrombectomy in patients with AIS, appropriate increase in blood pressure (MAP >80 mmHg) is feasible or safe, helping to open collateral circulation and protect the ischemic semi-dark zone, and improve neurological function
in some patients.
Elevated blood pressure has been found to increase collateral cerebral blood flow and oxygenation, and to improve cerebral oxygen metabolism in
the core and penumbra.

A 2019 study showed that medication-induced hypertension was safe and improved early neurologic function and long-term functional independence
in non-cardiac stroke patients who were not candidates for intravenous thrombolysis or angioplasty or progression.
However, this intervention method has certain requirements for the enrolled population, and needs to be individualized according
to the patient's own situation.
Conversely, low blood pressure can also lead to adverse outcomes
.
A 2015 study found that hypotension during sedation negatively affected collateral circulation in patients with large vessel occlusive AIS after EVT, and subsequent vasopressor therapy may prevent collateral circulation from worsening and reduce the growth
of infarct area.

Recommendation 10: Pharmacological treatments to improve collateral circulation include statins, mephthalide and blood pressure
control.
Statins may improve cerebral perfusion in noncardiogenic AIS; Butylphthalide can promote the opening of collateral circulation, improve blood perfusion, rescue ischemic semi-dark zone, and improve nervous system function; Blood pressure control can be used as a noninvasive treatment
to improve collateral circulation in patients with AIS.

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