Evaluation of cortical venous drainage in patients with Acute Ischemic Stroke

 But nothing here solves the problems of cerebral edema, reperfusion injury or Capillaries that don't open due to pericytes

Our incompetent stroke medical 'professionals' should be demanding solutions to these problems instead of just fucking lazy descriptions!

Evaluation of cortical venous drainage in patients with Acute Ischemic Stroke

Runyang Li^1†Xi Li^2†Jie Li^3†Xinjun Dai³Junhong Guo^1*Shaoshuai Wang^1*

• ¹Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, China
• ²Department of Nephrology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China
• ³Department of Oncology and Hematology, Liuyang Hospital of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China

The emergence of Mechanical thrombectomy (MT) has changed the treatment modalities for Acute Ischemic Stroke (AIS). But still 45 to 55% of patients cannot achieve functional independence after sufficient recanalization through endovascular treatment, defined as “futile reperfusion.” Poor collateral circulation and microcirculation are key factors affecting prognosis. In the past, the assessment of these mainly focused on intracranial arteries and their collateral, neglecting the important role of the venous system in acute brain injury. More and more studies have found that “poor venous drainage” is associated with poor prognosis. However, there is currently no unified standard for the assessment of “cortical venous drainage.” This paper reviews the pathophysiology of the relationship between “cortical venous drainage” and prognosis, as well as the assessment methods and indicators of “cortical venous drainage,” aiming to provide a strong basis for the preoperative assessment of AIS patients and the selection of treatment plans.

Introduction

In clinical practice, it has been found that even up to half of the AIS patients still cannot achieve functional independence after MT (Consoli et al., 2023). “Collateral circulation and microcirculation” are considered to be the key factors affecting the prognosis of MT (Wang et al., 2023; Li et al., 2024). Good “collateral circulation and microcirculatory” can improve the prognosis of patients by reducing the core infarct volume and lowering the risk of postoperative hemorrhagic transformation (Li et al., 2024). “Venous drainage” (or venous outflow) is an evaluation of the downstream of microcirculation and the final outlet of cerebral blood circulation, and controls the local perfusion in the downstream area (Li et al., 2024), and good “venous drainage” reflects that blood flows unobstructed through brain tissue and is regarded as a powerful predictor of good micro-perfusion in brain tissue (Faizy et al., 2022). Multiple studies (Li et al., 2024; Faizy et al., 2022; Faizy et al., 2021a,b; Dai et al., 2024; Salim et al., 2025) have found that patients with “good venous drainage “have a better prognosis after MT treatment, therefore, for maintaining good perfusion of brain tissue, downstream venous outflow is as important as upstream arterial perfusion (Dai et al., 2024). The “cortical vein” covers the surface of the cerebral cortex like a network. It is a superficial part of the cerebral venous system and is mainly responsible for draining the blood of the cerebral cortex. Since the internal carotid artery system provides blood to the anterior 2/3 of the brain, the venous blood in this area is mainly drained through the cortical vein. Therefore, cortical venous drainage has a unique advantage in evaluating the collateral circulation in the anterior circulation blood supply area. Currently, the evaluation of cortical venous drainage is mostly based on imaging results, but the imaging techniques and indicators used in various evaluation methods are varied. This article conducts a detailed review of the pathophysiological mechanisms linking venous drainage to acute brain injury. Additionally, it elaborates on the assessment protocols for venous drainage that are established based on diverse imaging modalities. To further illustrate the discussed concepts, a selection of clinical cases is also presented in this article.

Pathophysiology of cortical venous drainage and poor prognosis in acute ischemic stroke

Under normal circumstances, cerebral autoregulation matches the amount of blood entering the brain from the arterial system with that flowing out of the brain through the venous system. This prevents the brain from damage caused by hypoperfusion or hyperperfusion, keeping the total blood flow in the brain constant (Dai et al., 2024; Chen et al., 2015).

After acute stroke, the brain tissue in the infarcted area becomes edematous. The swollen end-feet of astrocytes can compress the thin walls of venules and capillaries, and even cause blood vessel occlusion. Due to the lack of a smooth muscle cell layer, the venous system is more prone to tissue edema and pressure elevation compared to the arterial system. The elevated cerebral venous pressure not only increases the exudate in the perivascular space but also leads to the disruption of the blood-brain barrier, increasing its permeability and further exacerbating cerebral edema (Chen et al., 2015). Clinically, in patients with a large core infarct volume, the occurrence of severe cerebral edema after thrombectomy may cause midline shift, affecting the prognosis (Nie et al., 2023).

Restoring blood supply to temporarily ischemic brain tissue may cause damage to the tissue bed, namely “ischemic reperfusion injury” (Nie et al., 2023). After acute brain tissue injury occurs, cerebral edema leads to an increase in intracranial pressure. This pressure compresses veins, obstructs venous outflow, causes local blood stasis, affects the blood supply to brain tissue and the excretion of metabolic products, resulting in the accumulation of metabolic waste and the generation of harmful free radicals. The subsequent inflammatory response and oxidative stress will exacerbate reperfusion injury (Salim et al., 2025; Nie et al., 2023). Abnormal “venous outflow” such as that of the superficial middle cerebral vein (SMCV) affects the blood supply and metabolism of tissues, aggravating tissue damage. This indirectly demonstrates the association between venous drainage disorders and reperfusion injury (Dai et al., 2024). On the other hand, when there is a mismatch between “decreased venous outflow” and “increased arterial blood flow” after blood vessel recanalization, venous pressure will rise. Venous hypertension may cause the rupture of fragile thin-walled cortical veins, leading to secondary cerebral hemorrhage, that is, “hemorrhagic transformation”.

Currently, it is believed that for clinical outcomes, tissue reperfusion is more important than arterial recanalization, although angiography shows complete recanalization, persistent tissue hypoperfusion due to incomplete microcirculation reperfusion (the “no-reflow”) can still lead to poor prognosis (Ng et al., 2022; Zaidat et al., 2013). The hypoperfusion mechanism in the “no-reflow” phenomenon is mainly due to pericyte contraction, endothelial cell swelling, lumen blockage by white blood cells and microthrombi, as well as damage to blood vessels caused by thrombectomy itself, resulting in impaired capillary bed perfusion (Ng et al., 2022; Pasarikovski et al., 2020).

When arterial collateral blood flow is interrupted due to factors such as edema, microthrombi, and vasospasm, resulting in poor perfusion of ischemic tissue, a decrease in venous outflow will further exacerbate brain tissue edema in this area. At the same time, tissue edema increases interstitial pressure, further raising the resistance of the venous drainage system. This affects the normal return of blood, causing poor excretion of metabolic products in brain tissue and ultimately aggravating the damage to brain tissue (Dai et al., 2024; Chen et al., 2015).

Assessment of cortical venous drainage based on different imaging tools

Computed tomography angiography

The Cortical venous opacification evaluation score (COVES) based on computed tomography angiography (CTA) is the most commonly used evaluation scheme at present. COVES selects three representative venous outflow networks, namely the Superficial middle cerebral vein (SMCA), Vein of Labbe (VOL), and Sphenoparietal sinus (SPS), which can basically cover the venous drainage of the entire MCA region. This means that COVES can comprehensively delineate the venous blood return in the MCA region and has lower anatomical variability compared with other cortical veins, making it more convenient and accurate when conducting comparisons among different individuals (Jansen et al., 2018; Kiliç and Akakin, 2008). In addition, since CTA can clearly display the vascular structure, it provides a good image basis for COVES, especially single-phase CTA, and its wide availability in clinical practice enables COVES to conduct evaluations more conveniently based on these high-quality CTA images.

The filling of each vein was graded by baseline CTA (Jansen et al., 2018) (Table 1, Figure 1). Patients with COVES>0 had a higher probability of good prognosis (mRS 0–2) (OR = 3.0; 95%CI:1.7, 5.4) (Faizy et al., 2022), however, there is still controversy regarding the optimal cut-off value for the COVES. In a multicenter retrospective study involving 649 patients, Faizy Tobias calculated the optimal cutoff value of COVES by ROC curve as 2.5 (area under curve 0.75; sensitivity 60%; specificity 79%) (Faizy et al., 2021a,b). In their study, COVES score of 0–2 was considered to indicate poor venous outflow, and COVES score of 3–6 was considered to indicate good venous outflow. And they also adopted this conclusion in another multicenter study involving 647 patients (Jansen et al., 2018). However, a study conducted by Gong et al. (2024) included a total of 332 patients, all of whom were large vessel occlusion patients receiving endovascular therapy in the late window period. Through marginal effect analysis, this study found that the probabilities of having a favorable prognosis (mRS: 0–2) and an unfavorable prognosis (mRS: > 2) intersected at a score of four. Patients with a COVES score ≥ 4 had a significantly higher probability of achieving a favorable prognosis than those with a COVES score < 4, suggesting that a COVES score of 4 might be the cut-off point for distinguishing a better prognosis.

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