The determinants of collateral circulation status in patients with chronic cerebral arterial circle occlusion: A STROBE Study

Abstract

The condition of collateral pathways is an important predictor of stroke prognoses; however the major determinants of collaterals are still unknown. The purpose of this study is to identify potentially determinants for collateral circulation status in patients with chronic occlusion of cerebral arterial circle. All patients with chronic occlusion of either unilateral internal carotid artery or middle cerebral artery M1 or M2 segment, diagnosed by digital subtraction angiography at the neurology department of the First Medical Centre of Chinese PLA General Hospital from January 2015 to December 2017, were retrospectively collected in our sample. After screening according to inclusion and exclusion criteria, the patients’ relevant clinical data were collected and analyzed. Collateral circulations were assessed by 2 independent raters using the American society of interventional and therapeutic neuroradiology/society of interventional radiology flow-grading system. Baseline characteristics (n = 163): our sample consists of 116 (71.2%) male and 47 (28.8%) female patients with an average age of 57.5 ± 11.9 years. Cerebral collateral flow was poor in 59 (36.2%) patients. Our univariate analyses showed that poor collateral circulation was associated with lower high-density lipoproteins cholesterol (HDL), elevated homocysteine levels, aging and hyperlipidemia. A multivariate analysis identified HDL, homocysteine levels and ageing as major predictors for collateral circulation status. In the subgroup analysis, the HDL contributed to collateral angiogenesis internal carotid artery occlusion group. In the middle cerebral artery occlusion group, the homocysteine and ageing were related to the poor collateral status. Low HDL, high levels of homocysteine and ageing are identified as possible risk factors for a poor collateral vessel blood flow in patients with chronic anterior circulation occlusion.

Large differences in collateral blood vessel abundance among individuals arise from multiple genetic variants

“…Pre-procedural scores for collateral blood flow in patients with acute large-vessel ischemic stroke show a similar distribution. [1][2][3][4][5][6] This congruence suggests that genetic background-dependent differences in collateral abundance are a primary contributor to variation in stroke severity in humans. That is, while cardiovascular-stroke risk factors, eg aging, hypertension, diabetes and other co-morbidities cause a small but significant amount of rarefaction of collateral number and diameter, 15,51 and references therein genetic differences, such as examined herein, play a much greater role in the magnitude of variation in collateral abundance among individuals.…”

“…[1][2][3][4][5][6][7][8][9][10] For example, the level of flow mediated by the brain's pial (leptomeningeal) collateral network, which can be estimated (ie, scored) in patients presenting with acute occlusion of the proximal middle cerebral artery (MCA)-the most common cause of ischemic stroke-partitions into $25% with low, $50% intermediate, and $25% high collateral flow, with the rate of progression and severity of subsequent ischemic injury following accordingly. [1][2][3][4][5][6] Pre-treatment collateral score also correlates directly with the efficacy of thrombolysis, thrombectomy, and extension of the therapeutic time window for revascularization, and inversely with the risk for hemorrhagic transformation after treatment. [1][2][3][4][5][6] The mechanisms responsible for this large variation, which extends to the collateral network in other tissues of the same individual, [11][12][13][14][15][16][17][18][19] are not well understood and have become an area of increasing interest.…”

“…[1][2][3][4][5][6] Pre-treatment collateral score also correlates directly with the efficacy of thrombolysis, thrombectomy, and extension of the therapeutic time window for revascularization, and inversely with the risk for hemorrhagic transformation after treatment. [1][2][3][4][5][6] The mechanisms responsible for this large variation, which extends to the collateral network in other tissues of the same individual, [11][12][13][14][15][16][17][18][19] are not well understood and have become an area of increasing interest.…”

“…However, the aggregate amount of blood flow that they provide, which can be assessed following pathologic or diagnostic occlusion of a major artery supplying the tissue, exhibits wide variation among individuals. [1][2][3][4][5][6][7][8][9][10] For example, the level of flow mediated by the brain's pial (leptomeningeal) collateral network, which can be estimated (ie, scored) in patients presenting with acute occlusion of the proximal middle cerebral artery (MCA)-the most common cause of ischemic stroke-partitions into $25% with low, $50% intermediate, and $25% high collateral flow, with the rate of progression and severity of subsequent ischemic injury following accordingly. [1][2][3][4][5][6] Pre-treatment collateral score also correlates directly with the efficacy of thrombolysis, thrombectomy, and extension of the therapeutic time window for revascularization, and inversely with the risk for hemorrhagic transformation after treatment.…”

Collateral Flow: Prolonging the Ischemic Penumbra

“…Polymorphisms in the Rabep2 gene have been demonstrated to influence collateral extent and the severity of resultant stroke in mice [15]. Preliminary studies have begun to address biologic influences in humans, but much more work is still needed [16]. Large collaborative groups have begun to address the genetic architecture of collaterals and other acute stroke traits in humans [17].…”