In a cohort of patients who underwent head and neck CT angiography for acute ischemic stroke due to internal carotid artery terminus/middle cerebral artery M1 occlusion, while they have moderate or greater ipsilateral internal carotid artery stenosis, we found that AIS patients with ipsilateral PCFS will have a higher rate of core growth and relatively poorer collateral circulation than those without imaging suggestive of PCFS. When comparing the PCAT density changes between the two groups, it is obviously that PCFS group trends to show increased attenuation more significantly. Additionally, PCFS was found to be significantly related to a poor prognosis, including delirium, drowsiness, herniation of brain and severe neurological dysfunction of the limbs affecting the quality of daily life.
Given recent studies supporting the role of the PCAT attenuation increased as a helpful radiographic indication for localized inflammation, we have found that the degree of PCATattenuation is significantly correlated with the severity degree of local adipose inflammation in previous study [10]. Our data in this study suggests that AIS patients accompanying with ipsilateral PCFS are inclined to have acute inflammatory exudation of the carotid artery adipose tissue, which is likely more severer than the relatively mild, focal chronic fat tissue inflammation. The inflammatory adipose tissue became dysfunctional gradually, which is characterized by infiltration of inflammatory cells and aberrant production of adipokines [11]. Several adipokines such as lipocalin [11] and adipocyte fatty acid binding protein (A-FABP) [12] are identified to mediate the cross talk between adipose tissue and cardiovascular and cerebrovascular system. A-FABP has been elucidated to play an important role in dysfunctional PCAT associated inflammatory and correlate with carotid atherosclerosis, plaque vulnerability [11]. Elevated circulating level of A-FABP in patients with carotid atherosclerosis can causes cerebral embolization and acute ischemic stroke and relate positively with infarct volume and poor clinical outcomes. Boya Liao et al. [6] reported that circulating and cerebral A-FABP were increased in mice after acute ischemic stroke and cerebral ischaemic injury in mice were ameliorated after genetic ablation of A-FABP. These data from genetic ablation and pharmacological inhibition in mice supported that A-FABP is involved in the progress of acute ischemic stroke. In their study, A-FABP was identified as a novel factor that regulate the Blood-brain barrier disruption after acute ischemic stroke and exacerbate symptoms of cerebral ischemia and we speculate that it may be related to the core growth rate of AIS patients with ipsilateral PCFS.
We further found a negative correlation between the grade of collateral status and infarct core volume, CGR. It implies AIS patients with poor collateral status may probably have large infarct core volume and faster CGR. Collateral status has been reported [13] to play an important role in the infarct core volume. Good collateral flow, which ustains brain viability distal to arterial occlusion, correlates with small ischemic core volume [14–17]. Campbell BC et al. [18] correlated leptomeningeal collateral flow with simultaneous assessment of perfusion parameters using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, highlighting the importance of collateral flow as a key determinant of infract evolution and reporting the association of the existence of fluctuations in collateral flow over time with ischemic core growth. Similarly, Longting Lin et al. [7] have validated that collateral status is a major determinant for core growth. These findings are relevant for clinical practice because CTA is more widely available in the emergency setting than MR imaging examination.
Our study showed that there was a weak negative correlation between the grade of collateral status and PCFS, while the relationship between PCFS and intracranial collateral circulation has not been confirmed by relevant studies at present. We speculate that this may be because atherosclerosis is a chronic disease that affects arteries throughout the whole-body, and the chronic inflammation of the vessel wall affects the regeneration of terminal vascular branches.
In addition, our study showed PCFS correlates with larger ischemic core volume and CGR. The frequency of adverse prognosis was greater in cases with PCFS (83.33%,10 of 12 cases) than in control subjects (19.11%,13 of 68 cases). The prevalence of occlusive diseases was higher in patients with PCFS than that in the control group, which revealed the PCFS is a meaningful CT finding of acute carotid atherosclerotic lesion and alert the doctors to a critically stroke patient or a probably poor-prognosis. According to previous studies [19, 20], CGR was demonstrated to have large variability within 24 hours after onset and may continue to grow for up to 72 hours after stroke without any treatment to restore the blood supply, he ischemic core may grow into the whole ischemic region and result in a diminishing of the penumbra. GR has demonstrated [21] an independent predictor of adverse outcome, which is not only a biomarker of large infraction but also an assessment of the ongoing ischemic process.
Rupture of high-risk plaques is the major contributing etiology of acute stroke. The pathophysiology of atherosclerotic plaque or atherosclerotic tumor is the increase of microemboli or macroemboli, thrombus or platelet emboli in situ. Thrombi often originates at the internal carotid artery stump and embolize to downstream circulation, thus causing symptoms of acute cerebral ischemia. Saba et al. [22] proposed that the degree of plaque enhancement is positively correlated with the increase of pericarotid adipose tissue density (PFD), which can be an indirect marker of plaque stability. In addition, high-risk plaques tend to rupture are generally large with a lipid-rich necrotic core, neovascularity (contrast plaque enhancement), intraplaque hemorrhage and inflammatory cell infiltration [23–25]. Recently, researchers [26] have verified the correlation between carotid intraplaque hemorrhage (IPH) and increased attenuation of PVAT. IPH is caused by damaged neovascularization in plaques due to vascular inflammation and oxidative stress, suggesting that PCATinflammation may play a crucial role in IPH. However, the differences between two groups in plaque area, plaque burden and lumen stenosis were not statistic significantly. In the cases we included in this study, the plaques at the carotid bifurcation caused moderate degree or severe carotid stenosis and were all classified as high-risk plaque, and our small sample size study was not able to achieve statistically significant results.
One patient with carotid artery dissection was excluded from consideration for inclusion, although he had significant PCFS. Carotid artery dissection is one of the causes of acute carotid occlusion, but our study focused on acute ischemic stroke patients with carotid atherosclerosis.
The retrospective study is limited by its single-center design and small sample size, and there is inevitable selection bias; thus, these findings are preliminary and need larger studies to confirm. We were unable to quantitative analysis of the levels of fatty acid binding proteins in the patients and could not assess their association with PCFS because of its a retrospective study. More importantly, application of this study is currently limited to patients with large vessel occlusions on ICA/MCA.