Cerebral Circulation Time Is a Potential Predictor of Disabling Ischemic Cerebrovascular Events in Patients With Non-disabling Middle Cerebral Artery Stenosis

Patients with non-disabling middle cerebral artery (MCA) stenosis (ND-MCAS) are at risk for disabling ischemic cerebrovascular events (DICE) despite aggressive medical therapy. In this study, we aimed to verify whether cerebral circulation time (CCT) was a potential predictor of DICE in patients with ND-MCAS. From January 2015 to January 2020, 46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography (DSA) in this convenience sampling study. They were divided into the DICE (–) and DICE (+) groups based on the occurrence of DICE within 3 months after DSA. The CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein during DSA. The rCCT (relative CCT) was defined as the ratio of the CCT of the stenotic side (sCCT) to the CCT of the healthy side (hCCT). The differences in sCCT, hCCT, and rCCT between the two groups were analyzed with Mann-Whitney U tests. Logistic regression analysis was performed to evaluate the association between the risk factors and DICE. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of rCCT in identifying DICE in ND-MCAS patients. The results showed that DICE appeared in 5 of the 46 patients within 3 months. rCCT were significantly increased in the DICE (+) group compared with the DICE (–) group [1.08 (1.05, 1.14) vs. 1.30 (1.22, 1.54), p < 0.001]. Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE (odds ratio = 1.273, p = 0.019) after adjustment for potential confounders (age, diabetes, antithrombotic use, and stenosis degree). ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE (+) group from the DICE (–) group among ND-MCAS patients (area under the curve = 0.985, p < 0.001), with an optimal cutoff point of 1.20 (100% sensitivity, 97.6% specificity). In conclusion, prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify individuals at risk of DICE.

Insights into Endothelin-3 and Multiple Sclerosis

Endothelins are powerful vasoconstrictor peptides that play numerous other roles. Endothelin-1 (ET1) is the principal isoform produced by the endothelium in the human cardiovascular system. Endothelin-3 (ET3) and its rPptor affinity have been demonstrated to support neuronal repair mechanisms throughout life. In multiple sclerosis (MS), the role of vasoactive peptides are not well defined. Here we focus on ET3, specifically the plasma levels between MS patients and healthy subjects. Furthermore, we evaluated the changes in ET1 and ET3 plasma levels during different disease phases, the correlation between ET3 and cerebral circulation time, and the relationship between ET1 and ET3. In MS patients, the ET3 plasma levels were altered in a time-dependent manner. These results could support a putative role of ET3 in neuroprotection and/or neuroimmune modulation over time.

Prediction of hyperperfusion phenomenon after carotid artery stenting and carotid angioplasty using quantitative DSA with cerebral circulation time imaging

BackgroundHyperperfusion syndrome after carotid interventions has a low incidence but it can lead to morbidity and mortality.ObjectiveTo evaluate the usefulness of quantitative DSA for predicting hyperperfusion phenomenon (HPP) after carotid artery stenting and angioplasty.MethodsThirty-three consecutive patients with carotid stenosis treated with carotid artery stenting or angioplasty between February 2014 and August 2016 were included. Color-coded digital subtraction angiograms showing the time to maximum contrast intensity of each image pixel were obtained from conventional DSA before and after procedures. The cerebral circulation time (CCT) was defined as the difference in the relative time to maximum intensity between arterial and venous regions of interest set on the angiograms. HPP was diagnosed straight after the procedure with qualitative 123I-IMP single-photon emission CT (SPECT). Cut-off points for detecting HPP for preprocedural CCT and periprocedural change of CCT were assessed by receiver operating characteristic analysis using 123I-IMP SPECT as reference standard.Results123I-IMP SPECT showed HPP in 4 of 33 patients. In these 4 patients, preprocedural prolongation of CCT (13.0±6.1 vs 7.2±1.3 s; p<0.001) was seen compared with patients without HPP as well as larger periprocedural changes of CCT (5.9±5.7 vs 0.5±1.3 s; p<0.001). The optimal cut-off points of preprocedural CCT and change of CCT for predicting HPP were 8.0 s (100% sensitivity, 69% specificity) and 3.2 s (75% sensitivity, 100% specificity), respectively.ConclusionsPreprocedural prolongation and greater periprocedural change of CCT are associated with the occurrence of HPP. Periprocedural evaluation of CCT may be useful for predicting HPP.

Prolonged cerebral circulation time is more associated with symptomatic carotid stenosis than stenosis degree or collateral circulation

Background and purposeCurrent practice of revascularization for carotid stenosis (CS) primarily relies on symptoms and degree of stenosis. Other parameters, such as collateral circulation and cerebral circulation time (CCT), might influence the stroke risk in CS. This study was conducted to (1) investigate whether CCT is more associated with symptomatic CS than degree of stenosis and (2) elucidate the associations among the degree of stenosis, collateral status, and CCT.MethodsFrom 2010 to 2016, 82 patients with unilateral CS were enrolled for DSA and divided into symptomatic and asymptomatic groups based on clinical presentation. CCT was defined as the difference between the time taken by the cavernous internal carotid artery and parietal vein to reach the maximal contrast medium intensities on lateral DSA. The degree of stenosis, collateral status, and CCT of the two groups were compared. Logistic regression analysis was performed to estimate the OR for symptomatic CS with the imaging variables.ResultsThe symptomatic group had a significantly higher degree of stenosis and longer CCT. CCT (OR 1.95, p=0.013) was more associated with symptomatic CS than the degree of stenosis (OR 1.03, p=0.229), after adjustment for potential confounders—namely, age, sex, antithrombotic use, and collateral status. Symptomatic high grade CS with collaterals had a non-significantly shorter CCT than those without collaterals.ConclusionsDSA derived CCT is more reflective of the hemodynamic differences between symptomatic and asymptomatic CS than degree of stenosis. Collaterals may not effectively reduce CCT in symptomatic high grade CS.

Influence of Circulating Endothelin-1 and Asymmetric Dimethylarginine on Whole Brain Circulation Time in Multiple Sclerosis

Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay. Lesion load (LL) and brain volume (BV) were obtained by magnetic resonance imaging. Cerebral circulation time was correlated to ET1, ADMA, LL, BV, disease duration (DD), and Expanded Disability Status Scale (EDSS). In MS, both ET1 and ADMA were significantly higher than C ( P < .0001); CCT was approximately 2 times lower than C ( P < .0001) and significantly slower in SP than in RR-MS ( P = .0215). Cerebral circulation time significantly correlated with ET1 in SP-MS ( r = 0.38), whereas in RR-MS CCT significantly correlated with DD ( r = 0.75). The LL, BV, and EDSS did not correlate with CCT. Endothelin-1 significantly influences CCT delay in SP-MS. Diversely, CCT in RR-MS is independent of ET1 and correlates significantly with DD. We conclude that in RR-MS, DD responds to neurovascular damage accumulation. It is supposed that high ET1 and ADMA levels stem from a protective response to early insults, aimed at opposing nitric oxide overproduction, whereas persistent pathological ET1 and ADMA levels translate into detrimental long-term effects, due to increased brain micro-vessel resistance.