Effects of intracranial artery stenosis of anterior circulation on cognition-A CT perfusion-based study.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most important independent risk factors for stroke that is closely related to the occurrence of cognitive impairment. The relationship between ICAS and vascular cognitive impairment (VCI) remains unclear. Cerebral hemodynamic changes are one of the main causes of cognitive impairment. Computed tomographic perfusion (CTP) imaging can quantitatively analyze cerebral blood perfusion and quantify cerebral hemodynamic changes. Previous research on the relationship between hypoperfusion induced by ICAS and cognitive impairment, as well as its underlying mechanisms, remains relatively insufficient. This study is dedicated to elucidating the characteristics and potential mechanisms of cognitive impairment in ICAS patients with abnormal perfusion, utilizing CTP imaging as our primary investigative tool. METHODS: This study recruited 82 patients who suffer from non-disabling ischemic stroke (IS group) and 28 healthy controls. All participants underwent comprehensive neuropsychological assessments both collectively and individually, in addition to CTP imaging. Within the patient group, we further categorized individuals into two subgroups: the ischemic penumbra group (IP, N = 28) and the benign oligemia group (BO, N = 54), based on CTP parameters-Tmax. The correlations between cognitive function and abnormal perfusion were explored. RESULTS: The cognitive function, including the overall cognitive, memory, attention, executive functions, and language, was significantly impaired in the IS group compared with that in the control group. Further, there are statistical differences in the stroop color-word test-dot (Stroop-D) and Montreal Cognitive Assessment (MoCA) sub-items (memory + language) between the BO and IP groups. In the BO group, the score of Stroop-D is lower, and the MoCA sub-items are higher than the IP group. There is no correlation between CTP parameters and cognitive function. CONCLUSION: Cognitive function is significantly impaired in patients with ICAS, which is related to cerebral perfusion. Executive, memory, and language function were better preserved in ICAS patients without IP. Hence, this study posits that managing hypoperfusion induced by ICAS may play a pivotal role in the development of VCI.

Hemodynamic Impairment of Blood Pressure and Stroke Mechanisms in Symptomatic Intracranial Atherosclerotic Stenosis.

BACKGROUND: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment. METHODS: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018. The major exposures were translesional systolic blood pressure (SBP) drop and poststenotic mean arterial pressure (MAP), and the major study outcomes were cortex-involved infarcts and borderzone-involved infarcts, respectively. Multivariate logistic regression models and the bootstrap resampling method were utilized, adjusting for demographics and medical histories. RESULTS: In all, 184 (54.3%) cortex-involved infarcts and 70 (20.6%) borderzone-involved infarcts were identified. In multivariate logistic model, the upper quartile of SBP drop correlated with increased cortex-involved infarcts (odds ratio, 1.92 [95% CI, 1.03-3.57]; bootstrap analysis odds ratio, 2.07 [95% CI, 1.09-3.93]), and the lower quartile of poststenotic MAP may correlate with increased borderzone-involved infarcts (odds ratio, 2.07 [95% CI, 0.95-4.51]; bootstrap analysis odds ratio, 2.38 [95% CI, 1.04-5.45]). Restricted cubic spline analysis revealed a consistent upward trajectory of the relationship between translesional SBP drop and cortex-involved infarcts, while a downward trajectory between poststenotic MAP and borderzone-involved infarcts. SBP drop correlated with poststenotic MAP negatively (rs=-0.765; P<0.001). In generating hemodynamic impairment, simulating blood pressure modifications suggested that ensuring adequate blood pressure to maintain sufficient poststenotic MAP appears preferable to the reverse approach, due to the prolonged plateau period in the association between the translesional SBP drop and cortex-involved infarcts and the relatively short plateau period characterizing the correlation between poststenotic MAP and borderzone-involved infarcts. CONCLUSIONS: This research elucidates the role of hemodynamic impairment of blood pressure in symptomatic intracranial atherosclerotic stenosis-related stroke mechanisms, underscoring the necessity to conduct hemodynamic assessments when managing blood pressure in symptomatic intracranial atherosclerotic stenosis.

The guardian of intracranial vessels: Why the pericyte?

Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused by plaque formation. This condition leads to reduced blood flow to the brain, resulting in cerebral ischemia and hypoxia. Ischemic stroke (IS) resulting from ICAS poses a significant global public health challenge, especially among East Asian populations. However, the underlying causes of the notable variations in prevalence among diverse populations, as well as the most effective strategies for preventing and treating the rupture and blockage of intracranial plaques, remain incompletely comprehended. Rupture of plaques, bleeding, and thrombosis serve as precipitating factors in the pathogenesis of luminal obstruction in intracranial arteries. Pericytes play a crucial role in the structure and function of blood vessels and face significant challenges in regulating the Vasa Vasorum (VV)and preventing intraplaque hemorrhage (IPH). This review aims to explore innovative therapeutic strategies that target the pathophysiological mechanisms of vulnerable plaques by modulating pericyte biological function. It also discusses the potential applications of pericytes in central nervous system (CNS) diseases and their prospects as a therapeutic intervention in the field of biological tissue engineering regeneration.

Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

Hemodynamic Impairments of Evaluating Symptomatic Intracranial Atherosclerotic Stenosis using Quantitative Flow Ratio on Digital Subtraction Angiography : A Comparison with Computed Tomography Perfusion, MRI and Fractional Flow Reserve.

PURPOSE: Cerebral hemodynamics are important for the management of intracranial atherosclerotic stenosis (ICAS). The quantitative flow ratio (QFR) is a novel angiography-derived index for assessing the functional relevance of ICAS without pressure wires and adenosine. Good diagnostic yield with the hyperemic fractional flow reserve (FFR) have been reported, while data on the comparison of QFR to FFR are scarce. METHODS: In this prospective study 56 patients with anterior circulation symptomatic ICAS who received endovascular treatment were included. The new method of computing QFR from a single angiographic view, i.e., the Murray law-based QFR (µQFR), was applied to the examined vessels. An artificial intelligence algorithm was developed to realize the automatic delineation of vascular contour. Pressure gradients were measured before and after treatment within the lesion vessel using a pressure guidewire and the FFR was calculated. RESULTS: There was a good correlation between µQFR and FFR. Preoperative FFR predicted DWI watershed infarction (FFR optimal cut-off level: 0.755). Preoperative µQFR predicted DWI watershed infarction (µQFR optimal cut-off level: 0.51). Preoperative FFR predicted CTP hypoperfusion (FFR best predictive value: 0.62). Preoperative µQFR predicted CTP hypoperfusion (µQFR best predictive value: 0.375). CONCLUSION: The µQFR based on DSA images can be used as an indicator to assess the functional status of the lesion in patients with ICAS.

Computational Fluid Dynamics in Intracranial Atherosclerosis - Lessons from Cardiology: A Review of CFD in Intracranial Atherosclerosis.

BACKGROUND: Intracranial atherosclerosis is a common cause of stroke with a high recurrence rate. Haemodynamically significant lesions are associated with a particularly high risk of recurrence. Computational fluid dynamics (CFD) is a tool that has been investigated to identify haemodynamically significant lesions. CFD in the intracranial vasculature benefits from the precedent set by cardiology, where CFD is an established clinical tool. This precedent is particularly important in CFD as models are very heterogenous. There are many decisions-points in the model-creation process, usually involving a trade-off between computational expense and accuracy. OBJECTIVES: This study aimed to review published CFD models in intracranial atherosclerosis and compare them to those used in cardiology. METHODS: A systematic search for all published computational fluid dynamics models applied to intracranial atherosclerosis was performed. Each study was analysed as regards to the different steps in creating a fluid dynamics model and findings were compared with established cardiology CFD models. RESULTS AND CONCLUSION: 38 papers were screened and 12 were included in the final analysis. There were important differences between coronary and intracranial atherosclerosis models in the following areas: area of interest segmented, use of transient models vs steady-state models, boundary conditions, methods for solving the fluid dynamics equations and validation. These differences may be high-yield areas to explore for future research.

Risk Factors Control and Early Recurrent Cerebral Infarction in Patients with Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND: The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD. METHODS: We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event. RESULTS: Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01). CONCLUSIONS: Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD.

Outcomes of Rescue Endovascular Treatment of Emergent Large Vessel Occlusion in Patients With Underlying Intracranial Atherosclerosis: Insights From STAR.

Background Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO. Methods and Results We queried the databases of 10 thrombectomy-capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS-related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke Scale, Alberta Stroke Program Early CT Score, onset to groin puncture time, occlusion site, and final recanalization. Out of 3025 patients with MT, 182 (6%) patients required RT because of underlying ICAS. Balloon angioplasty was performed on 122 patients, and 117 patients had intracranial stenting. In the matched analysis, 141 patients who received RT matched to a similar number of controls. The number of thrombectomy passes was higher (3 versus 1, P<0.001), and procedural time was longer in the RT group (52 minutes versus 36 minutes, P=0.004). There was a higher rate of symptomatic hemorrhagic transformation in the RT group (7.8% versus 4.3%, P=0.211), however, the difference was not significant. There was no difference in 90-day modified Rankin scale of 0 to 2 (44% versus 47.5%, P=0.543) between patients in the RT and control groups. Conclusions In patients with ELVO with underlying ICAS requiring RT, despite longer procedure time and a more thrombectomy passes, the 90 days favorable outcomes were comparable with patients with embolic ELVO.

Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND AND PURPOSE: While prior studies identified risk factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease, few have assessed risk factors for early infarct recurrence. METHODS: We performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of intracranial atherosclerotic disease patients with recent (<21 days) stroke/transient ischemic attack, 50% to 99% stenosis and who underwent 6- to 8-week magnetic resonance imaging (MRI) per protocol. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6 to 8 weeks compared to index brain MRI. Qualifying events and clinical and imaging outcomes were centrally ascertained by 2 independent reviewers. We assessed the association between baseline clinical and imaging variables and recurrent infarct in bivariate models and multivariable logistic regression to identify independent predictors of infarct recurrence. RESULTS: Of 105 enrolled patients in MYRIAD, 89 (84.8%) were included in this analysis (mean age, 64±12 years, 54 [60.7%] were male, and 53 [59.6%] were White). The median time from qualifying event to MRI was 51+16 days, on which 22 (24.7%) patients had new or recurrent infarcts. Younger age (57.7 versus 66.0 years; P<0.01), diabetes (32.6% versus 14.6%, P=0.05), index stroke (31.3% versus 4.6%, P=0.01), anterior circulation location of stenosis (29.7% versus 12.0%, P=0.08), number of diffusion-weighted imaging lesions (>1: 40.0%, 1: 26.9% versus 0: 4.4%, P<0.01), and borderzone infarct pattern (63.6% versus 25.0%, P=0.01) on baseline MRI were associated with new or recurrent infarcts. Age (adjusted odds ratio, 0.93 [95% CI, 0.89-0.98], P<0.01) and number of diffusion-weighted imaging lesions (adjusted odds ratio, 3.24 [95% CI, 1.36-7.71], P<0.01) were independently associated with recurrent infarct adjusting for hypertension, diabetes, and stenosis location (anterior versus posterior circulation). CONCLUSIONS: An index multi-infarct pattern is associated with early recurrent infarcts, a finding that might be explained by plaque instability and artery-to-artery embolism. Further investigation of plaque vulnerability in intracranial atherosclerotic disease is needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02121028.

Revisiting the Evidence for Dipyridamole in Reducing Restenosis: A Systematic Review and Meta-analysis.

ABSTRACT: Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization.

Association of Plaque Features with Infarct Patterns in Patients with Acutely Symptomatic Middle Cerebral Artery Atherosclerotic Disease.

BACKGROUND AND PURPOSE: Understanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis is important for stroke triage and future trial design. The aim of this study was to characterize intrinsic MCA plaque and acute cerebral infarct in vivo by using high-resolution black-blood (BB) and diffusion-weighted magnetic resonance (MR) imaging and to investigate the relationship between plaque features and infarct patterns. METHODS: A single-center retrospective study was conducted at a tertiary referral center between March 2017 and August 2019. Patients consecutively admitted for acute ischemic stroke with MCA stenosis underwent diffusion-weighted and BB MR imaging. Plaque features and infarct patterns were assessed. The association between plaque features and infarct patterns (binary variable: single/multiple) was evaluated using a multivariate logistic regression model. RESULTS: Of 49 patients with MCA atherosclerotic stenosis, diffusion-weighted MR imaging showed that 28 patients (57%) had multiple acute cerebral infarcts and 21 patients had single acute cerebral infarcts. In contrast to single infarct, multiple infarcts were associated with greater plaque burden (81.9±7.24 versus 71.3±13.7; P=0.012). A multivariate logistic regression model adjusted for 7 potential confounders confirmed a statistically significant positive association between plaque burden and multiple acute infarcts (adjusted R2 =0.432, P< 0.001). The rate of plaque surface irregularity was significantly greater in patients with multiple infarcts than those with single infarct (71% versus 43%, P=0.044). For single acute penetrating artery infarct, patients with infarct size > 2cm had greater plaque burden compared with patients with infarct size < 2cm (75.3±13.4 versus 63.4±10.9; P = 0.016). CONCLUSIONS: Increased plaque burden, plaque surface irregularity in patients with MCA stenosis is associated with its likelihood to have caused an artery-to-artery embolism that produces multiple cerebral infarcts, especially along the border zone region, and increased plaque burden may promote subcortical single infarct size by occluding penetrating arteries. Our results provide important insight into stroke mechanism of MCA atherosclerosis.

Pre-Admission CHADS2 and CHA2DS2-VASc Scores on Early Neurological Worsening.

BACKGROUND: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. OBJECTIVE: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. METHODS: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. RESULTS: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. CONCLUSIONS: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.

Arterial elasticity, endothelial function and intracranial vascular health: A multimodal MRI study.

Vascular dysfunctions, including arterial stiffness and endothelial dysfunction, are prevalent in hypertensive subjects. We aimed to study their relations to subclinical intracranial vascular health in this study. A total of 200 older hypertensive males without overt cardiovascular or cerebrovascular diseases were recruited. Arterial elasticity was measured as carotid-femoral pulse wave velocity (cfPWV) and endothelial function was measured as digital reactive hyperemia index (RHI). Cerebrovascular health was evaluated using MRI in four aspects: intracranial atherosclerosis, brain perfusion as cerebral blood flow (CBF), vascular rarefaction analyzed as visible arterial branches on angiography using a custom-developed analysis technique and small vessel disease measured as white matter hyperintensity (WMH). There was a significant negative association between cfPWV and CBF, suggesting a link between arterial stiffness and CBF decline. Higher cfPWV was also associated with presence of intracranial stenotic plaque and greater WMH volume. RHI was positively related to CBF, indicating that endothelial dysfunction was associated with reduced CBF. All the associations remained significant after adjustment for confounding variables. Arterial stiffness and endothelial dysfunction are associated with reduced brain perfusion in older hypertensive males. Arterial stiffness is also associated with global cerebral vascular injury, affecting both small and medium-to-large arteries.

Current Advances in Endovascular Treatment of Intracranial Atherosclerotic Disease and Future Prospective.

OBJECTIVES/BACKGROUND: Medical therapy is the first line of treatment for intracranial atherosclerotic disease (ICAD). Percutaneous transluminal angioplasty and stenting (PTAS) are mainly considered for those patients with severe stenosis and recurrent events despite aggressive medical therapy. In this review, we discuss the application of PTAS as a treatment option for ICAD and its future prospect. MATERIALS AND METHODS: We did the literature review of the key articles and guidelines to elaborate on the role of PTAS in the management of ICAD based on the current data and expert opinion. We searched PubMed, Google Scholar, and Scopus up to August 2020, and included articles published only in the English language. RESULTS: Since the publication of the results from SAMMPRIS and VISSIT trials, stenting is no longer recommended for secondary stroke prevention in patients with symptomatic ICAD. However, recent clinical studies on intracranial stenting for a subgroup of ICAD patients have shown promising results, likely due to better patient selection and continued advancement of endovascular techniques. CONCLUSION: There exists a lack of consensus regarding the best endovascular treatment approach (e.g., angioplasty alone or balloon mounted stent vs. self-expanding stent with or without prior angioplasty) or management of in-stent restenosis. Another area of clinical controversy relates to the ideal use and duration of antiplatelet therapy.

Infarct Recurrence in Intracranial Atherosclerosis: Results from the MyRIAD Study.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism. METHODS: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks. RESULTS: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes. CONCLUSIONS: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121028.

Mechanism of Stroke According to the Severity and Location of Atherosclerotic Middle Cerebral Artery Disease.

BACKGROUND AND PURPOSE: Strategy for secondary prevention of ischemic stroke depends on the mechanism of stroke. The aim of this study was to compare the stroke mechanism according to the location and severity of middle cerebral artery (MCA) disease. METHODS: We analyzed acute ischemic stroke patients within 7 days of onset with symptomatic MCA disease. The location of MCA disease was classified into proximal MCA M1 (pMCA) and distal MCA M1/proximal M2 (dMCA). The mechanism of stroke was categorized according to the pattern of ischemic lesion: local branch occlusion, artery-to-artery embolism/hemodynamic infarction, in situ-thrombosis, or a combined mechanism. The mechanism and imaging characteristics of stroke were compared according to the location and severity. The factors associated with the stroke mechanism were also investigated. RESULTS: A symptomatic MCA disease was observed in 126 patients (74 pMCA and 52 dMCA). The mechanism of stroke differed according to the location (p < 0.001); the combined mechanism was most common in pMCA disease (54.1%), especially in those who presented with MCA occlusion and with a susceptible vessel sign. Artery-to-artery embolism/hemodynamic infarction was most common in dMCA disease (46.2%). A longer length of stenosis was observed in local branch occlusion than in other mechanisms (p = 0.04) and was an independent factor associated with local branch occlusion (OR=1.631, 95% CI=1.161-2.292; p = 0.005). CONCLUSIONS: The mechanism of stroke differed according to the location of MCA disease: occlusion caused by plaque rupture with combined mechanism of stroke type was predominant in pMCA. Longer length of stenosis was associated with local branch occlusion.

Treatment Approaches and Outcomes for Acute Anterior Circulation Stroke Patients with Tandem Lesions.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated intracranial LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p = 0.003), had less atrial fibrillation (13% vs 40%, p < 0.0001), less adequate reperfusion (TICI 2b-3, 58% vs 82%, p < 0.0001), more intracranial hemorrhage (ICH, 13% vs 5%, p = 0.037), but similar 90-day functional independence (mRS 0-2, 34% vs 43%, p = 0.181). The cervical ICA was treated before intracranial EVT (57%), after (13%), not acutely (22%), or was inaccessible (8%). Acute cervical ICA treatments were stenting (57%) or angioplasty alone (13%). Neither acute stenting nor order of treatment was associated with outcomes (TICI 2b-3, ICH, or 90-day mRS 0-2). Among acutely stented, neither alteplase nor antiplatelets were associated with outcomes or stent patency. CONCLUSIONS: Tandem lesions were associated with less reperfusion, more ICH, but similar 90-day functional independence. No treatment approach was associated with outcomes. These data illustrate the technical challenges of tandem lesion treatment and underscore the importance of developing new approaches.

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

Antegrade Blood Flow on 4-Dimensional Computed Tomography Angiography Predict Stroke Subtype in Patients With Acute Large Artery Occlusion.

Background The purpose of this study was to determine whether the presence of antegrade blood flow was related to stroke subtype in patients with acute intracranial large artery occlusion. Methods and Results The prospectively collected data for consecutive patients who had occlusion of the unilateral M1 segment of the middle cerebral artery with or without internal carotid artery and received reperfusion therapy were retrospectively reviewed. Stroke causes were determined according to the Trial of ORG 10172 in Acute Stroke Treatment standard. We defined antegrade flow as early opacification at the distal interface of the clot with subsequent distal extension on 4-dimensional computed tomography angiography. A total of 387 large artery occlusion patients were analyzed (229 men and 158 women; mean age, 71±14 years), including 77 (19.9%) with large artery atherosclerosis (LAA), 206 (53.2%) with cardioembolism, and 104 (26.9%) with undetermined causes. Antegrade flow was found in 206 (53.2%) patients, and 181 (46.8%) presented with retrograde flow. The rate of antegrade flow was much higher in patients with LAA than in those with cardioembolism (85.7% versus 42.2%, P<0.001). Multivariable logistic regression revealed that presence of antegrade flow was significantly associated with cuse of LAA after adjusting for confounding factors, when setting cardioembolism as reference (odds ratio, 5.650; 95% confidence interval, 2.451-13.158; P<0.001). The sensitivity, specificity, and positive and negative predictive values of the antegrade flow for predicting LAA were 43.1%, 91.5%, 85.7%, and 57.8%, respectively. Conclusions Using 4-dimensional computed tomography angiography, antegrade flow can be identified in more than half of acute anterior large artery occlusion patients and occurs more frequently in those with LAA as the cause of stroke.

Prognosis of Subtypes of Acute Large Artery Atherosclerotic Cerebral Infarction by Evaluation of Established Collateral Circulation.

BACKGROUND: The prognosis of acute ischemic stroke is related to collateral circulation, which is different with different pathogenesis. OBJECTIVE: To explore the prognosis of acute large atherosclerotic (LAA) cerebral infarction with different pathogenesis by assessing the establishment of collateral circulation. METHODS: 108 patients with acute LAA cerebral infarction in our hospital, who failed to thrombolytic or thrombectomy in the acute phase were selected and classified by Chinese ischemic stroke subclassification (CISS). They were evaluated by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). CT angiography (CTA) of head and neck were used to evaluate the collateral circulation for patients with large vessel stenosis or occlusion within one week of admission. The CTA collateral scores (CS) were recorded in a dichotomized fashion (ie, poor vs good). RESULTS: Patients with good CS had significantly lower NIHSS score and good prognosis at 2 weeks and 3 months than patients with poor CS (P < 0.001). The arterial-to-arterial embolization mechanism was the highest in the ratio of good CS and good prognosis at 3 months (P < 0.001). Multivariate Logistic regression analysis showed that baseline NIHSS score (OR=1.407, 95%CI:1.153-1.717, P=0.001) was an independent factor affecting poor CS. The NIHSS score at baseline (OR=0.604, 95%CI:0.436-0.837, P=0.002) and good CS (OR=39.552, 95%CI:8.908-175.618, P=0.000) were important predictors of good prognosis at 3 months. CONCLUSION: The prognosis and collateral circulation of acute LAA cerebral infarction with different pathogenesis was different. Baseline NIHSS score and collateral circulation had great impact on prognosis at 3 months.