Atherosclerotic Carotid Artery Stenosis Research Articles

Identification of microRNA biomarkers simultaneously expressed in circulating extracellular vesicles and atherosclerotic plaques.

Atherosclerosis is a widespread disorder of the cardiovascular system. The early detection of plaques by circulating biomarkers is highly clinically relevant to prevent the occurrence of major complications such as stroke or heart attacks. It is known that extracellular vesicles (EVs) are important in intercellular communication in atherosclerotic disorders and carry many components of their cells of origin, including microRNAs (miRNAs). In this study, we test the assumption that miRNAs present in material acquired from plaques in patients undergoing surgery for atherosclerotic carotid artery stenosis are also expressed in circulating EVs obtained from the identical patients. This would allow the adoption of a liquid biopsy approach for the detection of plaques. We studied 22 surgical patients with atherosclerotic carotid arterial stenosis and 28 healthy controls. EVs were isolated from serum by precipitation. miRNA expression profiles of serum-derived EVs were obtained by small RNA sequencing and in plaque material simultaneously acquired from patients. A comparative analysis was performed to identify circulating atherosclerosis-associated miRNAs that are also detectable in plaques. Seven miRNAs were found to be differentially regulated in patient serum compared with the serum of healthy controls. Of these, miR-193b-5p, miR-193a-5p, and miR-125a-3p were significantly upregulated in patients compared with that in healthy controls and present in both, circulating EVs and plaque material. An overrepresentation analysis of experimentally validated mRNA targets revealed an increased regulation of inflammation and vascular growth factors, key players in atherosclerosis and plaque formation. Our findings suggest that circulating EVs reflect plaque development in patients with symptomatic carotid artery stenosis, which can serve as biomarker candidates for detecting the presence of atherosclerotic plaques.

In-stent restenosis estimation following carotid artery stenting: The robust predictive value of atherogenic index of plasma and other non-traditional lipid profiles.

Atherosclerotic carotid artery stenosis is a significant contributor to ischemic strokes, and carotid artery stenting (CAS) has emerged as a pivotal treatment option. However, in-stent restenosis (ISR) remains a concern, impacting the long-term patency of CAS. This study aimed to investigate the predictive value of non-traditional lipid profiles, including the atherogenic index of plasma (AIP), in ISR development. This retrospective single-center study involved patients presenting at a tertiary healthcare facility with severe carotid artery disease between 2016 and 2020 who subsequently underwent CAS. A total of 719 patients were included in the study. The study cohort was divided into ISR and non-ISR groups based on restenosis presence, confirmed by angiography following ultrasonographic follow-up assessments. Non-traditional lipid indices, such as AIP, atherogenic index (AI), and lipoprotein combined index (LCI), were evaluated along with traditional risk factors. During a 24-month follow-up, ISR occurred in 4.03% of patients. To determine the predictors of restenosis, three different models were constructed in multivariate analysis for non-traditional lipid indices. Multivariate analysis revealed AIP as a robust independent predictor of ISR (OR: 4.83 (CI 95 % 3.05-6.63, p < .001). Notably, AIP demonstrated superior predictive accuracy compared to AI and LCI, with a higher Area Under the Curve (AUC) of 0.971. Non-traditional lipid profiles, especially AIP, were found to be associated with an increased risk of ISR and may serve as predictors of ISR in patients undergoing CAS.

Cilostazol-based dual antiplatelet treatment in ischemic stroke or transient ischemic attack patients with asymptomatic carotid artery disease: a propensity score matching analysis.

The optimal treatment for asymptomatic atherosclerotic carotid artery disease remains controversial. Data on the efficacy of antiplatelet agents and stroke outcomes are limited. This study aimed to examine the efficacy and safety of cilostazol-based dual antiplatelet therapy in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery disease. This retrospective cohort study was conducted in a tertiary-care setting and included baseline characteristics and clinical outcomes of participants. The study included patients who had experienced first-ever ischemic stroke or transient ischemic attack and asymptomatic atherosclerotic carotid artery stenosis, with a minimum follow-up period of 1 year. Asymptomatic carotid artery stenosis refers to stenosis in patients without neurological symptoms referable to the carotid arteries. Propensity scores were estimated using a logistic regression model based on participants' baseline characteristics. The efficacy outcome was the composite outcome of recurrent ischemic events and vascular-related death in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery stenosis. The safety outcome was the occurrence of hemorrhagic complications such as intracranial hemorrhages or extracranial hemorrhages. The effectiveness of dual therapy compared to monotherapy was evaluated at various time points following the initiation of antiplatelet treatment. This study included 516 patients with a 1-year follow-up period. At 1 year, composite events occurred in 10 (6.3%) patients in the dual antiplatelet group compared with 12 (7.6%) in the single antiplatelet group (HR, 0.74; 95% CI, 0.61-0.90; p = 0.024). Extracranial hemorrhage occurred in 12 (7.6%) patients in the dual antiplatelet group compared with nine (5.7%) in the single antiplatelet group (HR, 1.35; 95% CI, 1.13-1.48; p = 0.017). No intracranial hemorrhages were observed in this cohort. Patients with asymptomatic carotid artery stenosis who received cilostazol-based dual antiplatelet therapy had a lower risk of composite events but a higher risk of minor extracranial hemorrhage than those who received a single antiplatelet agent.

Evaluation of Turbulence Index and Flow Pattern for Atherosclerotic Carotid Stenosis: A High-Frame-Rate Vector Flow Imaging Study

ObjectiveThe emerging high-frame rate vector flow imaging (H-FRV Flow) provides a new way of hemodynamic evaluation for complex blood flow. This study aimed to explore quantitatively the characteristics of complex flow with turbulence (Tur) index and analyze flow pattern in atherosclerotic internal carotid artery stenosis (ICAS) using H-FRV Flow. MethodsThis study prospectively included 60 patients with ICAS. Tur values in different segments of stenosis and cardiac phases were compared. Meanwhile Spearman correlation analysis was performed between clinical plaque characteristics with turbulence grading by ln (Tur). Three complex flow patterns were qualitatively drawn on vector flow mode, and the detection rate of flow patterns in different stenosis groups and ulceration groups were compared. ResultsHighly disordered blood flow was observed in the stenosis (Tur (%) (M, QR) =12.5, 21.5) and distal segment (15.4, 27.2), particularly during systole (21.0, 30.7/ 33.3, 38.7, P<0.05). Spearman correlation analysis showed that stenosis rate was correlated with turbulence grading in the stenosis (ρ=0.65, P<0.05) and distal segment (ρ=0.79, P<0.05), and ulcer formation was correlated with turbulence grading in the stenosis segment (ρ=0.58, P<0.05). The overall detection rate of three flow patterns was higher respectively in the severe stenosis group (22/22) versus mild to moderate stenosis group (21/38) (P<0.001) and the ulcer group (21/23) versus non-ulcer group (23/37) (P<0.001). ConclusionH-FRV Flow was helpful for assess the severity and characteristics of flow turbulence. Lumen geometric factors could affect the flow turbulence and blood flow patterns around the plaque. This would provide important hemodynamic information for the detection of high-risk plaque.

Identification of pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis based on comprehensive bioinformatics analysis and machine learning.

Bioinformatics methods were applied to investigate the pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis (ACAS) and provide new insights for the treatment of this disease. The study utilized five ACAS datasets (GSE100927, GSE11782, GESE28829, GSE41571, and GSE43292) downloaded from the NCBI GEO database. The first four datasets were combined as the training set (n = 99), while GSE43292 (n = 64) was used as the validation set. Difference analysis and functional enrichment analysis were then performed on the training set. The pathogenic targets of ACAS were screened by protein-protein interaction networks and MCODE analyses, combined with three machine learning algorithms. The results were next verified by analysis of inter-group differences and ROC curve analysis. Next, immune-related function and immune cell correlation analyses were performed, and plaques of human ACAS were applied to verify the results via immunohistochemistry (IH) and immunofluorescence (IF). Finally, the competing endogenous RNAs (ceRNA) and transcription factors (TFs) regulatory networks of the characterized genes were constructed. A total of 177 differentially expressed genes were identified, including 67 genes downregulated and 110 genes upregulated. Gene set enrichment analysis revealed that five pathways were active in the experimental group, including xenograft rejection, autoimmune thyroid disease, graft-versus-host disease, leishmaniasis infection, and lysosomes. Four key genes were identified, with C3AR1 being upregulated and FBLN5, PPP1R12A, and TPM1 being downregulated. The analysis of inter-group differences demonstrated that the four characterized genes were differentially expressed in both the control and experimental groups. The ROC analysis showed that they had high AUC values in both the training and validation sets. Therefore, a predictive ACAS patient nomogram model based on the screened genes was established. Correlation analysis revealed a positive correlation between C3AR1 expression and neutrophils, which was further validated in IH and IF. One or multiple lncRNAs may compete with the characterized genes for binding miRNAs. Additionally, each characterized gene interacts with multiple TFs. Four pivotal genes were screened, and relevant ceRNA and TFs were predicted. These molecules may exert a crucial role in ACAS and serve as potential biomarkers and therapeutic targets.

Impaired cerebrovascular reactivity correlates with reduced retinal vessel density in patients with carotid artery stenosis: Cross-sectional, single center study.

The cerebral and retinal circulation systems are developmentally, anatomically, and physiologically interconnected. Thus, we hypothesized that hypoperfusion due to atherosclerotic stenosis of the internal carotid artery (ICA) can result in disturbances of both cerebral and retinal microcirculations. We aimed to characterize parameters indicating cerebrovascular reactivity (CVR) and retinal microvascular density in patients with ICA stenosis, and assess if there is correlation between them. In this cross-sectional study the middle cerebral artery (MCA) blood flow velocity was measured by transcranial Doppler (TCD) and, simultaneously, continuous non-invasive arterial blood pressure measurement was performed on the radial artery by applanation tonometry. CVR was assessed based on the response to the common carotid artery compression (CCC) test. The transient hyperemic response ratio (THRR) and cerebral arterial resistance transient hyperemic response ratio (CAR-THRR) were calculated. Optical coherence tomography angiography (OCTA) was used to determine vessel density (VD) on the papilla whole image for all (VDP-WIall) and for small vessels (VDP-WIsmall). The same was done in the peripapillary region: all (VDPPall), and small (VDPPsmall) vessels. The VD of superficial (VDMspf) and deep (VDMdeep) macula was also determined. Significance was accepted when p<0.05. Twenty-four ICA stenotic patients were evaluated. Both CVR and retinal VD were characterized. There was a significant, negative correlation between CAR-THRR (median = -0.40) and VDPPsmall vessels (median = 52%), as well as between VDPPall vessels (median = 58%), and similar correlation between CAR-THRR and VDP-WIsmall (median = 49.5%) and between VDP-WIall (median = 55%). The significant correlation between impaired cerebrovascular reactivity and retinal vessel density in patients with ICA stenosis suggests a common mechanism of action. We propose that the combined use of these diagnostic tools (TCD and OCTA) helps to better identify patients with increased ischemic or other cerebrovascular risks.

Risk factors for ischemic stroke in men and women aged 45–74 years

Stroke is one of the leading causes of death and primary disability and contributes significantly to the global burden of disease. Identification of individuals at high risk of ischemic stroke (IS) is an important component of disease prevention. The differences between risk factors (RF) for stroke in men and women are not well understood.Objective: to determine the predictive value of RF for the development of IS in men and women aged 45–74 years.Material and methods. The study included 728 patients (380 men and 348 women) aged 45–74 years, including 392 patients (247 men and 145 women) with IS in the carotid artery basin (main group) and 336 patients (133 men and 203 women) with vascular cognitive impairment (comparison group). To build predictive models to assess the impact of RF on the development of IS in men and women, we used the logistic regression method with stepwise exclusion of variables according to the Wald algorithm.Results. The predictive regression model of IS in men includes atherosclerotic stenosis of the internal carotid arteries [odds ratio (OR) 3.571; 95% confidence interval (CI) 1.792–7.114], in a predictive regression model in women – diabetes mellitus type 2 (OR 5.074; 95% CI 1.768–14.561) and a history of IS (OR 6.857; 95% CI 1.825–25.762). Other risk factors for the development of IS (atrial fibrillation, history of transient ischemic attack, arterial hypertension stage) affected both men and women.Conclusion. Atherosclerotic stenosis of the internal carotid arteries was found to be a sex-specific prognostic factor for IS in men, and type 2 diabetes mellitus and a history of IS in women.

Оценка влияния хирургической реконструкции внутренней сонной артерии на гемодинамику глаза и морфофункциональные показатели зрительного анализатора у пациентов с хронической ишемической нейрооптикопатией, ассоциированной с гемодинамически значимым атеросклеротическим стенозом внутренней сонной артерии

Purpose. To evaluate the effect of carotid endarterectomy (CEA) on eye hemodynamics and morphofunctional parameters of the visual analyzer in patients with chronic ischemic neuropathy (CIN) associated with hemodynamically significant atherosclerotic stenosis of the internal carotid artery (ICA). Material and methods. The study included 50 patients (50 eyes) with unilateral manifestations of CIN. All patients underwent optical coherence tomography (OCT), Doppler ultrasound of the ophthalmic artery (OA), short posterior ciliary arteries (SPCA), central retinal artery (CRA) before and after surgical reconstruction of the ICA. Results. 24 months after CEA of the ICA, in all cases there were significant improvements in blood flow in the OA by 52.8 %, in the SPCA by 26 %, in the CRA by 30.2 %, a decrease in the thickness of the peripapillary layer of retinal nerve fibers by 9.5 % and the layer of ganglionic cells by 8 % relative to baseline (p &lt; 0.05). Conclusion. The causes of CIN progression after ICA CEA can be considered as the consequences of induced reperfusion of the optic nerve structures and the brain. Keywords: chronic ischemic neuroopticopathy, ocular ischemic syndrome, internal carotid artery, carotid endarterectomy

Prediction of cerebral ischemia during carotid stenting depending on the intensity of the preoperative ultrasound signal from the plaque

Carotid stenting is an effective method for improving cerebral perfusion; risk assessment of cerebral embolism associated with this intervention remains a hot research topic. Objective: to identify predictors of cerebral embolism associated with carotid angioplasty with stenting (CAS). Material and methods. A prospective exploratory research included 46 patients (age from 44 to 81 years, median 65 years) with atherosclerotic stenosis of the internal carotid artery, who underwent CAS and were treated at the Scientific Center of Neurology (Moscow). The study did not include patients with restenosis, stroke with severe disability, contraindications for antiplatelet therapy, statins, and MRI examination. All patients underwent preoperative ultrasonographic (US) examination and postoperative histological examination of particles in carotid stent embolic protection devices. The state of the brain was assessed before and 24 hours after CAS using diffusion-weighted MRI. To identify predictors of the development of cerebral embolism, the clinical characteristics of patients, together with ultrasonographic and morphological data, were examined in a multivariate statistical analysis.Results. Preoperative US signal from an atherosclerotic plaque of high (estimated above 35 dB) intensity was associated with dense matter (in a protective device) of the "fibrosis with calcification" and "calcification" type and with a high probability (80%; 95% confidence interval 71–85% ) predicted intraoperative embolization of cerebral vessels with the acute ischemic lesions (AIL) formation. In a low (not higher than 35 dB) intensity of the preoperative ultrasound signal, the probability of AIL formation was statistically significantly lower (50%). Conclusion. There is a direct correlation between the intensity of the ultrasound signal and the density of the substance in the protective device. A high intensity of the preoperative ultrasound signal (estimated above 35 dB) is an unfavorable predictor of AIL, associated with CAS (with a probability of about 80%).

Potential Biomarkers and Therapeutic Targets: Inflammation and Oxidative Stress in Left Carotid Artery Stenosis with Coronary Artery Disease.

Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether markers of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2-isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.

Abstract Number ‐ 216: Limb‐Shaking Transient Ischemic Attack in the Setting of Moyamoya Disease

Introduction Moyamoya disease (MMD) is a cerebrovascular disorder characterized by progressive narrowing of the large intracranial arteries, primarily the internal carotid artery (ICA) and its branches, with secondary development of prominent small‐vessel collaterals. Limb shaking is a rare manifestation of transient ischemic attack (TIA) that is characterized by brief, irregular, involuntary jerking of the arms or legs and momentary disorientation without complete loss of consciousness. It is mainly associated with high grade carotid stenosis. In rare cases, limb‐shaking TIA can occur in the setting of MMD. Methods The patient was identified in routine clinical practice. Results A woman in her 50s presented with a six‐year history of progressive weakness below the neck when standing and initiating movement. These episodes were followed by violent shaking of her arms and legs that lasted several seconds to minutes. She reported transient confusion after the events, but no seizure activity was seen on multiple EEGs, and anti‐epileptic drugs (AEDs) failed to alleviate her symptoms. Further neurological workup included a MR angiogram of the brain that was suggestive of MMD. Catheter angiography confirmed bilateral occlusion of the M1 segments of the middle cerebral arteries (MCAs) and the A1 segment of the left anterior cerebral artery (ACA). There was neovascularization in the same territories with significant collateral flow from the posterior circulation. She was diagnosed with bilateral limb‐shaking TIA in the setting of MMD. She recently underwent two revascularization procedures, a left superficial temporal artery (STA) to middle cerebral artery (MCA) bypass and a right sided encephaloduroarteriosynangiosis (EDAS). Conclusions Limb‐shaking TIA is predominantly associated with severe atherosclerotic extracranial carotid artery stenosis. In rare cases, the limb‐shaking episodes are caused by cerebral hypoperfusion secondary to severe stenosis of the ICAs, and their branches, in the setting of moyamoya disease. Treatment of limb‐shaking TIA to prevent further brain ischemia includes adjustment of fluid intake, careful blood pressure management to avoid episodes of relative brain hypoperfusion, and revascularization procedures. Revascularization is also the most effective method of treating MMD and patients will often experience improvement of their symptoms within one year. Early recognition of limb‐shaking TIA in MMD is critical to avoid unnecessary and potentially harmful treatments (e.g. AEDs), provide patients with accurate explanations of their symptoms, and ensure timely administration of the appropriate treatments.

A Delphi Consensus Study on Undergoing Carotid Endarterectomy: Patient Reported Outcome Measures

Currently, evidence is lacking for disease specific patient reported outcome measures (PROMs) for use in atherosclerotic carotid artery stenosis (either symptomatic or asymptomatic) submitted to carotid endarterectomy (CEA). This study aimed to obtain expert consensus on the most important items to include in a PROM designed to capture the impact of atherosclerotic carotid artery stenosis and its treatment on health related quality of life. A three round modified Delphi consensus study was performed. A mixed expert Delphi panel of doctors (international panel of dedicated vascular surgeons and neurologists) and patients (either symptomatic or asymptomatic patients meeting criteria for carotid artery revascularisation) was implemented. The aim was to obtain pre-defined consensus on items in four pre-defined domains: generic, quality of life, symptom related, and treatment related. Consensus was reached in rounds 2 and 3 with > 70% overall expert agreement. The experts agreed on 23 items (out of 49) which were distributed as follows: five in the generic, six in the quality of life, six in the symptom, and six in the treatment related domain. Interestingly, comparing the items that reached consensus in this study, with the generic and disease specific PROMs previously used in carotid artery disease investigation, the only constant items were "difficulty with walking" and "ability to perform daily activities" included in the symptom domain. Considering the items that reached expert consensus in the additional domains, emphasis was given to the impact of the diagnosis, treatment and follow up, and to fear/concern "about the future" and "about severe stroke". In the treatment domain emphasis was also attained on the side effects, long term patient satisfaction, and on the information provided regarding treatment options. As hard clinical outcomes become increasingly rare, assessment of the impact of CEA becomes increasingly difficult. The consensus reached provides a newly defined disease specific PROM that warrants independent validation in specific populations in the future.

Optical coherence tomography angiography in diagnosis of changes in macular capillary blood flow in chronic ischemic retinopathy

Assessment of the indices of macular capillary blood flow and subfoveal choroidal thickness (SCT) using optical coherence tomography angiography in patients with retinal manifestations of ocular ischemic syndrome (RMOIS) associated with atherosclerotic internal carotid artery stenosis. The study included 34 patients (68 eyes): 21 men, 13 women with RMOIS in one eye. All patients were divided into 2 groups depending on the severity of atherosclerotic internal carotid artery stenosis and ophthalmoscopic picture of the fundus. To obtain objective information we analyzed the degree of decrease in the main indices characterizing macular microcirculation and SCT depending on the severity of RMOIS. Analysis of the results showed relationship between the severity of RMOIS and the deficit in macular microcirculation. The macula of the patients with mild RMOIS was characterized by a decrease in the density of superficial vascular plexus (SVP) and the density of deep capillary plexus (DCP) by 13.5% and 10.5% compared to the controls, respectively; in moderate RMOIS - by 19.7% and 14.6%; in severe RMOIS - by 35.9% and 28%, respectively. With an increase in the severity of RMOIS, the area of the foveal avascular zone increased too: in mild degree RMOIS - by 19%, in moderate - by 38.6%, in severe - by 51%. In proportion to the severity of RMOIS, SCT was reduced: in mild degree RMOIS - by only 8%, in moderate - by 22%, and in severe - by 29.8% of the control. The conducted research indicates that pathological changes in RMOIS extend to the entire capillary network of the macula and SCT. With increase in the degree of RMOIS, ischemic changes in all capillary layers of the central parts of the retina proportionally increase in comparison with the control group by 1.15 times in mild degree, by 1.24 times in moderate degree, and by 1.5 times in severe RMOIS.

MicroRNAs Associated with Carotid Plaque Development and Vulnerability: The Clinician’s Perspective

Ischemic stroke (IS) related to atherosclerosis of large arteries is one of the leading causes of mortality and disability in developed countries. Atherosclerotic internal carotid artery stenosis (ICAS) contributes to 20% of all cerebral ischemia cases. Nowadays, atherosclerosis prevention and treatment measures aim at controlling the atherosclerosis risk factors, or at the interventional (surgical or endovascular) management of mature occlusive lesions. There is a definite lack of the established circulating biomarkers which, once modulated, could prevent development of atherosclerosis, and consequently prevent the carotid-artery-related IS. Recent studies emphasize that microRNA (miRNA) are the emerging particles that could potentially play a pivotal role in this approach. There are some research studies on the association between the expression of small non-coding microRNAs with a carotid plaque development and vulnerability. However, the data remain inconsistent. In addition, all major studies on carotid atherosclerotic plaque were conducted on cell culture or animal models; very few were conducted on humans, whereas the accumulating evidence demonstrates that it cannot be automatically extrapolated to processes in humans. Therefore, this paper aims to review the current knowledge on how miRNA participate in the process of carotid plaque formation and rupture, as well as stroke occurrence. We discuss potential target miRNA that could be used as a prognostic or therapeutic tool.

Early Diagnosis of Intracranial Internal Carotid Artery Stenosis Using Extracranial Hemodynamic Indices from Carotid Doppler Ultrasound.

Atherosclerotic intracranial internal carotid artery stenosis (IICAS) is a leading cause of strokes. Due to the limitations of major cerebral imaging techniques, the early diagnosis of IICAS remains challenging. Clinical studies have revealed that arterial stenosis may have complicated effects on the blood flow’s velocity from a distance. Therefore, based on a patient-specific one-dimensional hemodynamic model, we quantitatively investigated the effects of IICAS on extracranial internal carotid artery (ICA) flow velocity waveforms to identify sensitive hemodynamic indices for IICAS diagnoses. Classical hemodynamic indices, including the peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI), were calculated on the basis of simulations with and without IICAS. In addition, the first harmonic ratio (FHR), which is defined as the ratio between the first harmonic amplitude and the sum of the amplitudes of the 1st–20th order harmonics, was proposed to evaluate flow waveform patterns. To investigate the diagnostic performance of the indices, we included 52 patients with mild-to-moderate IICAS (<70%) in a case–control study and considered 24 patients without stenosis as controls. The simulation analyses revealed that the existence of IICAS dramatically increased the FHR and decreased the PSV and EDV in the same patient. Statistical analyses showed that the average PSV, EDV, and RI were lower in the stenosis group than in the control group; however, there were no significant differences (p > 0.05) between the two groups, except for the PSV of the right ICA (p = 0.011). The FHR was significantly higher in the stenosis group than in the control group (p < 0.001), with superior diagnostic performance. Taken together, the FHR is a promising index for the early diagnosis of IICAS using carotid Doppler ultrasound methods.

Association of distal hyperintense vessel sign and recurrent stroke in patients with symptomatic intracranial stenosis

ObjectiveThe distal hyperintense vessel sign (DHV) on fluid-attenuated inversion recovery magnetic resonance image (MRI) is an imaging biomarker of slow leptomeningeal collateral flow in the presence of large artery stenosis or occlusion reflecting impaired cerebral hemodynamics. In this study, we aim to investigate the significance of the DHV sign in patients with symptomatic ≥ 70% intracranial atherosclerotic stenosis. MethodsWe retrospectively reviewed patients with ischemic stroke or transient ischemic attack admitted to a single center from January 2010 to December 2017. Patients were included if they had symptomatic ≥ 70% atherosclerotic stenosis of the intracranial internal carotid artery or middle cerebral artery. The presence of the DHV sign was evaluated by blinded neuroradiologist and vascular neurologists. Recurrent ischemic stroke in the vascular territory of symptomatic intracranial artery was defined as new neurological deficits with associated neuroimaging findings during the follow up period. ResultsA total of 109 patients were included in the study, of which 55 had DHV sign. Average duration of follow up was 297 ± 326 days. Four patients were lost during follow up. Patients with the DHV sign had a higher rate of recurrent ischemic stroke (38%), compared to patients without the DHV sign (17%; p=0.018). In multivariate regression analysis, the presence of DHV sign was an independent predictor of recurrent ischemic stroke. A DHV score of ≥ 2 had a 63% sensitivity and 69% specificity for recurrent ischemic stroke. InterpretationIn patients with severe symptomatic intracranial atherosclerotic stenosis, those with a DHV sign on MRI are at higher risk of recurrent ischemic stroke.

Angioplasty and Stenting for Carotid Artery Near-Occlusion

Carotid near-occlusion (CNO) is the type of severe atherosclerotic stenosis of the internal carotid artery (ICA) with or without collapse of the vessel distally to the narrow part. According to the North American Symptomatic Carotid Endarterectomy Trial (NASCET), severity of ICA stenosis highly correlates with the risk of stroke, except for cases of extremely critical stenosis &gt; 94%, where the risk is lower, and, according to recent guidelines, conservative treatment is preferable. This consideration is questionable due to the recent data about early stroke recurrence and worldwide practice. Rapid improvement of endovascular technique during the last decade makes carotid angioplasty and stenting (CAS) a feasible option for the treatment of patients with CNO and is widely reported in the literature. However, in uncertain circumstances, more scientific data are necessary to fulfill the gap in indications, terms and risks of CAS for CNO.&#x0D; The aim. To evaluate the results of the treatment of patients with CNO after CAS.&#x0D; Materials and methods. Three hundred and fifteen patients were surgically treated at Scientific-Practical Center of Endovascular Neuroradiology of the National Academy of Medical Sciences of Ukraine due to ICA stenosis between 2010 and 2020. Among them, 39 (12.4%) patients (11 woman / 28 men (age 57.9±2.1 years) had CNO and underwent CAS at our Center. Patient population, clinical and radiological investigations, procedure compli-cations were investigated. Procedure complications (stroke, hemodynamic depression [HD] and hyperperfusion syndrome [HPS]) were meticulously studied. All the patients had routine ultrasound and clinical check 30 days after the procedure.&#x0D; Results. All the patients with CNO were successfully stented with the improvement of the site of stenosis after CAS, with only minimal residual stenosis in cases of severe HD. We observed two procedural vascular accidents, first patient had transient ischemic attack (TIA) and one had stroke due to middle cerebral artery occlusion after stent placement and further urgent mechanical thrombectomy. The patient had no neurologic decline and was discharged home. We didn’t observe any cases of myocardial infarction (MI) or death in our series during the hospital stay. HD was seen in 13 (33.3%) patients, and mostly resolved after the procedure except for 3 casesthat required prolonged intensive care unit stay. HPS was diagnosed in 2 (5.1%) patients and also didn’t have anyneurologic consequences after supportive care. During 30 days of follow-up, one (2.6%) patient had TIA because of anti-platelets cessation and 1 (2.6%) patient had MI after 1 week since discharge. All control images revealedstents patency without the evidence of critical residual stenosis.&#x0D; Conclusions. CNO remains important diagnostic and therapeutic challenge. Recent data showed high risk ofrecurrent stroke in case of CNO on best medical therapy, especially at an early stage, but it remains a preferred option according to guidelines. Considering worldwide improvement of stroke rates after CAS in patients with symptomatic ICA stenosis, further studies are warranted to evaluate its risk-benefit in case of CNO, especially with full collapse. Our data shows that CAS with careful preoperative diagnosis and planning is an effective procedure for selected patients with CNO.

Real-time angiography in endovascular revascularization of intracranial atherosclerotic internal carotid artery stenosis under proximal balloon protection: “Retrograde suction-injection” technique and literature review

Intracranial angioplasty/stenting is a treatment option for patients with symptomatic intracranial atherosclerotic disease refractory to aggressive medical treatment. However, it carries a risk of procedure-related embolism as well as reperfusion hemorrhage and in-stent thrombosis. We have devised a new embolic protection system which can achieve both total ipsilateral internal carotid artery (ICA) embolic protection and real-time visualization of the target lesion during endovascular revascularization of intracranial atherosclerotic disease below the carotid T junction. Herein, we describe a case of medically refractory symptomatic intracranial atherosclerotic ICA stenosis successfully treated with this method.

Contrast agent retention sign in angiography predicts acute internal carotid artery embolic occlusion

BackgroundIdentification of acute internal carotid artery embolism (ICAE) and internal carotid artery atherosclerotic stenosis (ICAAS) in acute ischemic stroke patients is important for selection of treatment. The presence of contrast agent retention on pre-procedural angiographic images is more common in patients with ICA occlusion caused by embolism compared to patients with ICA atherosclerotic stenosis. This study aimed to evaluate effectiveness of contrast agent retention sign for predicting ICAE. MethodsSixty-five patients with ICA occlusion who underwent emergency endovascular treatment from September 2014 to September 2020 were included in this retrospective analysis. Patients were divided into ICAE (n = 46) and ICAAS (n = 19) groups. Clinical characteristics, imaging data and ICA contrast agent retention signs of patients were collected. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnosis accuracy of contrast agent retention sign were conducted. ResultsThe positive ICA contrast agent retention sign was significantly more common in patients with ICAE (60.87% vs 0.00%, P < 0.001) than that of patients with ICAAS, but significantly lower in male patients (53.57% vs 81.08%, P = 0.017). There were significantly more patients with positive sign had occlusion in C6 segment (64.29% vs 13.51%, P < 0.001) and no outflow tract (85.71% vs 5.41%, P < 0.001) compared with negative sign group. There were significantly fewer patients with postive sign had occlusion in C1 segment (0.00% vs 40.54%, P < 0.001) compared with negative sign group. The sensitivity, specificity, PPV, NPV and diagnosis accuracy of contrast agent retention sign for predicting ICAE occlusion were 60.87%, 100%, 100%, 51.35% and 72.31%, respectively. ConclusionThe ICA contrast agent retention sign has very high specificity and moderate sensitivity for detection of acute ICAE.

Влияние каротидной эндартерэктомии на функциональную активность зрительного анализатора у пациентов с хронической ишемической нейрооптикопатией, ассоциированной с гемодинамически значимым атеросклеротическим стенозом внутренней сонной артерии

Purpose. To assess the effect of carotid endarterectomy on the functional activity of the visual analyzer, based on the registration of visually evoked potentials in patients with chronic ischemic neuroopticopathy (CIN) associated with hemodynamically significant atherosclerotic stenosis of the internal carotid artery (ICA). Material and methods. The main group included patients with CIN (20 people, 20 eyes). Their age varied from 61 to 78 years (average 70 ± 4.5 years). Men – 13 people, women – 7. Of the specialized methods, the study of visual evoked potentials (VEP) was performed. Results. By the end of the follow-up (12 months), there was a decrease in the maximum corrected visual acuity below the preoperative values and an increase in the negative dynamics of the VEP values. There was an increase in the latency of the main peak by 13.2 % compared with the control and a decrease in amplitude by 34 % during stimulation with the pattern for both 30 and 60 minutes. Conclusion. Our studies have shown that further studies are required to develop an integrated approach to the treatment of CIN associated with hemodynamically significant atherosclerotic stenosis of the ICA. Keywords: visual evoked potentials, chronic ischemic neuroopticopathy, ocular ischemic syndrome, hemodynamically significant stenosis of the internal carotid artery.