Aphasia due to right hemisphere infarction in a patient with situs inversus after carotid artery stenting: a case report.

BACKGROUND: Situs inversus (SI) is a rare congenital anomaly in which systemic organs and vessels are positioned in a mirror image of their normal positions. An interesting issue regarding individuals with such a condition is whether they also have reversed brain asymmetries. Most of studies on this issue indicate that, similarly to many people with normal visceral alignment, patients with SI have a left hemispheric dominance for language functions. CASE PRESENTATION: We report a rare occurrence of anomalous cerebral dominance for language in a patient with complete situs inversus. The right-handed patient developed aphasia after carotid stenting, and brain magnetic resonance imaging showed cerebral infarction in the right parietal lobe. CONCLUSION: Anomalous cerebral dominance for language and visceral situs inversus in our patient both may result from a single, genetically coded atypicality of developmental gradient.

[Treatment of tandem occlusions of the common and internal carotid arteries]. / Behandlung von Tandemstenosen der A. carotis communis und A. carotis interna.

BACKGROUND: Proximal carotid tandem lesions are defined as multilevel lesions with significant (> 50%) atherosclerotic disease involving the internal carotid artery (ICA) in combination with the proximal ipsilateral common carotid artery (CCA) or innominate artery (IA). It is a relatively rare disease with an incidence of less than 5% in all patients with carotid stenosis at the level of the bifurcation. METHODS: These patients are at high surgical risk and were, therefore, excluded from current randomized controlled trials. Although the effectiveness of carotid endarterectomy (CEA) and carotid stenting (CAS) in stroke prevention for patients is established, the optimal treatment approach for the subgroup of patients with a proximal tandem lesion is still controversial. Treatment of this condition is not well understood because it is difficult to determine the risk of each individual lesion becoming symptomatic. Therefore, concurrent treatment of severe (> 70% stenosis) proximal lesions is recommended when treating severe stenosis at the carotid bifurcation. CONCLUSION: This disease can lead to embolic ischemic strokes or hemodynamic compromise. It is not possible to determine diagnostically which lesion led to the clinical symptoms, which is why both lesions should be corrected.

SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.

Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.

Cerebral hypoperfusion exacerbates vascular dysfunction after traumatic brain injury.

Traumatic brain injuries are extremely common, and although most patients recover from their injuries many TBI patients suffer prolonged symptoms and remain at a higher risk for developing cardiovascular disease and neurodegeneration. Moreover, it remains challenging to identify predictors of poor long-term outcomes. Here, we tested the hypothesis that preexisting cerebrovascular impairment exacerbates metabolic and vascular dysfunction and leads to worse outcomes after TBI. Male mice underwent a mild surgical reduction in cerebral blood flow using a model of bilateral carotid artery stenosis (BCAS) wherein steel microcoils were implanted around the carotid arteries. Then, 30 days post coil implantation, mice underwent TBI or sham surgery. Gene expression profiles, cerebral blood flow, metabolic function, oxidative damage, vascular health and angiogenesis were assessed. Single nuclei RNA sequencing of endothelial cells isolated from mice after TBI showed differential gene expression profiles after TBI and BCAS, that were further altered when mice underwent both challenges. TBI but not BCAS increased mitochondrial oxidative metabolism. Both BCAS and TBI decreased cerebrovascular responses to repeated whisker stimulation. BCAS induced oxidative damage and inflammation in the vasculature as well as loss of vascular density, and reduced the numbers of angiogenic tip cells. Finally, intravascular protein accumulation was increased among mice that experienced both BCAS and TBI. Overall, our findings reveal that a prior vascular impairment significantly alters the profile of vascular health and function of the cerebrovasculature, and when combined with TBI may result in worsened outcomes.

Outcomes in acute carotid-related stroke eligible for mechanical reperfusion: SAFEGUARD-STROKE Registry.

BACKGROUND: Carotid-related strokes (CRS) are largely unresponsive to intravenous thrombolysis and are often large and disabling. Little is known about contemporary CRS referral pathways and proportion of eligible patients who receive emergency mechanical reperfusion (EMR). METHODS: Referral pathways, serial imaging, treatment data, and neurologic outcomes were evaluated in consecutive CRS patients presenting over 18 months in catchment area of a major carotid disease referral center with proximal-protected CAS expertise, on-site neurology, and stroke thrombectomy capability (Acute Stroke of CArotid Artery Bifurcation Origin Treated With Use oF the MicronEt-covered CGUARD Stent - SAFEGUARD-STROKE Registry; companion to SAFEGUARD-STROKE Study NCT05195658). RESULTS: Of 101 EMR-eligible patients (31% i.v.-thrombolyzed, 39.5% women, age 39-89 years, 94.1% ASPECTS 9-10, 90.1% pre-stroke mRS 0-1), 57 (56.4%) were EMR-referred. Referrals were either endovascular (Comprehensive Stroke Centre, CSC, 21.0%; Stroke Thrombectomy-Capable CAS Centre, STCC, 70.2%) or to vascular surgery (VS, 1.8%), with >1 referral attempt in 7.0% patients (CSC/VS or VS/CSC or CSC/VS/STCC). Baseline clinical and imaging characteristics were not different between EMR-treated and EMR-untreated patients. EMR was delivered to 42.6% eligible patients (emergency carotid surgery 0%; STCC rejections 0%). On multivariable analysis, non-tandem CRS was a predictor of not getting referred for EMR (OR 0.36; 95%CI 0.14-0.93, P=0.03). Ninety-day neurologic status was profoundly better in EMR-treated patients; mRS 0-2 (83.7% vs. 34.5%); mRS 3-5 (11.6% vs. 53.4%), mRS 6 (4.6% vs. 12.1%); P<0.001 for all. CONCLUSIONS: EMR-treatment substantially improves CRS neurologic outcomes but only a minority of EMR-eligible patients receive EMR. To increase the likelihood of brain-saving treatment, EMR-eligible stroke referral and management pathways, including those for CSC/VS-rejected patients, should involve stroke thrombectomy-capable centres with endovascular carotid treatment expertise.

Next-generation transcarotid artery revascularization: TransCarotid flOw Reversal Cerebral Protection And CGUARD MicroNET-Covered Embolic Prevention Stent System To Reduce Strokes - TOPGUARD Study.

BACKGROUND: Stent-assisted carotid artery revascularization employing surgical cutdown for transcervical access and dynamic flow reversal (TCAR) is gaining popularity. TCAR, despite maximized intra-procedural cerebral protection, shows a marked excess of 30-day neurologic complications in symptomatic vs. asymptomatic stenoses. The TCAR conventional single-layer stent (free-cell area 5.89mm2) inability to seal embologenic lesions may be particularly relevant after the flow reversal neuroprotection is terminated. METHODS: We evaluated peri-procedural and 30-day major adverse cerebral and cardiac events (MACCE) of TCAR (ENROUTE, SilkRoad Medical) paired with MicroNET-covered neuroprotective stent (CGuard, InspireMD) in consecutive patients at elevated risk of complications with transfemoral/transradial filter-protected stenting (increased lesion-related and/or access-related risk). CGuard (MicroNET free cell area ≈0.02-0.03 mm2) has level-1 evidence for reducing intra- and abolishing post-procedural lesion-related cerebral embolism. RESULTS: One hundred and six increased-risk patients (age 72 [61-76] years, median [Q1-Q3]; 60.4% symptomatic, 49.1% diabetic, 36.8% women, 61.3% left-sided index lesion) were enrolled in three vascular surgery centers. Angiographic stenosis severity was 81 (75-91)%, lesion length 21 (15-26)mm, increased-risk lesional characteristics 87.7%. Study stent use was 100% (no other stent types). 74.5% lesions were predilated; post-dilatation rate was 90.6%. Flow reversal duration was 8 (5-11)min. One stroke (0.9%) occurred in an asymptomatic patient prior to establishing neuroprotection (index lesion disruption with the sheath insertion wire); there were no other peri-procedural MACCE. No further adverse events occurred by 30-days. 30-day stent patency was 100% with normal velocities and absence of any in-stent material by Duplex Doppler. CONCLUSIONS: Despite a high proportion of increased-risk lesions and clinically symptomatic patients in this study, TCAR employing the MicroNET-covered anti-embolic stent showed 30-day MACCE rate <1%. This suggests a clinical role for combining maximized intra-procedural prevention of cerebral embolism by dynamic flow reversal with anti-embolic stent prevention of peri- and post-procedural cerebral embolism (TOPGUARD NCT04547387).

Carotid artery stenting with flow inversion cerebral protection and MicroNet-covered stent.

BACKGROUND: The study aims to evaluate the association of proximal flow-inversion cerebral protection and MicroNet-covered CGuard stents in reducing early and late embolic events in carotid artery stenting procedures. METHODS: From 2018 to 2023, we performed 204 procedures in 180 patients with flow inversion cerebral protection and CGuard stents at the Vascular Surgery Unit of Sant'Eugenio Hospital in Rome. Cerebral protection was achieved with a Flow-Gate2 catheter connected to a peripheral vein. The tip balloon is inflated in the CCA to obtain an effective endoclamping, the pressure difference between the carotid bifurcation and the venous compartment ensures a constant back flow with wash-out in the venous compartment. Inclusion criteria were: life expectancy of >12 months, target lesions indicating treatment according to ESVS Guidelines, increased surgical risk due to comorbidities or anatomic issues. ECD follow-up was performed immediately postoperatively, at 30 days, 6 and 12 months, and subsequently annually. RESULTS: The treatment protocol was successfully implemented in 99% of cases. No major strokes occurred, while one minor stroke (0.5%) occurred within 8 hours of the procedure, regressing in the following months. One perioperative death (0.5%) due to cerebral hemorrhage occurred three hours after the procedure. All patients remained asymptomatic, with no short or medium-term neurological score deterioration. One hemodynamically significant restenosis (0.5%) was detected at the 6-month follow-up. All patients completed the 6 months follow-up, though 6 (3%) were lost at the 12-month appointment. CONCLUSIONS: Our prospective monocentric study has demonstrated the effectiveness and safety of the FlowGate2 flow inversion cerebral protection system in association with MicroNet covered CGuard stent.

Navigating complexity with low-crossing profile dual-layer micromesh carotid stent: implications for contemporary carotid artery stenting outcomes (ROADSAVER study insights).

BACKGROUND: The safety and efficacy of carotid artery stenting (CAS) can be affected by certain technical and anatomical factors. However, it is not known whether the use of a dual-layer micromesh stent (DLMS) with a low-crossing profile could reduce the risks associated with complex vascular anatomies during CAS. METHODS: This study involved 1965 asymptomatic or symptomatic carotid artery stenosis patients who received the Roadsaver DLMS during CAS, as part of a prospective, multicenter observational ROADSAVER study, conducted from January 2018 to February 2021. The primary outcome was the 30-day rate of major adverse events (MAE; i.e. any death or stroke) after CAS. Procedural details and outcomes were compared between patients with complex anatomical features and those without. RESULTS: One or more complex anatomical characteristics were identified in 1639 (83.4%) patents. Patients with complex anatomies were older and had a higher prevalence of arterial hypertension, cardiovascular disease, and prior stroke. Between patients with or without complex anatomical features, no significant differences were found either in procedural techniques, or in 30-day MAE (age-adjusted odds ratio (95% CI) for complexities vs. no complexities: 0.76 (0.35, 1.66); p=0.4905) and any stroke (age-adjusted odds ratio (95% CI) for complexities vs. no complexities: 0.89 (0.37, 2.17); p=0.8032) incidence. Furthermore, neither the presence of specific types of anatomic complexity nor their number (per patient) markedly influenced the 30-day MAE and any stroke incidence. CONCLUSIONS: In this real-world cohort of patients undergoing CAS with the Roadsaver DLMS, no significant difference in the occurrence of 30-day MAE and any stroke was observed between patients with or without high-risk anatomical features.

A meta-analysis supporting the superiority of staged carotid artery stenting and coronary artery bypass grafting in patients with concurrent severe coronary and carotid artery stenosis.

BACKGROUND: This study sought to ascertain whether a staged approach involving carotid artery stenting (CAS) and coronary artery bypass grafting (CABG) holds superiority over the synchronous (Syn) strategy of CAS or carotid endarterectomy (CEA) and CABG in patients necessitating combined revascularization for concurrent carotid and coronary artery disease. METHOD: Studies were identified through 3 databases: PubMed, EMBASE, and the Cochrane Library. Statistical significance was defined as a P value of less than .05 for all analyses, conducted using STATA version 12.0. RESULTS: In the comparison between staged versus Syn CAS and CABG for patients with concomitant severe coronary and carotid stenosis, 4 studies were analyzed. The staged procedure was associated with a lower rate of 30-day stroke (OR = 8.329, 95% CI = 1.017-69.229, P = .048) compared to Syn CAS and CABG. In the comparison between staged CAS and CABG versus Syn CEA and CABG for patients with concomitant severe coronary and carotid stenosis, 5 studies were examined. The staged CAS and CABG procedure was associated with a lower rate of mortality (OR = 2.046, 95% CI = 1.304-3.210, P = .002) compared to Syn CEA and CABG. CONCLUSION: The Syn CAS and CABG was linked to a higher risk of peri-operative stroke compared to staged CAS and CABG. Additionally, patients undergoing staged CAS and CABG exhibited a significantly decreased risk of 30-day mortality compared to Syn CEA and CABG. Future randomized trials or prospective cohorts are essential to confirm and validate these findings.

Inflammatory Biomarkers to Predict Major Adverse Cardiovascular Events in Patients with Carotid Artery Stenosis.

Background and Objectives: Inflammatory proteins and their prognostic value in patients with carotid artery stenosis (CAS) have not been adequately studied. Herein, we identified CAS-specific biomarkers from a large pool of inflammatory proteins and assessed the ability of these biomarkers to predict adverse events in individuals with CAS. Materials and Methods: Samples of blood were prospectively obtained from 336 individuals (290 with CAS and 46 without CAS). Plasma concentrations of 29 inflammatory proteins were determined at recruitment, and the patients were followed for 24 months. The outcome of interest was a major adverse cardiovascular event (MACE; composite of stroke, myocardial infarction, or death). The differences in plasma protein concentrations between patients with vs. without a 2-year MACE were determined using the independent t-test or Mann-Whitney U test to identify CAS-specific prognostic biomarkers. Kaplan-Meier and Cox proportional hazards analyses with adjustment for baseline demographic and clinical characteristics were performed to assess the prognostic value of differentially expressed inflammatory proteins in predicting a 2-year MACE in patients with CAS. Results: The mean age of the cohort was 68.8 (SD 10.2) years and 39% were female. The plasma concentrations of two inflammatory proteins were significantly higher in individuals with a 2-year MACE relative to those without a 2-year MACE: IL-6 (5.07 (SD 4.66) vs. 3.36 (SD 4.04) pg/mL, p = 0.03) and CD163 (233.825 (SD 230.306) vs. 159.673 (SD 175.669) pg/mL, p = 0.033). Over a follow-up period of 2 years, individuals with elevated levels of IL-6 were more likely to develop MACE (HR 1.269 (95% CI 1.122-1.639), p = 0.042). Similarly, over a 2-year period, patients with high levels of CD163 were more likely to develop MACE (HR 1.413 (95% CI 1.022-1.954), p = 0.036). Conclusions: The plasma levels of inflammatory proteins IL-6 and CD163 are independently associated with adverse outcomes in individuals with CAS. These CAS-specific prognostic biomarkers may assist in the risk stratification of patients at an elevated risk of a MACE and subsequently guide further vascular evaluation, specialist referrals, and aggressive medical/surgical management, thereby improving outcomes for patients with CAS.

Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

Risk Factors and Clinical Characteristics of First-ever Ischemic Stroke Caused by ICAS with Leukoaraiosis.

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients.

Machine Learning Detects Symptomatic Plaques in Patients With Carotid Atherosclerosis on CT Angiography.

BACKGROUND: This study aimed to develop and validate a computed tomography angiography based machine learning model that uses plaque composition data and degree of carotid stenosis to detect symptomatic carotid plaques in patients with carotid atherosclerosis. METHODS: The machine learning based model was trained using degree of stenosis and the volumes of 13 computed tomography angiography derived intracarotid plaque subcomponents (eg, lipid, intraplaque hemorrhage, calcium) to identify plaques associated with cerebrovascular events. The model was internally validated through repeated 10-fold cross-validation and tested on a dedicated testing cohort according to discrimination and calibration. RESULTS: This retrospective, single-center study evaluated computed tomography angiography scans of 268 patients with both symptomatic and asymptomatic carotid atherosclerosis (163 for the derivation set and 106 for the testing set) performed between March 2013 and October 2019. The area-under-receiver-operating characteristics curve by machine learning on the testing cohort (0.89) was significantly higher than the areas under the curve of traditional logit analysis based on the degree of stenosis (0.51, P<0.001), presence of intraplaque hemorrhage (0.69, P<0.001), and plaque composition (0.78, P<0.001), respectively. Comparable performance was obtained on internal validation. The identified plaque components and associated cutoff values that were significantly associated with a higher likelihood of symptomatic status after adjustment were the ratio of intraplaque hemorrhage to lipid volume (≥50%, 38.5 [10.1-205.1]; odds ratio, 95% CI) and percentage of intraplaque hemorrhage volume (≥10%, 18.5 [5.7-69.4]; odds ratio, 95% CI). CONCLUSIONS: This study presented an interpretable machine learning model that accurately identifies symptomatic carotid plaques using computed tomography angiography derived plaque composition features, aiding clinical decision-making.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.