Short-Term Double Layer Mesh Stent Patency for Emergent or Elective Carotid Artery Stenting.

Background and Purpose- Novel double layer micromesh stents have recently been introduced for treatment of patients with significant carotid stenosis. Strict evaluation of safety and patency of such novel devices is required both in elective and in emergency interventions. We report a single center experience with double layer mesh stents for carotid artery revascularization. Methods- Consecutive patients who underwent carotid artery stenting with a double layer mesh stent between June 2015 and September 2018 in our tertiary vascular referral center were included. Treatment indications were emergent carotid artery stenting for intracranial or extracranial carotid stenosis in patients undergoing intraarterial thrombectomy for acute ischemic stroke in the anterior circulation, or elective carotid artery stenting for significant symptomatic or asymptomatic stenosis. End points were postprocedural thrombotic stent occlusion and procedural stroke or death. Results- Fifty-four patients were included; 27 were treated for acute stroke with intracranial and extracranial (tandem) lesions and 27 for elective stenting. Follow-up imaging was available for 9/27 (33%) patients with acute stroke, and 19/27 (70%) electively treated patients. Five stent occlusions occurred, of which 2 were symptomatic with clinical deterioration within one day. Another patient deteriorated on postprocedural day one, but imaging of the carotids was not performed, and the stent turned out occluded on the 30-day duplex. All stent occlusions occurred in patients treated for acute stroke. Conclusions- This study suggests that occlusion of novel double layer mesh stents occurs in a considerable proportion of carotid artery stenting procedures performed in the emergency setting for acute stroke, with occlusion-related symptoms in half the cases. Future prospective studies should clarify the role of double layer mesh stents in this high-risk patient population.

A meta-analysis of the effect of stent design on clinical and radiologic outcomes of carotid artery stenting.

OBJECTIVE: Procedural characteristics, including stent design, may influence the outcome of carotid artery stenting (CAS). A thorough comparison of the effect of stent design on outcome of CAS is thus warranted to allow for optimal evidence-based clinical decision making. This study sought to evaluate the effect of stent design on clinical and radiologic outcomes of CAS. METHODS: A systematic search was conducted in MEDLINE, Embase, and Cochrane databases in May 2018. Included were articles reporting on the occurrence of clinical short- and intermediate-term major adverse events (MAEs; any stroke or death) or radiologic adverse events (new ischemic lesions on postprocedural magnetic resonance diffusion-weighted imaging [MR-DWI], restenosis, or stent fracture) in different stent designs used to treat carotid artery stenosis. Random effects models were used to calculate combined overall effect sizes. Metaregression was performed to identify the effect of specific stents on MAE rates. RESULTS: From 2654 unique identified articles, two randomized, controlled trials and 66 cohort studies were eligible for analysis (including 46,728 procedures). Short-term clinical MAE rates were similar for patients treated with open cell vs closed cell or hybrid stents. Use of an Acculink stent was associated with a higher risk of short-term MAE compared with a Wallstent (risk ratio [RR], 1.51; P = .03), as was true for use of Precise stent vs Xact stent (RR, 1.55; P < .001). Intermediate-term clinical MAE rates were similar for open vs closed cell stents. Use of open cell stents predisposed to a 25% higher chance (RR, 1.25; P = .03) of developing postprocedural new ischemic lesions on MR-DWI. No differences were observed in the incidence of restenosis, stent fracture, or intraprocedural hemodynamic depression with respect to different stent design. CONCLUSIONS: Stent design is not associated with short- or intermediate-term clinical MAE rates in patients undergoing CAS. Furthermore, the division in open and closed cell stent design might conceal true differences in single stent efficacy. Nevertheless, open cell stenting resulted in a significantly higher number of subclinical postprocedural new ischemic lesions detected on MR-DWI compared with closed cell stenting. An individualized patient data meta-analysis, including future studies with prospective homogenous study design, is required to adequately correct for known risk factors and to provide definite conclusions with respect to carotid stent design for specific subgroups.

A Clinical Validation Study of Anatomical Risk Scoring for Procedural Stroke in Patients Treated by Carotid Artery Stenting in the International Carotid Stenting Study.

OBJECTIVES: Vascular anatomy of the aortic arch and supra-aortic arteries has been suggested as influencing the risk of carotid artery stenting (CAS). The expert opinion based Delphi anatomical risk (DAR) score was developed to predict difficulty of CAS in relation to procedural stroke risk, and thereby aid patient selection. The aim was to validate the DAR score in the context of a randomised clinical trial. METHODS: In this post hoc analysis of the International Carotid Stenting Study (ICSS), only patients treated by CAS with available pre-procedural CT angiography (CTA) were included. Patients with tortuous anatomy unsuitable for stenting were excluded from ICSS. CTA based vascular anatomy was rated by two independent observers. Every possible combination of anatomy resulted in a risk score, divided in four categories of expected risk (low, < 5.0; low-intermediate, 5.0-5.9; high-intermediate, 6.0-6.9; high, ≥ 7.0). Binomial logistic regression was used to assess the relationship between anatomical risk score and procedural risk of any stroke. Differences between predefined age groups were also assessed. RESULTS: A total of 275 patients were included. Interobserver reliability for all anatomical risk factors was high (κ = 0.76-0.84). In total, 16 strokes (6%) occurred in the procedural period. No significant relationship was observed between the DAR score and risk of procedural stroke, with the risk of stroke being 9% in the high risk vs. 4% in the low risk categories (p = .49). A higher mean DAR score was observed in patients ≥70 years compared with younger patients (4.6 ± 1.5 vs. 3.9 ± 1.4, p < .001), which was mainly explained by higher rates of arch atheroma (44% vs. 20%, p < .001). Prolonged intervention duration was significantly associated with increased stroke risk (11% vs. 4%, p < .04), but not with the DAR score. CONCLUSIONS: No statistically significant association was found between anatomical difficulty, as defined in the DAR score, and procedural stroke risk. However, the small sample size potentially rendered the study underpowered to detect group differences, and confirmation with a larger sample is essential.

Comparability of semiautomatic tortuosity measurements in the carotid artery.

PURPOSE: Increased arterial tortuosity has been suggested as a predisposing factor for carotid artery dissection, which is an important risk factor for development of extracranial carotid artery aneurysms (ECAA). Prior to comparison with non-ECAA controls, the optimal measurement technique should be defined. This study describes the difference between software packages in terms of reproducibility and absolute outcome of arterial tortuosity measurements in ECAA patients. METHODS: CT-angiography analysis was performed on 12 ECAA patients selected from our registry, using four software packages: 3mensio Vascular, TeraRecon, Vital Images, and Aycan OsiriX PRO. The tortuosity index (TI) was calculated from the skull base until the carotid bifurcation and aortic arch, and was defined as the centerline's true length divided by the straight line distance. Intraclass correlation coefficients (ICC) with 95% confidence intervals were calculated to quantify inter- and intra-observer variability within one software package, and differences in measured TI between packages. RESULTS: Inter-observer agreement was nearly perfect for 3mensio, excellent for Vital Images and OsiriX, and substantial for TeraRecon, with ICC 0.99 (0.96-1.0), 0.90 (0.69-0.97), 0.84 (0.53-0.95), and 0.72 (0.28-0.91), respectively. Intra-observer agreement ranged from ICC 1.0 for 3mensio to 0.91 for TeraRecon. Agreements in TI ranged from ICC 0.99 (0.98-1.0) for 3mensio vs. OsiriX, to 0.95 (0.82-0.98) for 3mensio vs. TeraRecon. Median time needed to complete one round of measurements was highest for OsiriX (p = 0.013). CONCLUSIONS: Carotid artery tortuosity measurements are reproducible and comparable between current commercially available software packages, with high intra-observer agreement. Although the reproducibility differed per software packages, all packages scored an acceptable inter-observer agreement.

Editor's Choice - Cerebral Hyperperfusion Syndrome After Carotid Artery Stenting: A Systematic Review and Meta-analysis.

INTRODUCTION: Cerebral hyperperfusion syndrome (CHS) is a preventable cause of stroke after carotid endarterectomy (CEA). There are currently no pooled data available on the incidence of CHS after carotid artery stenting (CAS). The aim of this review was to assess the relevance of CHS in the procedural stroke rate following CAS. METHOD: A systematic search on incidence rates of CHS after CAS was conducted in the MEDLINE, EMBASE, and Cochrane databases in November 2017. A meta-regression analysis was performed on CHS to explain heterogeneity and determine the impact of potential risk factors on observed CHS. The methodological quality of the included studies was assessed using the Cowley criteria. RESULTS: The pooled CHS risk across 33 studies concerning 8731 CAS patients was 4.6% (3.1-6.8%). Stroke occurred in 47% of CHS patients, of which 54% were fatal or disabling. Average time from procedure to symptoms was 12 h (IQR 8-36 h). Impaired cerebrovascular reserve (CVR) was associated with a higher risk of CHS after CAS (RR 5.18; 95% CI 1.0-26.8; p = .049). Symptomatic status was associated with a lower risk of CHS (RR 0.20; 95% CI 0.07-0.59; p = .001). CONCLUSION: CHS is a serious and frequent complication in patients undergoing carotid angioplasty with stenting, and is most likely to occur in the very early post-procedural period. Future studies are encouraged to investigate the effect of intensive haemodynamic monitoring, including blood pressure control and assessment of cerebral blood flow, on the incidence of stroke caused by CHS after CAS.

Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome.

We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1α, IL-6, IL-10, chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy.

Carotid tortuosity is associated with extracranial carotid artery aneurysms.

Background: Tortuous arteries may be associated with carotid dissection. The intima disruption caused by a carotid dissection is a possible cause of extracranial carotid artery aneurysms (ECAAs). The aim was to investigate if carotid tortuosity is also associated with ECAA in patients without presence or history of a carotid artery dissection. Methods: A retrospective case-control study was performed including 35 unilateral ECAA patients (cases) and 105 age- and sex-matched controls. Tortuosity was expressed as tortuosity-index (TI), curvature, and torsion measured on computed tomography angiography (CTA) data in 3Mensio Vascular and MATLAB by two independent investigators. Primary comparison was tortuosity in ipsi- versus contralateral carotid artery within the cohort of ECAA patients. Secondary comparison was tortuosity with ipsilateral carotid arteries in control patients. All observations were assessed on inter- and intra-operator reproducibility. Results: Carotid tortuosity was comparable within the cohort of ECAA patients (Spearman correlation 0.76, P<0.001), yet distinctively higher in comparison with unilateral controls. After adjustment for patient characteristics, presence of ECAA was associated with TI (ß 0.146, 95% CI: 0.100-0.192). All tortuosity observations showed excellent inter- and intra-operator reproducibility. Conclusions: Carotid tortuosity seems to be a risk factor for development of ECAA. Surveillance of individuals with increased carotid tortuosity therefore potentially ensures prompt diagnosis and treatment of ECAA. However, future research should investigate if persons with an increased tortuosity do indeed develop ECAA.

(In)comparability of Carotid Artery Stent Characteristics: A Systematic Review on Assessment and Comparison with Manufacturer Data.

PURPOSE: Carotid stent (CS) characteristics, such as radial force, scaffolding and flexibility, are continuously modified by stent manufacturers aiming to improve stent performance. Since manufacturers' definitions and assessment methods are not disclosed, it is unknown how characteristics of different CSs relate to each other or to published literature. We examined in vitro methodological techniques used to measure CS characteristics and assessed comparability between published papers and outcomes as provided by the manufacturers. METHODS: A systematic review was conducted in MEDLINE, Embase, Cochrane, and Scopus databases. Studies reporting on in vitro investigations of predefined characteristics of CS used in current everyday clinical practice were included. The predefined characteristics were radial force, scaffolding, flexibility, foreshortening, side-branch preservation and visibility. Eight manufacturers of 10 currently used CS were contacted and data on the predefined device characteristics was requested. RESULTS: 12 published articles were included and six stent manufacturers provided data on six stents (two refused to share data). Used methodologies to measure stent characteristics in published literature and manufacturer data varied greatly for all included characteristics except foreshortening. The number of different units of measurement to express outcomes ranged from two for foreshortening to six for radial force. CONCLUSION: A variety of methodologies and outcome measures is used to quantify CS characteristics, which hampers comparisons between published studies and manufacturer data. Future studies are encouraged to synchronize methodologies and outcome measures. Manufacturers are encouraged up to increase transparency of applied testing methodologies and outcomes.

Inflammatory mediators in human epilepsy: A systematic review and meta-analysis.

BACKGROUND: Accumulating evidence suggests a role for inflammation in the pathophysiology of epilepsy. METHODS: We performed a systematic review and meta-analysis of studies that investigated inflammatory mediators in human epilepsy. Studies reporting on inflammatory mediators in serum, cerebrospinal fluid or brain tissue of epilepsy patients were included. Studies comparing patients to controls were included in a meta-analysis. RESULTS: 66 articles reporting on 1934 patients were included. IL-1ra, IL-1ß, IL-6, IL-10, IFN-γ and TNF-α were the most extensively investigated proteins. Elevated levels for IL-1ra, IL-1ß, IL-6 and CXCL8/IL-8 were reported in several different epilepsy etiologies and media, while other proteins were specifically increased for one etiology. IL-1α, IL-7 and IL-13, as well as the chemokines CCL2-5, -19 and -22, were increased exclusively in brain tissue. In an aggregate meta-analysis, we found significantly different protein levels for serum IL-6, IL-17 and CSF IL-1ß and IL-10. CONCLUSION: Inflammatory pathways are involved in epilepsy. Future studies may further clarify their role, and prove potential of targeted anti-inflammatory treatment.