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BACKGROUND: Patients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value >50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making. OBJECTIVES: The PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging. METHODS: The authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score. RESULTS: During 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78). CONCLUSIONS: IPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025). ispartof: JACC-CARDIOVASCULAR IMAGING vol:15 issue:10 pages:1715-1726 ispartof: location:United States status: published

Mit Hilfe der evozierten Potenziale und der magnetisch evozierten motorischen Potenziale können verlängerte Latenzen zentraler Leitungsbahnen und peripherer Nerven nachgewiesen oder ausgeschlossen werden. Somit können Symptome objektiviert und quantifiziert sowie Läsionen lokalisiert werden. In diesem Beitrag werden Durchführung und Indikationen der einzelnen Modalitäten zusammengefasst und Neuerungen berichtet.

Thoraco-abdominal aneurysm (TAA) repair carries a significant risk of spinal cord infarction. The latter results from irreversible changes in the spinal cord arterial network, e.g., sacrifice of the segmental arteries. Intra-operative neurophysiology with somatosensory and especially motor evoked potential (SEP and MEP respectively) monitoring, has emerged as an effective tool to assess the efficiency of the collateral blood flow, detect reversible spinal cord ischemia and guide the peri-operative multidisciplinary management to prevent postoperative paraplegia. The main roles of such monitoring include diagnosis of spinal cord vs peripheral limb ischemia, titration of mean arterial pressure during aortic clamping, the guidance of selective re-implantation of critical segmental arteries, and management of hemodynamics in the immediate postoperative period. In addition, manipulation of the aortic arch and proximal descending aorta, adds the risk of cerebral infarction from both low flow state and/or thromboembolic events. As such, EEG monitoring may be a useful add-on for either assessment of the efficiency of cerebral cooling as a neuroprotective method and/or for detection and treatment of reversible cerebral ischemia. This chapter presents the multimodality approach to open TAA monitoring as a versatile tool for the prevention of devastating postoperative neurologic deficits.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Aims/hypothesis We aimed to examine associations of cardiometabolic risk factors, and (pre)diabetes, with (sensorimotor) peripheral nerve function. Methods In 2401 adults (aged 40–75 years) we previously determined fasting glucose, HbA1c, triacylglycerol, HDL- and LDL-cholesterol, inflammation, waist circumference, blood pressure, smoking, glucose metabolism status (by OGTT) and medication use. Using nerve conduction tests, we measured compound muscle action potential, sensory nerve action potential amplitudes and nerve conduction velocities (NCVs) of the peroneal, tibial and sural nerves. In addition, we measured vibration perception threshold (VPT) of the hallux and assessed neuropathic pain using the DN4 interview. We assessed cross-sectional associations of risk factors with nerve function (using linear regression) and neuropathic pain (using logistic regression). Associations were adjusted for potential confounders and for each other risk factor. Associations from linear regression were presented as standardised regression coefficients (β) and 95% CIs in order to compare the magnitudes of observed associations between all risk factors and outcomes. Results Hyperglycaemia (fasting glucose or HbA1c) was associated with worse sensorimotor nerve function for all six outcome measures, with associations of strongest magnitude for motor peroneal and tibial NCV, βfasting glucose = −0.17 SD (−0.21, −0.13) and βfasting glucose = −0.18 SD (−0.23, −0.14), respectively. Hyperglycaemia was also associated with higher VPT and neuropathic pain. Larger waist circumference was associated with worse sural nerve function and higher VPT. Triacylglycerol, HDL- and LDL-cholesterol, and blood pressure were not associated with worse nerve function; however, antihypertensive medication usage (suggestive of history of exposure to hypertension) was associated with worse peroneal compound muscle action potential amplitude and NCV. Smoking was associated with worse nerve function, higher VPT and higher risk for neuropathic pain. Inflammation was associated with worse nerve function and higher VPT, but only in those with type 2 diabetes. Type 2 diabetes and, to a lesser extent, prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were associated with worse nerve function, higher VPT and neuropathic pain (p for trend Conclusions/interpretation Hyperglycaemia (including the non-diabetic range) was most consistently associated with early-stage nerve damage. Nonetheless, larger waist circumference, inflammation, history of hypertension and smoking may also independently contribute to worse nerve function.

Background: Despite all efforts, spinal cord ischemia (SCI) is a relevant and feared complication after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Besides the established correlation of motor evoked potentials (MEPs) and SCI, the usage of biomarkers for early detection of SCI intraoperatively and postoperatively after TAAA surgery is scarcely described in literature.Methods: The methods include retrospective assessment of 33 patients (48.48% male) undergoing open and endovascular TAAA repair between January 2017 and January 2018. Levels of the biomarkers neurone-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100 B were correlated with a decrease of the amplitude of the MEPs of more than 50%, indicating SCI. Linear mixed models were applied to test for differences in the biomarker levels between open and endovascular surgery and between different times of measurement. Post hoc analyses were performed using Tukey's multiple comparisons test. Logistic regression models were used to investigate the association between GFAP, NSE, and S100 B levels at different times and a significant decrease in MEP or in-hospital mortality.Results: Altogether, 19 patients were treated by endovascular repair; 14 patients were treated by open repair; 5 patients were treated because of a type I TAAA; 7 received treatment because of a type II TAAA; 7, 10, and 4 patients received type III, IV, or V TAAA repair, respectively. In-hospital mortality was 18.18% (n = 6); 5 of these patients were treated because of symptomatic TAAA. MEP decrease could be observed in 18 cases (54.5%), with 16 (48.4%) recovering during the intervention. SCI could be observed in 9.09% (n = 3), 2 endovascular repairs leading to paraplegia and one open repair leading to paraparesis. All biomarkers showed increasing levels over time, with no statistically significant difference between open and endovascular repair. The difference in NSE and S100 B levels between the different times of measurements was statistically significant (P < 0.0001, P = 0.0017, respectively). In a univariable logistic regression analysis, no correlation with the end points "significant decrease in MEP'' or "in-hospital mortality'' was observed for any of the assessed biomarkers.Conclusions: SCI-related biomarkers, namely NSE and S100 B, show a relevant increase directly after open and endovascular TAAA surgery, while no clear association between these biomarker levels and an intraoperatively measurable indicator for SCI could be observed.

The Esaote MyLab70 ultrasound system has been extensively used to evaluate arterial properties. Since it is reaching end-of-service-life, ongoing studies are forced to seek an alternative, with some opting for the Esaote MyLabOne. Biases might exist between the two systems, which, if uncorrected, could potentially lead to the misinterpretation of results. This study aims to evaluate a potential bias between the two devices. Moreover, by comparing two identical MyLabOne systems, this study also aims to investigate whether biases estimated between the MyLabOne and MyLab70 employed in this study could be generalized to any other pair of similar scanners. Using a phantom set-up, we performed n = 60 measurements to compare MyLab70 to MyLabOne and n = 40 measurements to compare the two MyLabOne systems. Comparisons were performed to measure diameter, wall thickness, and distension. Both comparisons led to significant biases for the diameter (relative bias: −0.27% and −0.30% for the inter- and intra-scanner model, respectively, p < 0.05) and wall thickness (relative bias: 0.38% and −1.23% for inter- and intra-scanner model, respectively p < 0.05), but not for distension (relative bias: 0.48% and −0.12% for inter- and intra-scanner model, respectively, p > 0.05). The biases estimated here cannot be generalized to any other pair of similar scanners. Therefore, longitudinal studies with large sample sizes switching between scanners should perform a preliminary comparison to evaluate potential biases between their devices. Furthermore, caution is warranted when using biases reported in similar comparative studies. Further work should evaluate the presence and relevance of similar biases in human data.

Patients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making.The PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging.The authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score.During 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78).IPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025).

Background and purpose Reported cutoff values of the optic nerve sheath diameter (ONSD) for the diagnosis of elevated intracranial pressure (ICP) are inconsistent. This hampers ONSD as a possible noninvasive bedside monitoring tool for ICP. Because the influence of methodological differences on variations in cutoff values is unknown, we performed a narrative review to identify discrepancies in ONSD assessment methodologies and to investigate their effect on reported ONSD values. Methods We used a structured and quantitative approach in which each ONSD methodology found in the reviewed articles was categorized based on the characteristic appearance of the ultrasound images and ultrasound marker placement. Subsequently, we investigated the influence of the different methodologies on ONSD values by organizing the ONSDs with respect to these categories. Results In a total of 63 eligible articles, we could determine the applied ONSD assessment methodology. Reported ultrasound images either showed the optic nerve and its sheath as a dark region with hyperechoic striped band at its edges or as a single dark region surrounded by lighter retrobulbar fat. Four different ultrasound marker positions were used to delineate the optic nerve sheath, which resulted in different ONSD values and more importantly, different sensitivities to changes in ICP. Conclusions Based on our observations, we recommend to place ultrasound markers at the outer edges of the hyperechoic striped bands or at the transitions from the single dark region to the hyperechoic retrobulbar fat because these locations yielded the highest sensitivity of ONSD measurements for increased ICP.

BACKGROUND AND PURPOSE The optic nerve sheath diameter (ONSD) is a promising surrogate marker for the detection of raised intracranial pressure (ICP). However, inconsistencies in manual ONSD assessment are thought to affect ONSD and the corresponding ONSD cutoff values for the diagnosis of elevated ICP, hereby hampering the full potential of ONSD. In this study, we developed an image intensity-invariant algorithm to automatically estimate ONSD from B-mode ultrasound images at multiple depths.METHODS The outcomes of the algorithm were validated against manual ONSD measurements by two human experts. Each expert analyzed the images twice (M1 and M2) in unknown order.RESULTS The algorithm proved capable of segmenting the ONSD in 39 of 42 images, hereby showing mean differences of -.08 +/- .45 and -.05 +/- .41 mm compared to averaged ONSD values (M1 + M2/2) of Operator 1 and Operator 2, respectively, whereas the mean difference between the two experts was .03 +/- .26 mm. Moreover, differences between algorithm-derived and expert-derived ONSD values were found to be much smaller than the 1 mm difference that is expected between patients with normal and elevated ICP, making it likely that our algorithm can distinguish between these patient groups.CONCLUSIONS Our algorithm has the potential to improve the accuracy of ONSD as a surrogate marker for elevated ICP because it has no intrinsic variability. However, future research should be performed to validate if the algorithm does indeed result in more accurate noninvasive ICP predictions.

IntroductionDistal sensorimotor polyneuropathy (DSPN) is common in people with diabetes but is also found in pre-diabetes. Peripheral nerve myelin damage, which can be assessed by reduced nerve conduction velocity (NCV), is an essential feature of DSPN. Emerging evidence indicates that the development of DSPN may involve the activation of the immune system. However, available studies have mainly investigated circulating immune mediators, whereas the role of immune cells remains unclear. Therefore, we aimed to test whether leukocyte subsets are associated with NCV.Research design and methodsThis cross-sectional study analyzed data from 850 individuals (of whom 252 and 118 had type 2 diabetes and pre-diabetes, respectively) of the Maastricht Study. NCV was measured in the peroneal and tibial motor nerves and the sural sensory nerve and summed to calculate a standardized NCV sum score. Associations between percentages of leukocyte subsets and NCV sum scores were estimated using linear regression models adjusted for demographic, lifestyle, metabolic and clinical covariates.ResultsAfter adjustment for covariates, higher percentages of basophils and CD4+ T cells were associated with lower NCV (p=0.014 and p=0.005, respectively). The percentage of CD8+ T cells was positively associated with NCV (p=0.022). These associations were not modified by glucose metabolism status (all pinteraction >0.05). No associations were found for monocytes, eosinophils, neutrophils, lymphocytes, total T cells, Treg cells and B cells.ConclusionsThe associations of basophils, CD4+ and CD8+ T cells with NCV suggest that cell types from both innate and adaptive immunity may be implicated in the development of DSPN.

Nutrients 13(3), 994 (2021). doi:10.3390/nu13030994 special issue: "Clinical Nutrition / Editorial Board : Ina Bergheim, Section Editor-in-Chief", Published by MDPI, Basel

Die operative Therapie eines Aneurysmas der Aorta birgt das Risiko einer Ruckenmarksischamie und moglicherweise einer postoperativen Paraplegie. Die funktionelle Integritat des Ruckenmarks kann peroperativ mit Hilfe des sog. MEP (motorisch evozierte Potentiale)-Monitorings uberwacht werden, wobei die An- oder Abwesenheit der MEPs eine ausgezeichnete Korrelation mit dem postoperativen neurologischen Status aufweist. In den meisten Fallen ist es moglich, durch eine Verbesserung der spinalen Durchblutung auf abweichende Befunde des MEP-Monitorings zu reagieren und damit einen wichtigen Beitrag zur Paraplegieprophylaxe zu leisten. Wir fuhren diese Form des Neuromonitorings in einem telemedizinischen Setting durch, wobei sich der die Messungen beurteilende Neurophysiologe an zentraler Stelle befindet, die Operationen jedoch in 5 verschiedenen Kliniken stattfinden, auch uber Landesgrenzen hinweg. Vor Ort werden die MEPs durch nichtarztliches Personal – das in standigem Kontakt zum Arzteteam im OP und zum Neurophysiologen steht – gemessen. Diese Herangehensweise ermoglicht ein komplexes und klinisch relevantes Neuromonitoring bei gleichzeitig maximaler Kosteneffektivitat.

ObjectiveRecent studies have revealed the importance of the gut brain axis in the development of Parkinson’s disease (PD). It has also been suggested that the cross-sectional area (CSA) of the vagus nerve can be used in the diagnosis of PD. Here, we hypothesize that the CSA of the vagus nerve is decreased in PD patients compared to control subjects.MethodsIn this study we measured the CSA of the vagus nerve on both sides in 31 patients with PD and 51 healthy controls at the level of the common carotid artery using high-resolution ultrasound.ResultsThe CSA of the vagus nerve was not reduced in PD patients compared to controls (p = 0.391. The mean CSA of the left vagus nerve was significantly smaller than the right (p < 0.001). There was no significant correlation between age, gender and autonomic symptoms with the CSA of the left (p = 0.128) and right vagus nerve (p = 0.166).ConclusionThese findings show that the CSA of the vagus nerve using ultrasonography is not a reliable diagnostic tool in the diagnosis of PD.HighlightsThe cross-sectional area of the vagus nerve is not decreased in Parkinson disease patients.The cross-sectional area of the vagus nerve does not correlate with autonomic symptoms.Measurement of the vagus nerve cross-sectional area has a high inter-observer correlation.

Background: During descending aortic repair, critically decreased blood flow to the myelum can result in ischemic spinal cord injury and transient or permanent paraplegia. Assessment of motor evoked potentials (MEPs) has been shown to be a valuable tool which allows to detect spinal cord ischemia (SCI) intraoperatively within a therapeutic window suitable to prevent progression to paraparesis or paraplegia. MEP monitoring is not feasible during postoperative care in the awakening patient. Therefore, ancillary techniques to monitor integrity of spinal cord function are needed to detect delayed spinal cord ischemia. Objective: The purpose of this study is to evaluate whether assessment of long loop reflexes (LLR; F-waves) and paraspinal muscle oximetry using Near-Infrared Spectroscopy (NIRS) are feasible and valid in detecting delayed SCI. Methods: We aim to include patients from three tertiary referral centers undergoing aortic repair with MEP monitoring in this study.F-wave measurements and paraspinal NIRS oximetry will be operated intra- and postoperatively. Measurement characteristics and feasibility will be assessed in the first 25 patients. Subsequently, a second cohort of 75 patients will be investigated to determine the sensitivity and specificity of F-waves and NIRS in detecting perioperative SCI. In this context for the MEP group SCI is defined intraoperatively as significant MEP changes and postoperatively as newly developed paraplegia. Conclusions: A clinical study design and protocol is proposed to assess if F-waves and/or NIRS-based paraspinal oximetry are feasible and valid in detecting and monitoring for occurrences of delayed SCI. Keywords: Spinal cord ischemia, Neurophysiological monitoring techniques, NIRS oximetry, Descending aortic repair, Thoracoabdominal aortic aneurysm repair

Background: Currently, continuous electroencephalographic monitoring (cEEG) is the only available diagnostic tool for continuous monitoring of brain function in intensive care unit (ICU) patients. Yet, the exact relevance of routinely applied ICU cEEG remains unclear, and information on the implementation of cEEG, especially in Europe, is scarce. This study explores current practices of cEEG in adult Dutch ICU departments focusing on organizational and operational factors, development over time and factors perceived relevant for abstaining its use.Methods: A national survey on cEEG in adults among the neurology and adult intensive care departments of all Dutch hospitals (n=82) was performed.Results: The overall institutional response rate was 78%. ICU cEEG is increasingly used in the Netherlands (in 37% of all hospitals in 2016 versus in 21% in 2008). Currently in 88% of university, 55% of teaching and 14% of general hospitals use ICU cEEG. Reasons for not performing cEEG are diverse, including perceived non-feasibility and lack of data on the effect of cEEG use on patient outcome. Mostly, ICU cEEG is used for non-convulsive seizures or status epilepticus and prognostication. However, cEEG is never or rarely used for monitoring cerebral ischemia and raised intracranial pressure in traumatic brain injury. Review and reporting practices differ considerably between hospitals. Nearly all hospitals perform non-continuous review of cEEG traces. Methods for moving toward continuous review of cEEG traces are available but infrequently used in practice.Conclusions: cEEG is increasingly used in Dutch ICUs. However, cEEG practices vastly differ between hospitals. Future research should focus on uniform cEEG practices including unambiguous EEG interpretation to facilitate collaborative research on cEEG, aiming to provide improved standard patient care and robust data on the impact of cEEG use on patient outcome.

Purpose To assess the diagnostic value of automatic embolus detection software (AEDS) in transcranial Doppler (TCD) monitoring for the detection of solid microemboli in patients at risk for perioperative stroke during carotid endarterectomy (CEA). Materials and Methods In 50 patients undergoing CEA, perioperative TCD registration was recorded. All recorded events, identified and saved by the AEDS, were analyzed off-line doubly by two human experts (HEs) within a time frame of > 4 months. The inter- and intraobserver variability was assessed. The overall agreement with the HEs, the sensitivity, specificity, negative and positive predictive values (NPV and PPV) of the AEDS were computed for different cut-offs (patient displaying perioperative 5, 10, 20, 25, or 50 microemboli). Results 77 233 events were analyzed. The inter- and intraobserver variability was good (min κ = 0.72, max κ = 0.79). AEDS and the HEs identified 760 and 470 solid emboli, respectively. The agreement between AEDS and the HEs for solid emboli detection was poor (κ = 0.24, SE = 0.016). The specificity and NPV were high (99.2 % and 99.6 %) but the sensitivity and PPV were low (30.6 % and 19.8 %). Applying a threshold of > 20 microemboli resulted in the best sensitivity (100.0 %), specificity (84.4 %), PPV (42.7 %), NPV (100.0 %) and area under the curve (0.898). However, 58.3 % of the patients were false positive as classified by AEDS. Conclusion In this validation cohort, AEDS has insufficient agreement with HEs in the identification of solid emboli. AEDS and HEs disagree with respect to the identification of specific patients at risk. Therefore, AEDS cannot be used as a standalone system to identify patients at risk for perioperative stroke during CEA.

Purpose To assess parameter agreement of volume transfer coefficient (Ktrans) between two vascular regions and to study the correlation with microvessel density on histology. The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter Ktrans is frequently used to study atherosclerotic plaque microvasculature. Ktrans has been reported using different descriptive statistics (mean, median, 75th percentile) either for the whole vessel wall or the adventitia in previous studies. Materials and Methods DCE-MRI parameter agreement was analyzed in 110 symptomatic patients with ≥2 mm carotid plaque that underwent a 3T carotid DCE-MRI examination. Ktrans was estimated in the entire vessel wall and adventitia. Twenty-three patients underwent carotid endarterectomy and were used for comparison with histological quantification of microvessel density of the plaque using CD31 immunohistochemistry. DCE-MRI parameters in the vessel wall regions were compared using Pearson's correlation coefficient, Bland–Altman analysis, and a two-sided paired samples t-test. Correlation of the DCE-MRI parameters with histology was studied using the Pearson's correlation coefficient. Results Median adventitial Ktrans was 5% higher (P = 0.003) than entire vessel wall Ktrans, with no differences for other descriptive statistics. Vessel wall and adventitial Ktrans showed similar moderately strong correlations with plaque microvessel density on histology (Pearson's ρ: 0.59–0.65 [P < 0.003] and 0.52–0.64 [P < 0.011], respectively). Conclusion The similar moderately strong correlations for vessel wall and adventitial Ktrans with microvessel density on histology suggested that both regions reflected plaque microvessel density. Care should to be taken when comparing absolute values between studies. Future studies incorporating thresholds for risk stratification need to agree upon standardization of DCE-MRI parameters. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1053–1059.

Variations in systemic properties of the arterial tree, such as aging-induced vessel stiffness, can alter the shape of pressure and flow waveforms. As a consequence, the hemodynamics around a cerebral aneurysm change, and therefore, also the corresponding in- and outlet boundary conditions (BCs) used for three-dimensional (3D) calculations of hemodynamic indices. In this study, we investigate the effects of variations in systemic properties on wall shear stress (WSS) indices of a cerebral aneurysm. We created a virtual patient database by varying systemic properties within physiological ranges. BCs for 3D-CFD simulations were derived using a pulse wave propagation model for each realization of the virtual database. WSS indices were derived from the 3D simulations and their variabilities quantified. Variations in BCs, caused by changes in systemic properties, yielded variabilities in the WSS indices that were of the same order of magnitude as differences in these WSS indices between ruptured and unruptured aneurysms. Sensitivity analysis showed that the systemic properties impacted both in- and outlet BCs simultaneously and altered the WSS indices. We conclude that the influence of variations in patient-specific systemic properties on WSS indices should be evaluated when using WSS indices in multidisciplinary rupture prediction models.

Contains fulltext : 208975.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2.45 (1.82-3.29) for intracranial haemorrhage and 1.23 (1.08-1.40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4.55 [95% CI 3.08-6.72] for intracranial haemorrhage vs 1.47 [1.19-1.80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5.52 [3.36-9.05] vs 1.43 [1.07-1.91]; and for >/=20 cerebral microbleeds, aHR 8.61 [4.69-15.81] vs 1.86 [1.23-1.82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for >/=20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

Background Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. The objective of the present study is to investigate whether there is a difference in plaque microvasculature (the volume transfer coefficient K trans ) between the ipsilateral symptomatic and contralateral asymptomatic carotid plaque using noninvasive dynamic contrast‐enhanced magnetic resonance imaging. Methods and Results Eighty‐eight patients with recent transient ischemic attack or ischemic stroke and ipsilateral >2 mm carotid plaque underwent 3 T magnetic resonance imaging to identify plaque components and to determine characteristics of plaque microvasculature. The volume transfer coefficient K trans , indicative for microvascular density, flow, and permeability, was calculated for the ipsilateral and asymptomatic plaque, using a pharmacokinetic model (Patlak). Presence of a lipid‐rich necrotic core, intraplaque hemorrhage, and a thin and/or ruptured fibrous cap was assessed on multisequence magnetic resonance imaging . We found significantly lower K trans in the symptomatic carotid plaque compared with the asymptomatic side (0.057±0.002 min −1 versus 0.062±0.002 min −1 ; P =0.033). There was an increased number of slices with intraplaque hemorrhage (0.9±1.6 versus 0.3±0.8, P =0.002) and lipid‐rich necrotic core (1.4±1.9 versus 0.8±1.4, P =0.016) and a higher prevalence of plaques with a thin and/or ruptured fibrous cap (32% versus 17%, P =0.023) at the symptomatic side. Conclusions K trans was significantly lower in symptomatic carotid plaques, indicative for a decrease of plaque microvasculature in symptomatic plaques. This could be related to a larger amount of necrotic tissue in symptomatic plaques. Clinical Trial Registration URL : http://www.clinicaltrials.gov.uk . Unique identifier: NCT 01208025.

Spinal cord ischemia is one of the most dreadful complications of thoracic and thoracoabdominal aortic surgery. The complex mechanisms of spinal cord perfusion under iatrogenic circumstances, such as surgery, are still not fully unraveled. Neuromonitoring during open and endovascular aortic surgery aims at assessing perioperative spinal cord function, allowing corrective measures in case of compromised spinal cord perfusion and thus reducing the incidence of postoperative spinal cord ischemia. The technique of motor evoked potentials is a reliable and highly accurate method to evaluate spinal cord integrity during thoracic and thoracoabdominal aortic repair.

The presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events. However, the mechanisms leading to IPH are not fully understood. The dominant view is that IPH is caused by leakage of erythrocytes from immature microvessels. The aim of the present study was to investigate whether there is an association between atherosclerotic plaque microvasculature and presence of IPH in a relatively large prospective cohort study of patients with symptomatic carotid plaque. One hundred and thirty-two symptomatic patients with ≥2 mm carotid plaque underwent cardiovascular magnetic resonance (CMR) of the symptomatic carotid plaque for detection of IPH and dynamic contrast-enhanced (DCE)-CMR for assessment of plaque microvasculature. Ktrans, an indicator of microvascular flow, density and leakiness, was estimated using pharmacokinetic modelling in the vessel wall and adventitia. Statistical analysis was performed using an independent samples T-test and binary logistic regression, correcting for clinical risk factors. A decreased vessel wall Ktrans was found for IPH positive patients (0.051 ± 0.011 min− 1 versus 0.058 ± 0.017 min− 1, p = 0.001). No significant difference in adventitial Ktrans was found in patients with and without IPH (0.057 ± 0.012 min− 1 and 0.057 ± 0.018 min− 1, respectively). Histological analysis in a subgroup of patients that underwent carotid endarterectomy demonstrated no significant difference in relative microvessel density between plaques without IPH (n = 8) and plaques with IPH (n = 15) (0.000333 ± 0.0000707 vs. and 0.000289 ± 0.0000439, p = 0.585). A reduced vessel wall Ktrans is found in the presence of IPH. Thus, we did not find a positive association between plaque microvasculature and IPH several weeks after a cerebrovascular event. Not only leaky plaque microvessels, but additional factors may contribute to IPH development. NCT01208025 . Registration date September 23, 2010. Retrospectively registered (first inclusion September 21, 2010). NCT01709045 , date of registration October 17, 2012. Retrospectively registered (first inclusion August 23, 2011).

Objective: Rupture of atherosclerotic plaques is ultimately a biomechanical event. We aim to develop and validate a novel method using ultrasound radiofrequency (RF) measurements to determine intraplaque inhomogeneities in the strain distribution with a high axial resolution which may identify rupture-prone plaques. Methods: Ultrasound examinations were performed on CCAs and ICAs of 17 patients with recent stroke/TIA and 5 asymptomatic patients (39 CCAs and ICAs). Strain distribution was computed from RF data with a depth resolution

Objective: To assess whether migraine in the general population is associated with increased risk of systemic right-to-left shunts (RLS) and whether RLS are associated with increased prevalence of brain infarcts and persistent recurrence of migraine attacks at older age. Methods: Brain MRI and transcranial Doppler with air contrast in 166 unselected migraineurs (mean age ± SD 56 ± 7.7 years; 70% women; n = 96 migraine with aura) and 69 controls (mean age ± SD 55 ± 7.6 years; 65% women) from the general population. Results: Participants with migraine with aura more frequently had Valsalva-induced RLS (60%), in particular large-sized, compared to controls (42%; odds ratio [OR] 2.1; 95% confidence interval [CI] 1.1–3.9; p = 0.02) and participants with migraine without aura (40%; OR 2.3; 95% CI 1.2–4.3; p = 0.01). They also more frequently had spontaneous RLS (35%) than participants with migraine without aura (17%; OR 2.6; 95% CI 1.3–5.6; p = 0.01) but not compared to controls (26%; OR 1.6; 95% CI 0.8–3.1; p = 0.2). Participants with migraine with aura and spontaneous RLS more frequently had persistent migraine activity (85%) than participants with migraine without spontaneous RLS (63%; OR 3.4; 95% CI 1.2–10.1; p = 0.03). Nine percent of participants with RLS had silent posterior circulation infarcts compared to 3% of participants without RLS (OR 2.8; 95% CI 0.9–9.3; p = 0.08), independent of migraine status. RLS were not associated with white matter lesions. Conclusions: RLS are more prevalent in migraineurs with aura but do not explain the increased prevalence of silent posterior circulation infarcts or white matter lesions in migraineurs. Spontaneous RLS are associated with persistent migraine.

A long-standing concern has been whether epilepsy contributes to cognitive decline or so-called 'epileptic dementia'. Although global cognitive decline is generally reported in the context of chronic refractory epilepsy, it is largely unknown what percentage of patients is at risk for decline. This review is focused on the identification of risk factors and characterization of aberrant cognitive trajectories in epilepsy. Evidence is found that the cognitive trajectory of patients with epilepsy over time differs from processes of cognitive ageing in healthy people, especially in adulthood-onset epilepsy. Cognitive deterioration in these patients seems to develop in a 'second hit model' and occurs when epilepsy hits on a brain that is already vulnerable or vice versa when comorbid problems develop in a person with epilepsy. Processes of ageing may be accelerated due to loss of brain plasticity and cognitive reserve capacity for which we coin the term 'accelerated cognitive ageing'. We believe that the concept of accelerated cognitive ageing can be helpful in providing a framework understanding global cognitive deterioration in epilepsy.

Item does not contain fulltext Local arterial stiffness can be assessed with high accuracy and precision by measuring arterial distension on the basis of phase tracking of radiofrequency ultrasound signals acquired at a high frame rate. However, in clinical practice, B-mode ultrasound registrations are made at a low frame rate (20-50 Hz). We compared the accuracy and intra-subject precision of edge tracking and phase tracking distension in symptomatic carotid artery patients. B-mode ultrasound recordings (40 mm, 37 fps) and radiofrequency recordings (31 lines covering 29 mm, 300 fps) were acquired from the left common carotid artery of 30 patients (aged 45-88 y) with recent cerebrovascular events. To extract the distension, semi-automatic echo edge and phase tracking algorithms were applied to B-mode and radiofrequency recordings, respectively. Both methods exhibited a similar intra-subject precision for distension (standard deviation = 44 mum and 47 mum, p = 0.66) and mean distension (difference: -6 +/- 69 mum, p = 0.67). Intra-subject distension inhomogeneity tends to be larger for edge tracking (difference: 15 +/- 35 mum, p = 0.04). Standard B-mode scanners are suitable for measuring local artery characteristics in symptomatic carotid artery patients with good precision and accuracy.

Background. Patients with Parkinson’s disease (PD) have a high risk of cognitive problems.Objective. This study assesses whether abnormal echogenicity of the substantia nigra (SN) and raphe nuclei (RN) and the diameter of third ventricle are markers of cognitive impairment in patients with PD and other forms of parkinsonism.Methods. 126 outpatients with early signs of parkinsonism underwent transcranial sonography (TCS). The scales for the outcome of Parkinson’s disease cognition (SCOPA-COG) were used as cognitive measure. Definite neurological diagnosis was established after two-year follow-up.Results. One-third of the patients with PD and half of those with APS had signs of cognitive impairment. The echogenicity of the SN was not related to cognitive impairment. The diameter of the third ventricle was significantly larger in PD patients with cognitive impairment compared to those without. In patients with APS we found a significantly higher frequency of hypoechogenic RN in patients with cognitive problems.Conclusions. Cognitive impairment is already present in a substantial proportion of patients with PD and APS at first referral. In patients with APS the frequency of hypoechogenic RN points to the direction of other pathophysiology with more emphasis on deficits in the serotonergic neurotransmitter system. The larger diameter of the third ventricle in PD patients with cognitive impairment may reflect Alzheimer like brain atrophy, as has been reported in earlier studies.

To properly assess morphologic and dynamic parameters of arteries and plaques, we propose the concept of orthogonal distance measurements, that is, measurements made perpendicular to the local lumen axis rather than along the ultrasound beam (vertical direction for a linear array). The aim of this study was to compare orthogonal and vertical artery and lumen diameters at the site of a plaque in the common carotid artery (CCA). Moreover, we investigated the interrelationship of orthogonal diameters and plaque size and the association of artery parameters with plaque echogenicity. In 29 patients, we acquired a longitudinal B-mode ultrasound recording of plaques at the posterior CCAwall. After semi-automatic segmentation of end-diastolic frames, diameters were extracted orthogonally along the lumen axis. To establish inter-observer variability of diameters obtained at the location of maximal plaque thickness, a second observer repeated the analysis (subset N = 21). Orthogonal adventitia-adventitia and lumen diameters could be determined with good precision (coefficient of variation: 1%-5%. However, the precision of the change in lumen diameter from diastole to systole (distension) at the site of the plaque was poor (21%-50%). The orthogonal lumen diameter was significantly smaller than the vertical lumen diameter (p < 0.001). Surprisingly, the plaques did not cause outward remodeling, that is, a local increase in adventitia-adventitia distance at the site of the plaque. The intra- and inter-observer precision of diastolic-systolic plaque compression was poor and of the same order as the standard deviation of plaque compression. The orthogonal relative lumen distension was significantly lower for echogenic plaques, indicating a higher stiffness, than for echolucent plaques (p < 0.01). In conclusion, we illustrated the feasibility of extracting orthogonal CCA and plaque dimensions, albeit that the proposed approach is inadequate to quantify plaque compression. (E-mail: werner.mess@mumc.nl) (c) 2018 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Journal of Vascular Surgery Cases and Innovative Techniques 4(1), 54-57 (2018). doi:10.1016/j.jvscit.2017.12.004, Published by Elsevir

Background: Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. Methods: A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCE-MRI and the pharmacokinetic modeling parameter Ktrans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. Results: The 75th percentile adventitial (OR 1.97, 95% CI 1.18-3.29) Ktrans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. Conclusions: This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether Ktrans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events.

Contains fulltext : 175960.pdf (Publisher’s version ) (Open Access) BACKGROUND: Mean or maximal intima-media thickness (IMT) is commonly used as surrogate endpoint in intervention studies. However, the effect of normalization by surrounding or median IMT or by diameter is unknown. In addition, it is unclear whether IMT inhomogeneity is a useful predictor beyond common wall parameters like maximal wall thickness, either absolute or normalized to IMT or lumen size. We investigated the interrelationship of common carotid artery (CCA) thickness parameters and their association with the ipsilateral internal carotid artery (ICA) stenosis degree. METHODS: CCA thickness parameters were extracted by edge detection applied to ultrasound B-mode recordings of 240 patients. Degree of ICA stenosis was determined from CT angiography. RESULTS: Normalization of maximal CCA wall thickness to median IMT leads to large variations. Higher CCA thickness parameter values are associated with a higher degree of ipsilateral ICA stenosis (p < 0.001), though IMT inhomogeneity does not provide extra information. When the ratio of wall thickness and diameter instead of absolute maximal wall thickness is used as risk marker for having moderate ipsilateral ICA stenosis (>50%), 55 arteries (15%) are reclassified to another risk category. CONCLUSIONS: It is more reasonable to normalize maximal wall thickness to end-diastolic diameter rather than to IMT, affecting risk classification and suggesting modification of the Mannheim criteria. TRIAL REGISTRATION: Clinical trials.gov NCT01208025 .

Purpose Inhomogeneity of arterial wall thickness may be indicative of distal plaques. This study investigates the intra-subject association between relative spatial intima-media thickness (IMT) inhomogeneity of the common carotid artery (CCA) and the degree of stenosis of plaques in the internal carotid artery (ICA). Materials and Methods We included 240 patients with a recent ischemic stroke or transient ischemic attack and mild-to-moderate stenosis in the ipsilateral ICA. IMT inhomogeneity was extracted from B-mode ultrasound recordings. The degree of ICA stenosis was assessed on CT angiography according to the European Carotid Surgery Trial method. Patients were divided into groups with a low (≤ 2 %) and a high (> 2 %) IMT inhomogeneity scaled with respect to the local end-diastolic diameter. Results 182 patients had suitable CT and ultrasound measurements. Relative CCA-IMT inhomogeneity was similar for the symptomatic and asymptomatic side (difference: 0.02 %, p = 0.85). High relative IMT inhomogeneity was associated with a larger IMT (difference: 235 µm, p Conclusion Regardless of common risk factors, high relative CCA-IMT inhomogeneity is associated with a greater degree of ICA stenosis and is therefore indicative of atherosclerotic disease. The predictive value of CCA-IMT inhomogeneity for plaque progression and recurrence of cerebrovascular symptoms will be determined in the follow-up phase of PARISK.

Despite increased risk of neurological complications after cardiac surgery, monitoring of cerebral hemodynamics during cardiopulmonary bypass (CPB) is still not a common practice. Therefore, a technique to evaluate dynamic cerebral autoregulation and cerebral carbon dioxide reactivity (CO2R) during normothermic nonpulsatile CPB is presented. The technique uses continuous recording of invasive arterial blood pressure, middle cerebral artery blood flow velocity, absolute cerebral tissue oxygenation, in-line arterial carbon dioxide levels, and pump flow measurement in 37 adult male patients undergoing elective CPB. Cerebral autoregulation is estimated by transfer function analysis and the autoregulation index, based on the response to blood pressure variation induced by cyclic 6/min changes of indexed pump flow from 2.0 to 2.4 up to 2.8 L/min/m(2). CO2R was calculated from recordings of both cerebral blood flow velocity and cerebral tissue oxygenation. Cerebral autoregulation and CO2R were estimated at hypocapnia, normocapnia, and hypercapnia. CO2R was preserved during CPB, but significantly lower for hypocapnia compared with hypercapnia (p