Floris H.B.M. Schreuder

Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA‐ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies.

Plaque at RISK (PARISK): Prospective Multicenter Study to Improve Diagnosis of High-Risk Carotid Plaques

Background Patients with symptomatic carotid artery stenosis are at high risk for recurrent stroke. To date, the decision to perform carotid endarterectomy in patients with a recent cerebrovascular event is mainly based on degree of stenosis of the ipsilateral carotid artery. However, additional atherosclerotic plaque characteristics might be better predictors of stroke, allowing for more precise selection of patients for carotid endarterectomy. Aims and hypothesis We investigate the hypothesis that the assessment of carotid plaque characteristics with magnetic resonance imaging, multidetector-row computed tomography angiography, ultrasonography, and transcranial Doppler, either alone or in combination, may improve identification of a subgroup of patients with <70% carotid artery stenosis with an increased risk of recurrent stroke. Methods The Plaque At RISK (PARISK) study is a prospective multicenter cohort study of patients with recent (<3 months) neurological symptoms due to ischemia in the territory of the carotid artery and < 70% ipsilateral carotid artery stenosis who are not scheduled for carotid endarterectomy or stenting. At baseline, 300 patients will undergo magnetic resonance imaging, multidetector-row computed tomography angiography, and ultrasonography examination of the carotid arteries. In addition, magnetic resonance imaging of the brain, ambulatory transcranial Doppler recording of the middle cerebral artery and blood withdrawal will be performed. After two-years, imaging will be repeated in 150 patients. All patients undergo a follow-up brain magnetic resonance imaging, and there will be regular clinical follow-up until the end of the study. Study outcomes The combined primary end-point contains ipsilateral recurrent ischemic stroke or transient ischemic attack or new ipsilateral ischemic brain lesions on follow-up brain magnetic resonance imaging.

Reproducibility of Fibrous Cap Status Assessment of Carotid Artery Plaques by Contrast-Enhanced MRI

Background and Purpose— Reproducibility in identifying the fibrous cap (FC) of carotid artery plaques by noncontrast-enhanced MRI has been shown to be poor. The objective of this study was to assess the reproducibility of multisequence MRI, including contrast-enhanced images, in assessing FC status. Methods— Forty-five symptomatic patients with 30% to 69% carotid artery stenosis underwent a multisequence MRI protocol, which included contrast-enhanced images. FC status (ie, discrimination between fibrotic and/or calcified plaques, plaques with a lipid-rich necrotic core and an intact and thick FC, and plaques with a lipid-rich necrotic core and a thin and/or ruptured FC) was independently assessed by 3 observers of which one also scored all images on a different occasion. Linear weighted kappa coefficients (&kgr;) were calculated as indicators of inter- and intraobserver agreement. Results— On a per-slice basis, interobserver agreement was good (&kgr;=0.60, 0.64, and 0.71), whereas intraobserver agreement was very good (&kgr;=0.86). On a per-plaque basis, interobserver agreement was good (&kgr;=0.64, 0.69, and 0.78), whereas intraobserver agreement was very good (&kgr;=0.96). Conclusion— This study found good interobserver and very good intraobserver agreement in assessing FC status of carotid artery plaques. Future studies are warranted to determine the predictive value of FC status assessment by multisequence MRI, including contrast-enhanced images, on the occurrence of (recurrent) cerebral ischemic events.

Wall Irregularity Rather Than Intima-Media Thickness is Associated with Nearby Atherosclerosis

In addition to intima-media thickness (IMT), IMT inhomogeneity may carry information about atherosclerosis progression. In 147 vascular diseased patients (mean 66 y, 48% male), we determined the carotid bulb stenosis degree based on local Doppler blood flow velocities. Common carotid artery (CCA) morphologic characteristics, i.e. IMT, IMT-inhomogeneity (intraregistration variation) and IMT uni- and bilateral intrasubject variation (DeltaIMT), were measured using multiple M-mode. Associations of morphologic characteristics, stenosis degree and Framingham score were evaluated with Pearson correlation (r) and multiple regression analysis. The IMT distributions for subjects without and with stenosis were not similar. The stenosis degree score correlated significantly to unilateral (r=0.68) and bilateral DeltaIMT (r=0.62), IMT (r=0.41) and IMT-inhomogeneity (r=0.45). The averaged IMT and IMT-inhomogeneity increased slightly for singular stenosis and abruptly for multiple stenoses. Mean uni- and bilateral DeltaIMT per stenosis degree increased linearly with this degree, reaching a correlation close to 1 (r=0.98 and r=0.97). Interestingly, the majority of the subjects with a moderate to severe bulb stenosis exhibited a carotid IMT lower than the considered critical threshold of 0.9 mm. In conclusion, although CCA is not prone to plaques, its morphologic characteristics are positively correlated with stenosis degree score and other risk scores. DeltaIMT can be more reliable derived from inter-registration rather than from intra-registration variation. In the CCA, DeltaIMT substantiates vascular alteration better than IMT.

Outcome of intracerebral hemorrhage associated with different oral anticoagulants

Objective: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH). Methods: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. Results: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]). Conclusions: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.

Measurement of common carotid artery intima-media thickness in clinical practice: comparison of B-mode and RF-based technique.

PURPOSE The common carotid artery intima-media thickness (CCA-IMT) is usually measured using B-mode ultrasound images. A different approach for CCA-IMT detection is based on radio frequency (RF) multiple M-line analysis. MATERIALS AND METHODS The present study explores the relationship between B-mode and RF measurement of CCA-IMT, as well as the reproducibility of both methods in 136 patients recently diagnosed with cardiovascular disease. Within one session, repeated measurements were made in the distal CCA bilaterally, using the B-mode (averaged over 10 mm) and RF technique (averaging 12 M-lines over 14 mm). RESULTS The two methods correlate well (Pearson r = 0.765). The CCA-IMT values measured with B-mode and RF were 0.779 +/- 0.196 mm and 0.734 +/- 0.172 mm, respectively. B-mode CCA-IMT is significantly larger than RF CCA-IMT (mean difference of 0.045 mm, SEM 7.8 microm; t = 5.82; p < 0.001). In the multivariate regression analysis, carotid artery stenosis, inhomogeneous IMT and diabetes mellitus were the main predictors of differences between B-mode and RF CCA-IMT. The intrapatient variation for B-mode and RF-based CCA-IMT is comparable (0.05 +/- 0.04 mm and 0.07 +/- 0.05 mm, respectively). CONCLUSION CCA-IMT values measured with RF and B-mode have similar reproducibility and exhibit acceptable correlation, but RF CCA-IMT is significantly smaller. The difference between both methods is mainly due to advanced atherosclerosis. Hence, both methods can be used reliably to measure CCA-IMT in clinical practice.

Incidence of Oral Anticoagulant–Associated Intracerebral Hemorrhage in the Netherlands

Background and Purpose— The aim of this study was to estimate the annual adult incidence and risk of intracerebral hemorrhage (ICH) and oral anticoagulant–associated ICH (OAC-ICH) in the Netherlands. Methods— We retrospectively selected all consecutive adult patients with a nontraumatic ICH seen in 1 of 3 hospitals in the region South-Limburg, the Netherlands, from 2007 to 2009. Crude incidences were age-adjusted to Dutch and European population. Results— We identified 652 ICH cases, of which 168 (25.8%) were OAC associated. The adult Dutch age-adjusted annual incidence of ICH and OAC-ICH was 34.8 (95% confidence interval, 32.0–37.8) and 8.7 (95% confidence interval, 7.3–10.3) per 100 000 person-years, respectively. The absolute risk of OAC-ICH was estimated at 0.46% per patient-year of OAC treatment. Conclusions— The annual incidences of ICH and OAC-ICH are relatively high in the Netherlands when compared with international literature.

Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 18F-Fluorocholine Positron Emission Tomography-Computed Tomography: Prospective Study on Vulnerable Atheroma With Immunohistochemical Validation

Background— 18F-fluorocholine (18F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that 18F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation. Methods and Results— Ten consecutive stroke patients (90% men, median age 66.5 years, range, 59.4–69.7) with ipsilateral >70% carotid artery stenosis and who underwent carotid endarterectomy were included in the study. Before carotid endarterectomy, all patients underwent positron emission tomography to assess maximum 18F-FCH uptake in ipsilateral symptomatic carotid plaques and contralateral asymptomatic carotid arteries, which was corrected for background activity, resulting in a maximum target-to-background ratio (TBRmax). Macrophage content was assessed in all carotid endarterectomy specimens as a percentage of CD68+-staining per whole plaque area (plaqueCD68+) and as a maximum CD68+ percentage (maxCD68+) in the most inflamed section/plaque. Dynamic positron emission tomography imaging demonstrated that an interval of 10 minutes between 18F-FCH injection and positron emission tomography acquisition is appropriate for carotid plaque imaging. TBRmax in ipsilateral symptomatic carotid plaques correlated significantly with plaqueCD68+ (Spearman’s ρ=0.648, P =0.043) and maxCD68+ (ρ=0.721, P =0.019) in the 10 corresponding carotid endarterectomy specimens. TBRmax was significantly higher ( P =0.047) in ipsilateral symptomatic carotid plaques (median: 2.0; interquartile range [Q1–Q3], 1.5–2.5) compared with the contralateral asymptomatic carotid arteries (median: 1.4; Q1–Q3, 1.3–1.6). TBRmax was not significantly correlated to carotid artery stenosis (ρ=0.506, P =0.135). Conclusions— In vivo uptake of 18F-FCH in human carotid atherosclerotic plaques correlated strongly with degree of macrophage infiltration and recent symptoms, thus 18F-FCH positron emission tomography is a promising tool for the evaluation of vulnerable plaques. Clinical Trial Registration— URL: . Unique identifier: [NCT01899014][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01899014&atom=%2Fcirccvim%2F9%2F5%2Fe004467.atomBackground—18F-fluorocholine (18F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that 18F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation. Methods and Results—Ten consecutive stroke patients (90% men, median age 66.5 years, range, 59.4–69.7) with ipsilateral >70% carotid artery stenosis and who underwent carotid endarterectomy were included in the study. Before carotid endarterectomy, all patients underwent positron emission tomography to assess maximum 18F-FCH uptake in ipsilateral symptomatic carotid plaques and contralateral asymptomatic carotid arteries, which was corrected for background activity, resulting in a maximum target-to-background ratio (TBRmax). Macrophage content was assessed in all carotid endarterectomy specimens as a percentage of CD68+-staining per whole plaque area (plaqueCD68+) and as a maximum CD68+ percentage (maxCD68+) in the most inflamed section/plaque. Dynamic positron emission tomography imaging demonstrated that an interval of 10 minutes between 18F-FCH injection and positron emission tomography acquisition is appropriate for carotid plaque imaging. TBRmax in ipsilateral symptomatic carotid plaques correlated significantly with plaqueCD68+ (Spearman’s &rgr;=0.648, P=0.043) and maxCD68+ (&rgr;=0.721, P=0.019) in the 10 corresponding carotid endarterectomy specimens. TBRmax was significantly higher (P=0.047) in ipsilateral symptomatic carotid plaques (median: 2.0; interquartile range [Q1–Q3], 1.5–2.5) compared with the contralateral asymptomatic carotid arteries (median: 1.4; Q1–Q3, 1.3–1.6). TBRmax was not significantly correlated to carotid artery stenosis (&rgr;=0.506, P=0.135). Conclusions—In vivo uptake of 18F-FCH in human carotid atherosclerotic plaques correlated strongly with degree of macrophage infiltration and recent symptoms, thus 18F-FCH positron emission tomography is a promising tool for the evaluation of vulnerable plaques. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01899014.

Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage

Objective: Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. Methods: An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. Results: Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB+ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). Conclusion: In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge.

Visualization of Local Changes in Vessel Wall Morphology and Plaque Progression in Serial Carotid Artery Magnetic Resonance Imaging

Carotid atherosclerosis is an important cause of ischemic stroke. Assessment of plaque composition in addition to degree of luminal stenosis can be used to identify patients with increased risk of stroke and assess disease progression. Magnetic resonance imaging (MRI) is an excellent noninvasive imaging technique to assess vessel wall morphology and plaque composition, with good accuracy and reproducibility.1 Serial MRI of the carotid artery is used in several studies which focus on measuring the natural history of carotid artery plaques in symptomatic1 and asymptomatic2 patients and effects of lipid-lowering therapy using statins.3,4 The current standard to analyze serial MRI scans is to compare volume measurements based on manual segmentations of the vessel wall and plaque components. Before comparing the scans, the scans have to be aligned to each other on a slice level. Different approaches exist to align scans from different time points. One study aligns the scans by centering the image stack at each time point over the plaque,1 and another study uses the baseline scan as a reference at the follow-up session to ensure targeting the same arterial segment.4 Alternatively, postprocessing can be used to match the axial images from different time points according to their distance to the carotid bifurcation.2,3 Furthermore, comparison between time points is hindered by inconsistent repositioning of the artery from scan to scan in conjunction with thick image slices. Balu et al5 studied the influence of subject repositioning on measurement precision in serial MRI and identified orientation variability as the most important factor that affected reproducibility. Besides repositioning variability, the current comparison of time points is primarily based on volume measurements, which is a limited representation of the available image data, and no attention is given to local changes or visual …