L J Kappelle

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (338)1231.35 Total impact

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    ABSTRACT: The purpose of this study was to assess whether calibrated magnetic resonance imaging (MRI) can identify regional variances in cerebral hemodynamics caused by vascular disease. For this, arterial spin labeling (ASL)/blood oxygen level-dependent (BOLD) MRI was performed in 11 patients (65±7 years) and 14 controls (66±4 years). Cerebral blood flow (CBF), ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were evaluated. The CBF was 34±5 and 36±11 mL/100 g per minute in the ipsilateral middle cerebral artery (MCA) territory of the patients and the controls. Arterial spin labeling CVR was 44±20 and 53±10% per 10 mm Hg ▵EtCO2 in patients and controls. The BOLD CVR was lower in the patients compared with the controls (1.3±0.8 versus 2.2±0.4% per 10 mm Hg ▵EtCO2, P<0.01). The OEF was 41±8% and 38±6%, and the CMRO2 was 116±39 and 111±40 μmol/100 g per minute in the patients and the controls. The BOLD CVR was lower in the ipsilateral than in the contralateral MCA territory of the patients (1.2±0.6 versus 1.6±0.5% per 10 mmHg ▵EtCO2, P<0.01). Analysis was hampered in three patients due to delayed arrival time. Thus, regional hemodynamic impairment was identified with calibrated MRI. Delayed arrival artifacts limited the interpretation of the images in some patients.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 February 2015; doi:10.1038/jcbfm.2015.14.
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    ABSTRACT: Aneurysms of the extracranial carotid artery (ECAA) are rare. Although most ECAA are identified in asymptomatic patients, serious neurological complications may occur. Current literature on treatment outcome contains mainly case reports and small case series with incomplete data and lack of long--term follow--up. There is clear lack on natural follow--up data, and there is no clear treatment algorithm. An international web--based registry to collect data on patients with ECAA is designed to provide clinical guidance on this scarce pathology. The Carotid Aneurysm Registry (CAR) is open for inclusion of all patients with a fusiform or saccular ECAA. Patients with primary or secondary ECAA can be enrolled in CAR independent of the type of treatment (conservative or invasive). CAR participation does not interfere with the local physician's treatment policy. Follow--up and imaging can also be scheduled according to local clinical practice. The primary endpoint of the CAR in conservative patients is occurrence of symptoms related to the aneurysm at 30 days, one, three, and five years. The primary endpoint in invasively treated patients is freedom from symptoms of the aneurysm at 30 days, one, three, and five years. Analyses will relate outcome to etiology, imaging characteristics, ECAA growth patterns, and (if applicable) revascularization technique applied. The aim of the registry is to prospectively collect follow--up data on patients with an ECAA, being either treated conservatively or by invasive aneurysm exclusion strategies. The CAR database will be used to address diagnostic and therapeutic research questions. Collecting and analyzing the data gained from the registry could be the first step towards development of treatment guidelines and expert consensus for the management of ECAA.
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    ABSTRACT: Background In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. Methods We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). Results We enrolled 500 patients at 16 medical centers in the Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. Conclusions In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.) The New England Journal of Medicine Downloaded from nejm.org on December 18, 2014. For personal use only. No other
    New England Journal of Medicine 12/2014; DOI:10.1056/NEJMoa1411587 · 54.42 Impact Factor
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    ABSTRACT: Low-grade inflammation and endothelial dysfunction are related to cognitive decline and dementia, in a complex interplay with vascular factors and aging. We investigated, in an older population, low-grade inflammation and endothelial dysfunction in relation to detailed assessment of cognitive functioning. Furthermore, we explored this association within the context of vascular factors. 377 participants (73 ± 6 years) of the population-based Hoorn Study were included. In plasma samples of 2000–2001 (n = 363) and/or 2005–2008 (n = 323), biomarkers were determined of low-grade inflammation (CRP, TNF-alpha, IL-6, IL-8, SAA, MPO, and sICAM-1) and endothelial dysfunction (vWF, sICAM-1, sVCAM-1, sTM, sE-selectin). In 2005–2008, all participants underwent neuropsychological examination. Composite z-scores were computed for low-grade inflammation and endothelial dysfunction at both time points, and for six domains of cognitive functioning (abstract reasoning, memory, information processing speed, attention and executive functioning, visuoconstruction, and language). The association between low-grade inflammation and endothelial dysfunction, and cognitive functioning was evaluated with linear regression analysis. In secondary analyses, we explored the relation with vascular risk factors and cardiovascular disease. Low-grade inflammation and endothelial dysfunction were associated with worse performance on information processing speed and attention and executive functioning, in prospective and cross-sectional analyses (standardized betas ranging from −0.20 to −0.10). No significant relation with other cognitive domains was observed. Adjusting for vascular factors slightly attenuated the associations. Low-grade inflammation and endothelial dysfunction accounted for only 2.6% explained variance in cognitive functioning, on top of related vascular risk factors and cardiovascular disease. Bootstrapping analyses show that low-grade inflammation and endothelial dysfunction mediate the relation between vascular risk factors and cognitive functioning. This study shows that low-grade inflammation and endothelial dysfunction contribute to reduced information processing speed and executive functioning in an older population.
    Psychoneuroendocrinology 02/2014; 40:108–118. DOI:10.1016/j.psyneuen.2013.11.011 · 5.59 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: We investigated predictors for acute and persisting periprocedural ischemic brain lesions among patients with symptomatic carotid stenosis randomized to stenting or endarterectomy in the International Carotid Stenting Study. METHODS: We assessed acute lesions on diffusion-weighted imaging 1 to 3 days after treatment in 124 stenting and 107 endarterectomy patients and lesions persisting on fluid-attenuated inversion recovery after 1 month in 86 and 75 patients, respectively. RESULTS: Stenting patients had more acute (relative risk, 8.8; 95% confidence interval, 4.4-17.5; P<0.001) and persisting lesions (relative risk, 4.2; 95% confidence interval, 1.6-11.1; P=0.005) than endarterectomy patients. Acute lesion count was associated with age (by trend), male sex, and stroke as the qualifying event in stenting; high systolic blood pressure in endarterectomy; and white matter disease in both groups. The rate of conversion from acute to persisting lesions was lower in the stenting group (relative risk, 0.4; 95% confidence interval, 0.2-0.8; P=0.007), and was only predicted by acute lesion volume. CONCLUSIONS: Stenting caused more acute and persisting ischemic brain lesions than endarterectomy. However, the rate of conversion from acute to persisting lesions was lower in the stenting group, most likely attributable to lower acute lesion volumes. Clinical Trial Registration -URL: www.isrctn.org. Unique identifier: ISRCTN25337470.
    Stroke 02/2014; 45(2-2):591-4. DOI:10.1161/STROKEAHA.113.003605 · 6.02 Impact Factor
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    ABSTRACT: In patients with recently symptomatic carotid artery stenosis, guidelines recommend carotid revascularization within 2 weeks of the index event. The "index event" may be defined as either the first or the most recent event. The delay between the index event and carotid endarterectomy (CEA) over a period of 6 years in a single centre was evaluated and the effect of defining the index event as either the first or the most recent event was assessed. Observational study. 555 consecutive patients with symptomatic carotid stenosis ≥50% treated with CEA between 2007 and 2012 were assessed. In 2010, changes to the in-hospital process of care to reduce delays in referral and CEA were introduced. These changes included, for example, improving access to physicians, imaging, and operating rooms. The delay from symptoms to surgery was expressed in days. The median time between the first event and surgery was reduced from 53 days (interquartile range [IQR] 30-78) in 2007 to 21 days (IQR 12-45) in 2012, and between the most recent event and CEA from 45 days (IQR 28-67) to 17 days (IQR 9-28). Patients referred directly by their general practitioner more often underwent CEA within 2 weeks than patients referred by specialists from other hospitals. Compared to patients with transient ischaemic attack or ocular symptoms, patients with ischaemic stroke more often underwent CEA within 2 weeks. A small change in the process of care significantly reduced the delay from the index event to CEA, but in 2012 it still exceeded 14 days in the majority of patients. The definition of the "index event" has a large impact on the total duration of delay, and should therefore be uniform across studies.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 01/2014; DOI:10.1016/j.ejvs.2013.12.013 · 2.92 Impact Factor
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    ABSTRACT: Background: In stroke erythrocyte-rich thrombi are more sensitive to intravenous thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have higher density on non-contrast CT (NCCT). We investigated the relationship between thrombus density and recanalization and whether persistent occlusions can be predicted by Hounsfield unit (HU) measurements. Methods: In 88 IV-rtPA-treated patients with intracranial ICA or MCA occluding thrombus and follow-up imaging, thrombus and contralateral vessel attenuation measurements were performed on thin-slice NCCT. Mean absolute and relative HU were compared between patients with persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade 0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted for stroke subtype, clot burden score, occlusion site and time to thrombolysis) odds ratios for persistent occlusion were calculated. Additional prognostic value for persistent occlusion was estimated by adding HU measurements to the area under the curve (AUC) of known determinants and calculating optimal cut-off values. Results: Patients with persistent occlusion (n = 19) had significant lower mean HU (absolute 52.2 ± 9.5, relative 1.29 ± 0.20) compared to recanalization (absolute 63.1 ± 10.7, relative 1.54 ± 0.23, both p < 0.0001). Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6-6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per 0.20 relative HU decrease. Attenuation measurements significantly increased the AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative HU). Cut-off values of <56.5 absolute HU and <1.38 relative HU showed optimal predictive values for persistent occlusion. Conclusions: Thrombus density is related to recanalization rate. Lower absolute and relative HU are independently related to persistent occlusion and HU measurements significantly increase discriminative performances of known recanalization determinants. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 01/2014; 37(2):116-122. DOI:10.1159/000357420 · 3.70 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    International Journal of Stroke 10/2013; DOI:10.1111/ijs.12167 · 4.03 Impact Factor
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    ABSTRACT: The occurrence of cerebral ischemia during carotid endarterectomy (CEA) can be prevented by (selective) placement of an intraluminal shunt during cross-clamping. We set out to develop a rule to predict the likelihood for shunting during CEA based on preoperative assessment of collateral cerebral circulation and patient characteristics. Patients who underwent CEA between 2004 and 2010 were included. Patients without preoperative magnetic resonance (MRA) or computed tomography angiography (CTA) were excluded. The primary endpoint was intraluminal shunt placement based on electroencephalography changes. Age, sex, cardiovascular risk factors peripheral artery disease, symptomatic status, degree of ipsilateral and contralateral carotid, status of the vertebral arteries, and morphology of the CoW were studied as potential predictors for shunt use. A prediction model was derived from a multivariable regression model using discrimination, calibration, and bootstrapping approaches and transformed into a clinical prediction model. A total of 431 patients were included, of which 65 patients (15%) received an intraluminal shunt. In the MRA group (n = 285) factors related to shunt use in multivariate analysis were ipsilateral carotid stenosis 90-99% (odds ratio [OR] 0.15, 95% CI 0.04-0.53), contralateral carotid occlusion (OR 4.29, 95% CI 1.68-10.95) and any not-visible anterior (OR 4.96, 95% CI 1.95-12.58) or ipsilateral posterior segment of the CoW (OR 5.08, 95% CI 2.10-12.32). In the CT group none of the factors were independently related to shunt use; therefore, only predictors describing morphology of CoW derived from MRA findings were included in our model. The c-statistic of this model was 0.79 (95% CI 0.72-0.86). Among patients with an estimated chance of needing a shunt of under 10% (49% of the population), the likelihood of shunting was 5%. In those in whom this chance was estimated higher than 30% (13% of the population) the likelihood was 51%. Among patients scheduled for CEA, assessment of cerebral arteries and of the configuration of the CoW based on MRA-derived images can help to identify patients with low and high likelihood of the need of shunt use during surgery.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 09/2013; 46(6). DOI:10.1016/j.ejvs.2013.09.007 · 2.92 Impact Factor
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    ABSTRACT: This study assessed the value of cerebral near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) in relation to electroencephalography (EEG) changes for the detection of cerebral hypoperfusion necessitating shunt placement during carotid endarterectomy (CEA). This was a prospective cohort study. Patients with a sufficient TCD window undergoing CEA from February 2009 to June 2011 were included. All patients were continuously monitored with NIRS and EEG. An intraluminal shunt was placed, selectively determined by predefined EEG changes in alpha, beta, theta, or delta activity. Relative changes in regional cerebral oxygen saturation (rSO2) in the frontal lobe and mean blood flow velocity (Vmean) 30 seconds before carotid cross-clamping versus 2 minutes after carotid cross-clamping were related to shunt placement. Receiver operating characteristic curve analysis was performed to determine the optimal thresholds. Diagnostic values were reported as positive and negative predictive value (PPV and NPV). Of a cohort of 151 patients, 17(11%) showed EEG changes requiring shunt placement. The rSO2 and Vmean decreased more in the shunt group than in the non-shunt group (mean ± standard error of the mean) 21 ± 4% versus 7 ± 5% and 76 ± 6% versus 12 ± 3%, respectively (p < .005), Receiver operating characteristic curve analysis revealed a threshold of 16% decrease in rSO2 (PPV 76% and NPV 99%) and 48% decrease in Vmean (PPV 53% and NPV 99%) as the optimal cut-off value to detect cerebral ischemia during CEA under general anesthesia. Compared with EEG, we found moderate PPV but high NPV for NIRS and TCD to detect cerebral ischemia during CEA under general anesthesia, meaning that both techniques independently may be suitable to exclude patients for unnecessary shunt use and to direct the use of selective shunting. However, the optimal thresholds for NIRS remain to be determined.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 08/2013; 46(4). DOI:10.1016/j.ejvs.2013.07.007 · 2.92 Impact Factor
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    ABSTRACT: To study the association between the epsilon 4 allele of apolipoprotein E (APOEε4) and delirium in a stroke population. 527 consecutive stroke patients were screened for delirium during the first week of admission with the confusion assessment method. In three hundred fifty-three patients genomic DNA isolation was available. The incidence of delirium after stroke in the 353 patients was 11.3%. There was no association between APOEε4 and delirium. Even after adjustment for IQCODE, stroke localization, stroke subtype, stroke severity, infection, and brain atrophy no association was found (odds ratio: 0.9; 95% confidence interval: 0.4-2.1). Delirium did not last longer in patients with an APOEε4 allele compared to patients without an APOEε4 allele (median: 5.6 days [range: 1-21] versus median: 4.6 days [range: 1-15], p = 0.5). There was no association between the presence of an APOEε4 allele and the occurrence of delirium in the acute phase after stroke.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 08/2013; 21(10). DOI:10.1016/j.jagp.2013.01.068 · 3.35 Impact Factor
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    ABSTRACT: Introduction More insights in the etiopathogenesis of thrombi could be helpful in the treatment of patients with acute ischemic stroke. The aim of our study was to determine the relationship between presence of a hyperdense vessel sign and thrombus density with different stroke subtypes. Methods We included 123 patients with acute ischemic anterior circulation stroke and a visible occlusion on CT-angiography caused by cardioembolism (n = 53), large artery atherosclerosis (n = 55), or dissection (n = 15). Presence or absence of a hyperdense vessel sign was assessed and thrombus density was measured in Hounsfield Units (HU) on non-contrast 1 mm thin slices CT. Subsequently, occurrence of hyperdense vessel sign and thrombus density (absolute HU and rHU (=HU thrombus/HU contralateral)) were related with stroke subtypes. Results The presence of hyperdense vessel signs differed significantly among subtypes and was found in 45, 64 and 93 % of patients with cardioembolism, large artery atherosclerosis and dissection, respectively (p = 0.003). The mean HU and rHU (+95 % CI) of the thrombi in all vessels were respectively 56.1 (53.2–59.0) and 1.39 (1.33–1.45) in cardioembolism, 64.6 (62.2–66.9) and 1.59 (1.54–1.64) in large artery atherosclerosis and 76.4 (73.0–79.8) and 1.88 (1.79–1.97) in dissection (p < 0.0001). We found the same significant ranking order in the density of thrombi with hyperdense vessel signs (mean HU and rHU (+95 % CI), respectively): cardioembolism 61.3 (57.4–65.3) and 1.49 (57.4–65.3); large artery atherosclerosis 67.3 (64.9–69.7) and 1.65 (1.58–1.71); dissection 76.4 (72.6–80.1) and 1.89 (1.79–1.99, p < 0.0001). Conclusion Presence of a hyperdense vessel sign and thrombus density are related to stroke subtype.
    Neuroradiology 06/2013; DOI:10.1007/s00234-013-1217-y · 2.37 Impact Factor
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    ABSTRACT: BACKGROUND: We developed and validated a risk score to predict delirium after stroke which was derived from our prospective cohort study where several risk factors were identified. METHODS: Using the β coefficients from the logistic regression model, we allocated a score to values of the risk factors. In the first model, stroke severity, stroke subtype, infection, stroke localisation, pre-existent cognitive decline and age were included. The second model included age, stroke severity, stroke subtype and infection. A third model only included age and stroke severity. The risk score was validated in an independent dataset. RESULTS: The area under the curve (AUC) of the first model was 0.85 (sensitivity 86%, specificity 74%). In the second model, the AUC was 0.84 (sensitivity 80%, specificity 75%). The third model had an AUC of 0.80 (sensitivity 79%, specificity 73%). In the validation set, model 1 had an AUC of 0.83 (sensitivity 78%, specificity 77%). The second had an AUC of 0.83 (sensitivity 76%, specificity 81%). The third model gave an AUC of 0.82 (sensitivity of 73%, specificity 75%). We conclude that model 2 is easy to use in clinical practice and slightly better than model 3 and, therefore, was used to create risk tables to use as a tool in clinical practice. CONCLUSIONS: A model including age, stroke severity, stroke subtype and infection can be used to identify patients who have a high risk to develop delirium in the early phase of stroke.
    Journal of neurology, neurosurgery, and psychiatry 06/2013; DOI:10.1136/jnnp-2013-304920 · 4.87 Impact Factor
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    ABSTRACT: The plasma concentration of adiponectin, an adipokine that has anti-inflammatory, anti-atherogenic and insulin sensitizing properties, is lower in obese subjects and could therefore be a target for therapy. In order to review and meta-analyse prospective cohort studies investigating adiponectin concentration and the risk for incident coronary heart disease (CHD) or stroke, a systematic search of MEDLINE, EMBASE and Cochrane databases was performed. Two independent reviewers selected prospective cohort studies investigating the relationship between adiponectin level and incident CHD or stroke using 'adiponectin' and 'cardiovascular disease' or 'stroke' and their synonyms, excluding patients with clinically manifest vascular disease. Random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). Generalized least squares regression was used to assess dose-response relationships for adiponectin concentrations from studies that provided RRs solely based upon categorical data regression. In total, 16 prospective cohort studies, comprising 23,919 patients and 6,870 CHD or stroke outcome events, were included in the meta-analyses. An increase of 1 standard deviation in log-transformed adiponectin did not lower the risk for CHD (RR 0.97; 95% CI 0.86-1.09). A 10 μg mL(-1) increase in adiponectin conferred a RR of 0.91 (95% CI 0.80-1.03) for CHD and a RR 1.01 (95% CI 0.97-1.06) for stroke. In conclusion, plasma adiponectin is not related to the risk for incident CHD or stroke.
    Obesity Reviews 03/2013; DOI:10.1111/obr.12027 · 7.86 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. METHODS: We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8-11.0 mmol/l) were randomized to metformin, in a daily dose of 2 g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762. RESULTS: Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3-10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97 mmol/l (95% CI 0·11-1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71 mmol/l; 95% CI -0·36 to 1·78). CONCLUSIONS: Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.
    International Journal of Stroke 03/2013; 10(1). DOI:10.1111/ijs.12023 · 4.03 Impact Factor
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    ABSTRACT: - One of the most devastating cognitive deficits following a stroke is when the patient neglects one half of the body and surroundings (unilateral neglect).- Unilateral neglect following a stroke has a high prevalence and is one of the most important predictors of poor functional outcome.- Various treatment methods have been studied over the past decades but their effects appear too short-term or task-specific and therefore, difficult to extrapolate to other untrained situations.- A possible new intervention is transcranial direct current stimulation (tDCS), which is capable of modulating brain activity by polarizing neurons with the aid of a constant low current.- Recent research suggests that inhibiting the intact hemisphere or increasing the neuronal activity in the damaged hemisphere might reduce unilateral neglect.- For treating unilateral neglect, tDCS appears to be a promising technique; however, more research is necessary to reveal its therapeutic potential.
    Nederlands tijdschrift voor geneeskunde 01/2013; 157(27):A6056.
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    ABSTRACT: Background: Small- and large-vessel disease (SVD and LVD, respectively) might have a different pathogenesis and prognosis but the long-term risk of death and recurrent stroke appears to be similar in previous studies. In this study, we investigated the long-term vascular prognosis of patients with LVD and SVD in a large cohort of well-documented patients. Methods: We included 971 patients with transient ischemic attack (TIA) or nondisabling ischemic stroke of atherosclerotic origin referred to a university hospital in the Netherlands between 1994 and 2005 and followed them for the occurrence of vascular events or death. The primary outcome was a composite of stroke, myocardial infarction and vascular death, whichever happened first. Classification of SVD/LVD was primarily based on brain imaging. We used regression analyses to generate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses were performed in subsets of the population, i.e. patients with subtype classification based on imaging, excluding TIA patients, first-ever stroke patients and LVD patients without a symptomatic carotid stenosis. Results: During a mean follow-up of 6.3 years, new vascular events occurred in 56 of 312 SVD patients (3.3%/year) and in 128 of 659 LVD patients (2.9%/year). These were ischemic strokes in 33 of the 56 events in SVD patients (2.0%/year) and 54 of the 128 events in LVD patients (1.2%/year). The corresponding age- and sex-adjusted HR for all new vascular events for LVD versus SVD was 0.76 (95% CI 0.56-1.05) for the total follow-up period. When this risk was split into early risk (<1 year) and late risk (>1 year), it was not significantly different for the 1-year risk of vascular events (HR 1.04, 95% CI 0.57-1.91); however, after 1 year of follow-up, LVD patients had fewer outcome events compared with SVD patients (HR 0.66, 95% CI 0.46-0.96). For ischemic strokes, the overall HR was 0.60 (95% CI 0.39-0.94). As with the primary outcome, here also the 1-year risk was not significantly different from >1-year risk (HR 1.31, 95% CI 0.62-2.81, and HR 0.36, 95% CI 0.21-0.63, respectively). The sensitivity analyses showed virtually the same results. Conclusion: In patients with nondisabling cerebrovascular disease, we found, despite no differences at baseline in terms of vascular risk factors, a better long-term prognosis for patients with LVD for all vascular events, especially for recurrent strokes. Our observations support a different pathogenesis in SVD and LVD patients, and optimal prevention is indicated for patients with what was formerly regarded as 'benign' SVD stroke.
    Cerebrovascular Diseases 01/2013; 36(3):190-5. DOI:10.1159/000353675 · 3.70 Impact Factor
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    ABSTRACT: Background: Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) is a potential life-threatening complication. Therefore, early identification and treatment of patients at risk is essential. CHS can be predicted by a doubling of postoperative transcranial Doppler (TCD)-derived mean middle cerebral artery blood velocity (V(mean)) compared to preoperative values. However, in approximately 15% of CEA patients, an adequate TCD signal cannot be obtained due to an insufficient temporal bone window. Moreover, the use of TCD requires specifically skilled personnel. An alternative and promising technique of noninvasive cerebral monitoring is relative frontal lobe oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS), which offers on-line information about cerebral oxygenation without the need for specialized personnel. In this study, we assess whether NIRS and perioperative TCD are related to the onset CHS following CEA. Methods: Patients who underwent CEA under general anesthesia and had a sufficient TCD window were prospectively included. The V(mean) and rSO(2) measured before induction of anesthesia were compared to measurements performed in the first postoperative hour (ΔV(mean), ΔrSO(2), respectively). Logistic regression analysis was performed to determine the relationship between ΔV and ΔrSO(2) and the occurrence of CHS. Subsequently, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values. Diagnostic values were shown as positive and negative predictive values (PPV and NPV). Results: In total, 151 patients were included, of which 7 patients developed CHS. The ΔV(mean) and ΔrSO(2) differed between CHS and non-CHS patients (median, interquartile range), i.e. 74% (67-103) versus 16% (-2 to 41), p = 0.001, and 7% (4-15) versus 1% (-6 to 7), p = 0.009, respectively. The mean arterial blood pressure did not change. Postoperative ΔV(mean) and ΔrSO(2) were significantly related to the occurrence of CHS [odds ratio (OR) 1.40 (95% CI 1.02-1.93) per 30% increase in V(mean) and OR 1.82 (95% CI 1.11-2.99) per 5% increase in rSO(2)]. ROC curve analysis showed an area under the curve of 0.88 (p = 0.001) for ΔV(mean) and an optimal cutoff value of 67% increase (PPV 38% and NPV 99%), and an area under the curve of 0.79 (p = 0.009) for ΔrSO(2) and an optimal cutoff value of 3% rSO(2) increase (PPV 11% and NPV 100%). The combination of both monitoring techniques provided a PPV of 58% and an NPV of 99%. Conclusions: Both TCD and NIRS measurements can be used to safely identify patients not at risk of developing CHS. It appears that NIRS is a good alternative when a TCD signal cannot be obtained.
    Cerebrovascular Diseases 11/2012; 34(4):314-321. DOI:10.1159/000343229 · 3.70 Impact Factor
  • Journal of Vascular Surgery 06/2012; 55(6):39S. DOI:10.1016/j.jvs.2012.03.114 · 2.98 Impact Factor
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    ABSTRACT: To develop a simple prognostic model to predict outcome at 1 month after acute basilar artery occlusion (BAO) with readily available predictors. The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational, international registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO. We considered predictors available at hospital admission in multivariable logistic regression models to predict poor outcome (modified Rankin Scale [mRS] score 4-5 or death) at 1 month. We used receiver operator characteristic curves to assess the discriminatory performance of the models. Of the 619 patients, 429 (69%) had a poor outcome at 1 month: 74 (12%) had a mRS score of 4, 115 (19%) had a mRS score of 5, and 240 (39%) had died. The main predictors of poor outcome were older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIH Stroke Scale (NIHSS) score, and longer time to treatment. A prognostic model that combined demographic data and stroke risk factors had an area under the receiver operating characteristic curve (AUC) of 0.64. This performance improved by including findings from the neurologic examination (AUC 0.79) and CT imaging (AUC 0.80). A risk chart showed predictions of poor outcome at 1 month varying from 25 to 96%. Poor outcome after BAO can be reliably predicted by a simple model that includes older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIHSS score, and longer time to treatment.
    Neurology 03/2012; 78(14):1058-63. DOI:10.1212/WNL.0b013e31824e8f40 · 8.30 Impact Factor

Publication Stats

9k Citations
1,231.35 Total Impact Points

Institutions

  • 1986–2015
    • University Medical Center Utrecht
      • • Department of Neurology
      • • Department of Hematology
      • • Department of Neurosurgery
      Utrecht, Utrecht, Netherlands
  • 2011–2013
    • St. Elisabeth Ziekenhuis Tilburg
      Tilburg, North Brabant, Netherlands
  • 1991–2013
    • Universiteit Utrecht
      • • Division of Experimental Psychology
      • • Department of Neurology
      Utrecht, Utrecht, Netherlands
  • 2009
    • Baylor College of Medicine
      • Department of Neurology
      Houston, Texas, United States
  • 2004
    • Technische Universiteit Eindhoven
      Eindhoven, North Brabant, Netherlands
  • 2003
    • Erasmus MC
      • Department of Neurology
      Rotterdam, South Holland, Netherlands
  • 2002
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 1989–2001
    • Erasmus Universiteit Rotterdam
      • • Department of Neurology
      • • Department of Medical Psychology and Psychotherapy
      Rotterdam, South Holland, Netherlands
  • 1999
    • The University of Western Ontario
      London, Ontario, Canada
  • 1998
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
  • 1992
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Neurology
      Amsterdam, North Holland, Netherlands