Paul J Nederkoorn

National Human Genome Research Institute, 베서스다, Maryland, United States

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Publications (76)511.57 Total impact

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    ABSTRACT: Background and purpose: Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging. Methods: Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH. Results: IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12-6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH. Conclusions: In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.
    Stroke 10/2015; DOI:10.1161/STROKEAHA.115.008906 · 5.72 Impact Factor
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    ABSTRACT: Sickle cell disease (SCD) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Both local vaso-occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (CBF) have been proposed to be involved in the aetiology. We performed an explorative study to investigate the associations between WMHs and markers of endothelial dysfunction and CBF by quantifying WMH volume on 3·0 Tesla MRI. We included 40 children with HbSS or HbSβ(0) thalassaemia, with a mean age of 12·1 ± 2·6 years. Boys demonstrated an increased risk for WMHs (odds ratio 4·5, 95% confidence interval 1·2-17·4), unrelated to glucose-6-phosphate dehydrogenase deficiency. In patients with WMHs, lower fetal haemoglobin (HbF) was associated with a larger WMH volume (regression coefficient = -0·62, R(2) = 0·25, P = 0·04). Lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels were associated with lower CBF in the white matter (regression coefficient = 0·07, R(2) = 0·15, P = 0·03), suggesting that endothelial dysfunction could potentially hamper CBF. The findings of our explorative study suggest that a high level of HbF may be protective for WMHs and that endothelial dysfunction may contribute to the development of WMHs by reducing CBF.
    British Journal of Haematology 10/2015; DOI:10.1111/bjh.13819 · 4.71 Impact Factor
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  • Leo H. Bonati · Paul J. Nederkoorn ·

    Neuroimaging Clinics of North America 10/2015; DOI:10.1016/j.nic.2015.09.012 · 1.53 Impact Factor
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    Pediatric Rheumatology 09/2015; 13(Suppl 1):O7. DOI:10.1186/1546-0096-13-S1-O7 · 1.61 Impact Factor
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    ABSTRACT: Background: In patients with a space-occupying middle cerebral artery (MCA) infarct surgical decompression reduces the risk of death, but increases the chance of survival with severe disability. We assessed quality of life (QoL), symptoms of depression, and caregiver burden at long-term follow-up. Methods: Patients treated in two academic centres between 2007 and 2012 were included. Follow-up was at least six months. Patients and caregivers were interviewed separately. QoL was assessed with a visual analogue scale and the 36-item Short-Form health survey (SF-36); depression with the Hospital Anxiety and Depression Scale; and caregiver burden with the Caregiver Strain Index. Results: Twenty five patients were enrolled, of whom seven had an infarct in the dominant hemisphere. After a median follow-up of 26 months (IQR 11-46) the median SF-36 mental component score was 54.4 (IQR 45-60), indicating a mental QoL comparable to that in the general population. The median SF-36 physical component score was 32.7 (IQR 22-38), indicating a worse physical QoL. Dominance of the hemisphere did not influence QoL. 79 % of patients and 65 % of caregivers would, in retrospect, again choose for surgery. 26 % of patients had signs of depression and 64 % of caregivers were substantially burdened in their daily life. Conclusions: Mental QoL after surgical decompression for space-occupying MCA infarct is comparable to that in the general population, whereas physical QoL is worse. Dominance of the hemisphere did not influence QoL. The majority of caregivers experience substantial burden. Most patients and caregivers stand by their decision for hemicraniectomy.
    BMC Neurology 08/2015; 15(1):156. DOI:10.1186/s12883-015-0407-0 · 2.04 Impact Factor
  • Diederik van de Beek · Matthijs Brouwer · Paul Nederkoorn ·

    The Lancet 08/2015; 386(9994):653-4. DOI:10.1016/S0140-6736(15)61502-1 · 45.22 Impact Factor
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    ABSTRACT: -We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in ischemic stroke patients on novel oral anticoagulants (NOAC, last intake <48hours) compared to patients (i) taking vitamin K-antagonists (VKA) or (ii) without prior anticoagulation (no-OAC). -Multicenter cohort pilot study. Primary outcome measures were (i) occurrence of ICH in three categories - any intracranial hemorrhage (ICHany), symptomatic ICH according to the criteria of the ECASS-II (sICHECASS-II) and the NINDS thrombolysis trial (sICHNINDS); and (ii) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA-patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range [IQR] 8-22h). In VKA-patients, median pre-IVT/IAT INR was 1.3 (IQR 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9 % NOAC patients, compared to 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients compared to 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistical significant differences. -IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both, IVT/IAT in patients on subtherapeutic VKA-treatment or in those without prior anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.
    Circulation 07/2015; DOI:10.1161/CIRCULATIONAHA.115.015484 · 14.43 Impact Factor
  • Anne L Abbott · Paul J Nederkoorn ·

    Neurology 06/2015; 85(4). DOI:10.1212/WNL.0000000000001793 · 8.29 Impact Factor
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    ABSTRACT: There have been no ischemic stroke costing studies since major improvements were implemented in stroke care. We therefore determined hospital resource use and costs of ischemic stroke and TIA in the Netherlands for 2012. We conducted a retrospective cost analysis using individual patient data from a national diagnosis-related group registry. We analyzed 4 subgroups: inpatient ischemic stroke, inpatient TIA, outpatient ischemic stroke, and outpatient TIA. Costs of carotid endarterectomy and costs of an extra follow-up visit were also estimated. Unit costs were based on reference prices from the Dutch Healthcare Insurance Board and tariffs provided by the Dutch Healthcare Authority. Linear regression analysis was used to examine the association between hospital costs and various patient and hospital characteristics. A total of 35,903 ischemic stroke and 21,653 TIA patients were included. Inpatient costs were €5,328 ($6,845) for ischemic stroke and €2,470 ($3,173) for TIA. Outpatient costs were €495 ($636) for ischemic stroke and €587 ($754) for TIA. Costs of carotid endarterectomy were €6,836 ($8,783). Costs of inpatient days were the largest contributor to hospital costs. Age, hospital type, and region were strongly associated with hospital costs. Hospital costs are higher for inpatients and ischemic strokes compared with outpatients and TIAs, with length of stay (LOS) the most important contributor. LOS and hospital costs have substantially declined over the last 10 years, possibly due to improved hospital stroke care and efficient integrated stroke services. © 2015 American Academy of Neurology.
    Neurology 05/2015; 84(22). DOI:10.1212/WNL.0000000000001635 · 8.29 Impact Factor
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    ABSTRACT: Patients with a recent vertebrobasilar transient ischaemic attack or ischaemic stroke and vertebral artery stenosis of at least 50% have a high risk of future vertebrobasilar stroke. Stenting of vertebral artery stenosis is promising, but of uncertain benefit. We investigated the safety and feasibility of stenting of symptomatic vertebral artery stenosis of at least 50%, and assessed the rate of vascular events in the vertebrobasilar supply territory to inform the design of a phase 3 trial. Between Jan 22, 2008, and April 8, 2013, patients with a recent transient ischaemic attack or minor stroke associated with an intracranial or extracranial vertebral artery stenosis of at least 50% were enrolled from seven hospitals in the Netherlands in a phase 2 open-label trial with masked assessment of outcome. Patients were randomly allocated in a 1:1 ratio to stenting plus best medical treatment or best medical treatment alone by the local investigators using a web-based randomisation system. The primary outcome was the composite of vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment. The secondary outcomes were stroke in the supply territory of the symptomatic vertebral artery during follow-up, the composite outcome during follow-up, and the degree of stenosis in the symptomatic vertebral artery at 12 months. The trial is registered, number ISRCTN29597900. The trial was stopped after inclusion of 115 patients because of new regulatory requirements, including the use of a few prespecified stent types and external monitoring, for which no funding was available. 57 patients were assigned to stenting and 58 to medical treatment alone. Three patients in the stenting group had vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment (5%, 95% CI 0-11) versus one patient in the medical treatment group (2%, 0-5). During a median follow-up of 3 years (IQR 1·3-4·1), seven (12%, 95% CI 6-24) patients in the stenting group and four (7%, 2-17) in the medical treatment group had a stroke in the territory of the symptomatic vertebral artery; 11 (19%) patients in the stenting group and ten (17%) in the medical treatment group had vascular death, myocardial infarction, or any stroke. The small size of the vertebral artery and stent artifacts did not allow exact grading of restenosis on CT angiography. During the complete period of follow-up, there were 60 serious adverse events (eight strokes) in the stenting group and 56 (seven strokes) in the medical treatment alone group. Stenting of symptomatic vertebral artery stenosis is associated with a major periprocedural vascular complication in about one in 20 patients. In the population we studied, the risk of recurrent vertebrobasilar stroke under best medical treatment alone was low, questioning the need for and feasibility of a phase 3 trial. Dutch Heart Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Neurology 04/2015; 14(6). DOI:10.1016/S1474-4422(15)00017-4 · 21.90 Impact Factor

  • Neurology 04/2015; 84(20). DOI:10.1212/WNL.0000000000001581 · 8.29 Impact Factor
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    ABSTRACT: We investigated whether an active blood pressure-lowering strategy is associated with more patients receiving thrombolytics compared with a conservative "watch and measure" strategy, and assessed safety and functional outcome of these 2 treatment strategies. This is a post hoc analysis in 2 randomized controlled stroke trials, the PRACTISE (Promoting Acute Thrombolysis in Ischemic Stroke) and the PASS (Preventive Antibiotics in Stroke Study). We included all patients with elevated pretreatment blood pressure above 185/110 mm Hg at presentation but otherwise eligible for IV thrombolysis (IVT). The decision to use an active or conservative strategy was in accordance with local hospital treatment guidelines. The primary outcome was the proportion of patients treated with IVT. Secondary outcomes were (1) symptomatic intracranial hemorrhage (increased neurologic deficit with a concomitant hemorrhage on neuroimaging), (2) functional outcome at 3 months, and (3) the door-to-needle time. We included 224 patients, 66 (29%) received the active and 158 (71%) the conservative strategy. In the active group, 55 patients (83%) received thrombolytics vs 87 (55%) in the conservative group, an increase of 28% (95% confidence interval: 16%-40%). If only patients actually treated with IVT were considered, the rate of symptomatic intracranial hemorrhage was 7% in both groups. There was no difference in door-to-needle time. Active blood pressure lowering was associated with an increased proportion of patients treated with IVT compared with a conservative strategy, without a difference in symptomatic hemorrhage rate. © 2015 American Academy of Neurology.
    Neurology 03/2015; 84(14). DOI:10.1212/WNL.0000000000001445 · 8.29 Impact Factor
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    ABSTRACT: Patients with sickle cell anemia (SCA) are at a high risk to develop cerebral damage. Most common are silent cerebral infarctions (SCIs), visible as white matter hyperintensities (WMHs) on MRI in a patient without neurological deficits. The etiology of SCIs remains largely unclear. In addition, patients are at an increased risk for overt stroke, which is associated with large vessel disease. This classification based on the presence or absence of neurological deficits may not be the most fitting for research purposes, as it does not match the different underlying pathology. A classification based on imaging findings may therefore be a more straightforward approach for research purposes. We explored the feasibility to identify imaging features of SCIs in young, asymptomatic patients with SCA using ultra high-field 7 Tesla (7T) MRI. 7T MRI has a high resolution, which offers a unique chance to investigate small subclinical brain lesions in detail. To explore the superiority of 7T in identifying imaging abnormalities, we compared our results with 3T MRI. Ten young, neurologically asymptomatic patients with SCA underwent 7T and 3T MRI; 10 healthy, age-matched controls underwent 7T MRI. We used existing neuroimaging standards to classify the brain lesions. We scored 7T and 3T scans separately, blinded for all other results. Using 7T MRI, we identified more patients with intracerebral lesions (9/10 vs. 5/10), a higher total count of WMHs (203 vs. 190, p = 0.016) and more lacunes (5 vs. 4) compared to 3T MRI. Abnormalities seen on 7T, which could not be identified on 3T, were cortical hyperintensities (in 3/10) and a different aspect of irregular WMHs, closely associated with cortical hyperintensities in a patient with large vessel stenosis. In 7 controls, a total of 13 WMHs were present. Using 7T MRI, we identified more intracerebral lesions compared to 3T, and found several abnormalities not visible on 3T. 7T MRI in SCA seems of particular interest to study the cortical involvement and the relation between WMHs and the cortex. We found some imaging features that are thought to be representative for small vessel disease, including WMHs, lacunes and prominent perivascular spaces; to understand whether small vessel disease plays a role in SCA requires further research. © 2015 S. Karger AG, Basel.
    Cerebrovascular Diseases 03/2015; 39(3-4):181-189. DOI:10.1159/000373917 · 3.75 Impact Factor
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    ABSTRACT: Brain lesions on diffusion-weighted imaging (DWI) are frequently found after carotid artery stenting (CAS), but their clinical relevance remains unclear. This study sought to investigate whether periprocedural ischemic DWI lesions after CAS or carotid endarterectomy (CEA) are associated with an increased risk of recurrent cerebrovascular events. In the magnetic resonance imaging (MRI) substudy of ICSS (International Carotid Stenting Study), 231 patients with symptomatic carotid stenosis were randomized to undergo CAS (n = 124) or CEA (n = 107). MRIs were performed 1 to 7 days before and 1 to 3 days after treatment. The primary outcome event was stroke or transient ischemic attack in any territory occurring between the post-treatment MRI and the end of follow-up. Time to occurrence of the primary outcome event was compared between patients with (DWI+) and without (DWI-) new DWI lesions on the post-treatment scan in the CAS and CEA groups separately. Median time of follow-up was 4.1 years (interquartile range: 3.0 to 5.2). In the CAS group, recurrent stroke or transient ischemic attack occurred more often among DWI+ patients (12 of 62) than among DWI- patients (6 of 62), with a cumulative 5-year incidence of 22.8% (standard error [SE]: 7.1%) and 8.8% (SE: 3.8%), respectively (unadjusted hazard ratio: 2.85; 95% confidence interval: 1.05 to 7.72; p = 0.04). In DWI+ and DWI- patients, 8 and 2 events, respectively, occurred within 6 months after treatment. In the CEA group, there was no difference in recurrent cerebrovascular events between DWI+ and DWI- patients. Ischemic brain lesions discovered on DWI after CAS seem to be a marker of increased risk for recurrent cerebrovascular events. Patients with periprocedural DWI lesions might benefit from more aggressive and prolonged antiplatelet therapy after CAS. (A Randomised Comparison of the Risks, Benefits and Cost Effectiveness of Primary Carotid Stenting With Carotid Endarterectomy: International Carotid Stenting Study; ISRCTN25337470). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 02/2015; 65(6):521-529. DOI:10.1016/j.jacc.2014.11.038 · 16.50 Impact Factor
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    ABSTRACT: Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes. The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes. The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP. Trial registration Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.
    Trials 10/2014; 15(1):382. DOI:10.1186/1745-6215-15-382 · 1.73 Impact Factor
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    ABSTRACT: In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH.
    Stroke 09/2014; 45(11). DOI:10.1161/STROKEAHA.114.006800 · 5.72 Impact Factor
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    ABSTRACT: Background In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci.DesignThe String-of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients.AimsThe study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies.
    International Journal of Stroke 09/2014; 10(1). DOI:10.1111/ijs.12359 · 3.83 Impact Factor
  • Tessa van Middelaar · Paul J. Nederkoorn · H. Bart van der Worp · Jan Stam · Edo Richard ·
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    ABSTRACT: Background and PurposeIn patients with space-occupying middle cerebral artery infarction, surgical decompression strongly reduces risk of death and increases the chance of a favorable outcome. This comes at the expense of an increase in the risk of survival with (moderately) severe disability. We assessed quality of life, depression, and caregiver burden in these patients.Summary of ReviewWe systematically reviewed the literature by searching MEDLINE, EMBASE, and PsycINFO up to March 2014. We included randomized controlled trials, cohort studies, case–control studies, and case series with quality of life, depression, or caregiver burden as primary or secondary outcome. Seventeen articles reporting on 459 patients were included. At final follow-up at 7 to 51 months, 1344 patients (30%) had died, and 34 (11%) were lost to follow up. Data on 291 patients were available, of whom 81 of 213 survivors (39%) achieved good functional outcome at final follow-up (modified Rankin Scale ≤3). Mean quality of life was 46% to 67% of the best possible score when based on questionnaires or visual analogue scales. At final follow-up, 143 of 189 patients (76%) would in retrospect again choose for surgical decompression. Severe depressive symptoms were present in 14 of 113 patients (16%). Three studies investigated caregiver burden and reported substantial burden. Patients more than 60 years old had a lower quality of life in comparison with younger patients.Conclusions Most patients treated with surgical decompression for space-occupying infarction have a reasonable quality of life at long-term follow-up and are satisfied with the treatment received. Severe depressive symptoms are uncommon.
    International Journal of Stroke 08/2014; 10(2). DOI:10.1111/ijs.12329 · 3.83 Impact Factor
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    Paul J Nederkoorn · Diederik van de Beek ·

    International Journal of Stroke 07/2014; 9(5):E22. DOI:10.1111/ijs.12285 · 3.83 Impact Factor

Publication Stats

2k Citations
511.57 Total Impact Points


  • 2015
    • National Human Genome Research Institute
      베서스다, Maryland, United States
    • Monash University (Australia)
      Melbourne, Victoria, Australia
  • 2009-2015
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2008-2015
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Neurology
      Amsterdamo, North Holland, Netherlands
  • 2007-2015
    • Erasmus Universiteit Rotterdam
      • Department of Radiology
      Rotterdam, South Holland, Netherlands
  • 2002-2006
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 2005
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2003
    • Harvard University
      • Department of Health Policy and Management
      Cambridge, Massachusetts, United States
  • 2000-2003
    • University Medical Center Utrecht
      • Image Sciences Institute
      Utrecht, Utrecht, Netherlands