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Paul J Nederkoorn - Top 30 Publications

Response by Spaander et al to Letter Regarding Article, "Sex Differences and Functional Outcome After Intravenous Thrombolysis".

Extracranial Carotid Disease and Effect of Intra-arterial Treatment in Patients With Proximal Anterior Circulation Stroke in MR CLEAN.

The presence of extracranial carotid disease (ECD) is associated with less favorable clinical outcomes a in patients with acute ischemic stroke caused by intracranial proximal occlusion. Acute intra-arterial treatment (IAT) in the setting of extracranial and intracranial lesions is considered challenging, and whether it yields improved outcomes remains uncertain.

Investigations of Carotid Stenosis to Identify Vulnerable Atherosclerotic Plaque and Determine Individual Stroke Risk.

Selection of patients with atherosclerotic carotid stenosis for revascularization is mainly based on the degree of luminal narrowing of the carotid artery. However, identification of other features of plaque apart from the degree of stenosis could enable better selection for intervention if they are also associated with the occurrence of stroke. Before these risk factors can possibly play a role in treatment decisions, their prognostic value needs to be proven. The purpose of this narrative review is to summarize current knowledge regarding the risk factors for stroke in patients with carotid stenosis, how they can be determined, and to what extent they predict stroke, based on recent literature. References for this review were identified by searches of PubMed between 1995 and October, 2016 and references from relevant articles. For each topic in this review different relevant search terms were used. The main search terms were 'carotid stenosis', 'atherosclerosis', 'stroke risk', and 'vulnerable plaque'. Language was restricted to English. The final reference list was generated on the basis of relevance to the topics covered in this review.

Age-Specific Vascular Risk Factor Profiles According to Stroke Subtype.

Ischemic and hemorrhagic stroke are increasingly recognized as heterogeneous diseases with distinct subtypes and etiologies. Information on variation in distribution of vascular risk factors according to age in stroke subtypes is limited. We investigated the prevalence of vascular risk factors in stroke subtypes in relation to age.

Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands).

High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT.

Increasing value and reducing waste in stroke research.

Stroke is a major burden to patients and society, and resources spent on stroke research must be used efficiently and produce good value in terms of improvements in human health. However, many instances of poor value from stroke research funding have resulted from the way in which stroke research topics have been chosen and how studies have been designed, conducted, analysed, regulated, managed, disseminated, or reported. A cooperative effort of European stroke researchers aimed to identify sources of inefficiency and waste, recommend approaches to increase value, and highlight examples of best practice in stroke research. Evidence suggests that progress has been made, but there is room for much improvement; researchers, funders, regulators, and other stakeholders in stroke research might consider these recommendations when planning new research.

Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy.

Complex vascular anatomy might increase the risk of procedural stroke during carotid artery stenting (CAS). Randomized controlled trial evidence that vascular anatomy should inform the choice between CAS and carotid endarterectomy (CEA) has been lacking.

Hyperglycemia predicts poststroke infections in acute ischemic stroke.

To investigate whether admission hyperglycemia predicts poststroke infections and, if so, whether poststroke infections modify the effect of admission hyperglycemia on functional outcome in ischemic stroke.

Sex Differences and Functional Outcome After Intravenous Thrombolysis.

Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)-treated patients, women seem to benefit more. Besides sex differences, age has also a possible effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care.

Do Lacunar Infarcts Have Different Aetiologies? Risk Factor Profiles of Lacunar Infarcts in Deep White Matter and Basal Ganglia: The Second Manifestations of ARTerial Disease-Magnetic Resonance Study.

Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter.

Thrombolysis in Stroke within 30 Minutes: Results of the Acute Brain Care Intervention Study.

Time is brain: benefits of intravenous thrombolysis (IVT) in ischemic stroke last for 4.5 hours but rapidly decrease as time progresses following symptom onset. The goal of the Acute Brain Care (ABC) intervention study was to reduce the door-to-needle time (DNT) to ≤30 minutes by optimizing in-hospital stroke treatment.

Pre-Stroke Use of Beta-Blockers Does Not Lower Post-Stroke Infection Rate: An Exploratory Analysis of the Preventive Antibiotics in Stroke Study.

Stroke-associated infections occur frequently and are associated with unfavorable outcome. Previous cohort studies suggest a protective effect of beta-blockers (BBs) against infections. A sympathetic drive may increase immune suppression and infections.

The effect of anesthetic management during intra-arterial therapy for acute stroke in MR CLEAN.

The aim of the current study was to assess the influence of anesthetic management on the effect of treatment in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN).

Preventive Ceftriaxone in Patients with Stroke Treated with Intravenous Thrombolysis: Post Hoc Analysis of the Preventive Antibiotics in Stroke Study.

The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients who received intravenous thrombolysis (IVT), patients who received ceftriaxone had a significantly better outcome as compared with the control group. This study aimed to gain more insight into the characteristics of these patients.

Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.

Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use.

Statins and poststroke intracerebral hemorrhage: Concern but increasing reassurance.

Association between i.v. thrombolysis volume and door-to-needle times in acute ischemic stroke.

Centralization of intravenous thrombolysis (IVT) for acute ischemic stroke in high-volume centers is believed to improve the door-to-needle times (DNT), but limited data support this assumption. We examined the association between DNT and IVT volume in a large Dutch province. We identified consecutive patients treated with IVT between January 2009 and 2013. Based on annualized IVT volume, hospitals were categorized as low-volume (≤ 24), medium-volume (25-49) or high-volume (≥ 50). In logistic regression analysis, low-volume hospitals were used as reference category. Of 17,332 stroke patients from 11 participating hospitals, 1962 received IVT (11.3 %). We excluded 140 patients because of unknown DNT (n = 86) or in-hospital stroke (n = 54). There were two low-volume (total 101 patients), five medium-volume (747 patients) and four high-volume hospitals (974 patients). Median DNT was shorter in high-volume hospitals (30 min) than in medium-volume (42 min, p < 0.001) and low-volume hospitals (38 min, p < 0.001). Patients admitted to high-volume hospitals had a higher chance of DNT < 30 min (adjusted OR 3.13, 95 % CI 1.70-5.75), lower risk of symptomatic intracerebral hemorrhage (adjusted OR 0.39, 95 % CI 0.16-0.92), and a lower mortality risk (adjusted OR 0.45, 95 % CI 0.21-1.01), compared to low-volume centers. There was no difference in DNT between low- and medium-volume hospitals. Onset-to-needle times (ONT) did not differ between the groups. Hospitals in this Dutch province generally achieved short DNTs. Despite this overall good performance, higher IVT volumes were associated with shorter DNTs and lower complication risks. The ONT was not associated with IVT volume.

Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations.

To determine the genotype-phenotype association in patients with adenosine deaminase-2 (ADA2) deficiency due to identical homozygous R169Q mutations inCECR1 METHODS: We present a case series of nine ADA2-deficient patients with an identical homozygous R169Q mutation. Clinical and diagnostic data were collected and available MRI studies were reviewed. We performed genealogy and haplotype analyses and measured serum ADA2 activity. ADA2 activity values were correlated to clinical symptoms.

Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke.

We compared outcome and complications in patients with stroke treated with intravenous thrombolysis (IVT) who could not live alone without help of another person before stroke (dependent patients) versus independent ones.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial.

Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known.

Clinical Perspective of Carotid Plaque Imaging.

At present, patients with carotid disease are selected for invasive recanalization therapies mainly based on the degree of luminal narrowing and the presence or absence of recent ischemic symptoms. A more sophisticated risk model takes into account other clinical variables, such as age, sex, and the type of recent symptoms, as well as presence of ulcerated plaque. A growing body of evidence shows that noninvasive imaging of the carotid plaque by various methods reliably identifies structural correlates of plaque vulnerability, which are associated with an increased risk of cerebrovascular events.

Use of Antiplatelet Agents Is Associated With Intraplaque Hemorrhage on Carotid Magnetic Resonance Imaging: The Plaque at Risk Study.

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.

Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease.

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, R2 = 0.5, 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, R2 = 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.

Quality of life after surgical decompression for a space-occupying middle cerebral artery infarct: A cohort study.

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.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome.

We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC).

Outcomes are improving for patients with carotid stenosis.

Hospital costs of ischemic stroke and TIA in the Netherlands.

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.

Stenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial.

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.

Unexplained early-onset lacunar stroke and inflammatory skin lesions: Consider ADA2 deficiency.

Cerebral lesions on 7 tesla MRI in patients with sickle cell anemia.

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.