Rudolf Magnus Institute of Neuroscience

Utrecht, Netherlands

Rudolf Magnus Institute of Neuroscience

Utrecht, Netherlands

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Vlak M.H.M.,Rudolf Magnus Institute of Neuroscience | Vlak M.H.M.,Slotervaart Hospital | Rinkel G.J.E.,Rudolf Magnus Institute of Neuroscience | Greebe P.,Rudolf Magnus Institute of Neuroscience | And 2 more authors.
Stroke | Year: 2013

BACKGROUND AND PURPOSE-: Knowledge about risk factors contributes to understanding the pathophysiological mechanisms that cause intracranial aneurysm rupture and helps to develop possible treatment strategies. We aimed to study lifestyle and personal characteristics as risk factors for the rupture of intracranial aneurysms. METHODS-: We performed a case-control study with 250 patients with an aneurysmal subarachnoid hemorrhage and 206 patients with an unruptured intracranial aneurysm. All patients with an aneurysmal subarachnoid hemorrhage and patients with a unruptured intracranial aneurysm were asked to fill in a structured questionnaire about their lifestyle and medical history. For patients with an unruptured intracranial aneurysm, we also collected data on the indication for imaging. With logistic regression analysis, we identified independent risk factors for aneurysmal rupture. RESULTS-: Reasons for imaging in patients with an unruptured intracranial aneurysm were atherosclerotic disease (23%), positive family history (18%), headache (8%), preventive screening (3%), and other (46%). Factors that increased risk for aneurysmal rupture were smoking (odds ratio, 1.9; 95% confidence interval, 1.2-3.0) and migraine (2.4; 1.1-5.1); hypercholesterolemia decreased this risk (0.4; 0.2-1.0), whereas a history of hypertension did not independently influence the risk. CONCLUSIONS-: Smoking, migraine and, inversely, hypercholesterolemia are independent risk factors for aneurysmal rupture. Data from the questionnaire are insufficient to conclude whether hypercholesterolemia or its treatment with statins exerts a risk-reducing effect. The pathophysiological mechanisms through which smoking and migraine increase the risk of aneurysmal rupture should be investigated in further studies. Although a history of hypertension does not increase risk of rupture, a sudden rise in blood pressure might still trigger aneurysmal rupture. © 2013 American Heart Association, Inc.


Van Beijnum J.,Rudolf Magnus Institute of Neuroscience | Van Beijnum J.,Leiden University | Van Der Worp H.B.,Rudolf Magnus Institute of Neuroscience | Buis D.R.,VU University Amsterdam | And 8 more authors.
JAMA - Journal of the American Medical Association | Year: 2011

Context: Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies. Objectives: To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes. Data Sources: We searched PubMed and EMBASE to March 1, 2011, and handsearched 6 journals from January 2000 until March 2011. Study Selection and Data Extraction: We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration. Data Synthesis: We identified 137 observational studies including 142 cohorts, totaling 13 698 patients and 46 314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n=2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n=9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n=1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00- 1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization. Conclusions: Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified. ©2011 American Medical Association. All rights reserved.


Baarendse P.J.J.,Rudolf Magnus Institute of Neuroscience | Counotte D.S.,University of Maryland Baltimore County | O'Donnell P.,University of Maryland Baltimore County | Vanderschuren L.J.M.J.,Rudolf Magnus Institute of Neuroscience | Vanderschuren L.J.M.J.,University Utrecht
Neuropsychopharmacology | Year: 2013

Social experiences during youth are thought to be critical for proper social and cognitive development. Conversely, social insults during development can cause long-lasting behavioral impairments and increase the vulnerability for psychopathology later in life. To investigate the importance of social experience during the juvenile and early adolescent stage for the development of cognitive control capacities, rats were socially isolated from postnatal day 21 to 42 followed by re-socialization until they reached adulthood. Subsequently, two behavioral dimensions of impulsivity (impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task) and decision making (in the rat gambling task) were assessed. In a separate group of animals, long-lasting cellular and synaptic changes in adult medial prefrontal cortex (PFC) pyramidal neurons were determined following social isolation. Juvenile and early adolescent social isolation resulted in impairments in impulsive action and decision making under novel or challenging circumstances. Moreover, socially isolated rats had a reduced response to enhancement of dopaminergic neurotransmission (using amphetamine or GBR12909) in the 5-CSRTT under challenging conditions. Impulsive choice was not affected by social isolation. These behavioral deficits were accompanied by a loss of sensitivity to dopamine of pyramidal neurons in the medial PFC. Our data show long-lasting deleterious effects of early social isolation on cognitive control and its neural substrates. Alterations in prefrontal cognitive control mechanisms may contribute to the enhanced risk for psychiatric disorders induced by aberrations in the early social environment. © 2013 American College of Neuropsychopharmacology. All rights reserved.


Kanhai D.A.,University Utrecht | Kranendonk M.E.,University Utrecht | Uiterwaal C.S.P.M.,Julius Center for Health science and Primary Care | Van der Graaf Y.,Julius Center for Health science and Primary Care | And 3 more authors.
Obesity Reviews | Year: 2013

Summary: 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 10μg 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. © 2013 International Association for the Study of Obesity.


De Rooij N.K.,Rudolf Magnus Institute of Neuroscience | Greving J.P.,University Utrecht | Rinkel G.J.E.,Rudolf Magnus Institute of Neuroscience | Frijns C.J.M.,Rudolf Magnus Institute of Neuroscience
Stroke | Year: 2013

BACKGROUND AND PURPOSE-: To develop and validate a risk chart for prediction of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on admission characteristics. METHODS-: For derivation of the risk chart, we studied data from 371 prospectively collected consecutive subarachnoid hemorrhage patients with a confirmed aneurysm admitted between 1999 and 2007. For its validation we similarly studied 255 patients admitted between 2007 and 2009. The predictive value of admission characteristics was tested in logistic regression models with delayed cerebral ischemia-related infarction as primary outcome. Procedure-related infarctions were not included. Performance of the models was tested by discrimination and calibration. On the basis of these models, a risk chart was developed for application in clinical practice. RESULTS-: The strongest predictors were clinical condition on admission, amount of blood on computed tomography (both cisternal and intraventricular) and age. A model that combined these 4 predictors had an area under the receiver operating characteristic curve of 0.63 (95% confidence interval, 0.57-0.69). This model improved little by including current smoking and hyperglycemia on admission (area under the receiver operating characteristic curve, 0.65; 95% confidence interval, 0.59-0.71). The risk chart predicted risks of delayed cerebral ischemia-related infarction varying from 12% to 61%. Both low risk (<20% risk) and high risk (>40% risk) were predicted in ≈20% of the patients. Validation confirmed that the discriminative ability was adequate (area under the receiver operating characteristic curve, 0.69; 95% confidence interval, 0.61-0.77). CONCLUSIONS-: Absolute risks of delayed cerebral ischemia-related infarction can be reliably estimated by a simple risk chart that includes clinical condition on admission, amount of blood on computed tomography (both cisternal and intraventricular), and age. © 2013 American Heart Association, Inc.


Horstman P.,Rudolf Magnus Institute of Neuroscience | Linn F.H.H.,Rudolf Magnus Institute of Neuroscience | Linn F.H.H.,University Utrecht | Voorbij H.A.M.,University Utrecht | Rinkel G.J.E.,Rudolf Magnus Institute of Neuroscience
Journal of Neurology | Year: 2012

In patients with sudden severe headache and a negative computed tomography (CT) scan, a lumbar puncture (LP) is performed to rule in or out a subarachnoid haemorrhage (SAH), but this procedure is under debate. In a hospital-based series of 30 patients with sudden headache, a negative CT scan but a positive LP (defined as detection of bilirubin >0.05 at wavelength 458 nm), we studied the chance of harbouring an aneurysm and the clinical outcome. Aneurysms were found in none of both patients who presented within 3 days, in 8 of the 18 (44%) who presented within 4-7 days and in 5 of the 10 (50%) who presented within 8-14 days. Of the 13 patients with an aneurysm, 3 (23%) had poor outcome. In patients who present late after sudden headache, the yield in terms of aneurysms is high in those who have a positive lumbar puncture. In patients with an aneurysm as cause of the positive lumbar puncture, outcome is in the same range as in SAH patients admitted in good clinical condition. © Springer-Verlag 2011.


Van Lutterveld R.,University Utrecht | Van Lutterveld R.,Rudolf Magnus Institute of Neuroscience | Diederen K.M.J.,University Utrecht | Diederen K.M.J.,Rudolf Magnus Institute of Neuroscience | And 4 more authors.
Human Brain Mapping | Year: 2014

Background: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia and can severely disrupt behavior and decrease quality of life. Identification of areas with high functional connectivity (so-called hub regions) that are associated with the predisposition to hallucinate may provide potential targets for neuromodulation in the treatment of AVH. Methods: Resting-state fMRI scans during which no hallucinations had occurred were acquired from 29 nonpsychotic individuals with AVH and 29 matched controls. These nonpsychotic individuals with AVH provide the opportunity to study AVH without several confounds associated with schizophrenia, such as antipsychotic medication use and other symptoms related to the illness. Hub regions were identified by assessing weighted connectivity strength and betweenness centrality across groups using a permutation analysis. Results: Nonpsychotic individuals with AVH exhibited increased functioning as hub regions in the temporal cortices and the posterior cingulate/precuneus, which is an important area in the default mode network (DMN), compared to the nonhallucinating controls. In addition, the right inferior temporal gyrus, left paracentral lobule and right amygdala were less important as a hub region in the AVH group. Conclusions: These results suggest that the predisposition to hallucinate may be related to aberrant functioning of the DMN and the auditory cortices. © 2013 Wiley Periodicals, Inc.


Kahn R.S.,Rudolf Magnus Institute of Neuroscience | Keefe R.S.E.,Duke University
JAMA Psychiatry | Year: 2013

Schizophrenia is currently classified as a psychotic disorder. This article posits that this emphasis on psychosis is a conceptual fallacy that has greatly contributed to the lack of progress in our understanding of this illness and hence has hampered the development of adequate treatments. Not only have cognitive and intellectual underperformance consistently been shown to be risk factors for schizophrenia, several studies have found that a decline in cognitive functioning precedes the onset of psychosis by almost a decade. Although the question of whether cognitive function continues to decline after psychosis onset is still debated, it is clear that cognitive function in schizophrenia is related to outcome and little influenced by antipsychotic treatment. Thus, our focus on defining (and preventing) the disorder on the basis of psychotic symptoms may be too narrow. Not only should cognition be recognized as the core component of the disorder, our diagnostic efforts should emphasize the changes in cognitive function that occur earlier in development. Putting the focus back on cognition may facilitate finding treatments for the illness before psychosis ever emerges.


Creemers H.,Academic Medical Center Amsterdam | Veldink J.H.,Rudolf Magnus Institute of Neuroscience | Grupstra H.,Academic Medical Center Amsterdam | Nollet F.,Academic Medical Center Amsterdam | And 2 more authors.
Neurology | Year: 2014

Objectives: To study the effect of case management on quality of life, caregiver strain, and perceived quality of care (QOC) in patients with amyotrophic lateral sclerosis (ALS) and their caregivers. Methods: We conducted a multicenter cluster randomized controlled trial with the multidisciplinary ALS care team as the unit of randomization. During 12 months, patients with ALS and their caregivers received case management plus usual care or usual care alone. Outcome measures were the 40-item ALS Assessment Questionnaire (ALSAQ-40), Emotional Functioning domain (EF); the Caregiver Strain Index (CSI); and the QOC score. These measures were assessed at baseline and at 4, 8, and 12 months. Results: Case management resulted in no changes in ALSAQ-40 EF, CSI, or QOC from baseline to 12 months. ALSAQ-40 EF scores in both groups were similar at baseline and did not change over time (p = 0.331). CSI scores in both groups increased significantly (p < 0.0001). Patients with ALS from both groups rated their perceived QOC at baseline with a median score of 8, which did not change significantly during follow-up. Conclusion: Within the context of multidisciplinary ALS care teams, case management appears to confer no benefit for patients with ALS or their caregivers. Classification of evidence: This study provides Class III evidence that case management in addition to multidisciplinary ALS care does not significantly improve health-related quality of life of patients with ALS. © 2013 American Academy of Neurology.


Van Liempt S.,Research Center Military Mental Health Care | Van Liempt S.,Rudolf Magnus Institute of Neuroscience | Van Zuiden M.,Research Center Military Mental Health Care | Westenberg H.,Rudolf Magnus Institute of Neuroscience | And 2 more authors.
Depression and Anxiety | Year: 2013

Background A significant proportion of soldiers return from deployment with symptoms of fatigue, sleep difficulties, and posttraumatic complaints. Disrupted sleep has been proposed as a contributing factor for the development of posttraumatic stress disorder (PTSD). This study investigates the impact of impaired sleep and nightmares before deployment on the development of PTSD symptoms. Method We collected reports on insomnia symptoms and nightmares in 453 Dutch service members prior to military deployment to Afghanistan. PTSD symptoms were assessed at 6 months postdeployment. The predictive value of insomnia symptoms and nightmares on the development of PTSD symptoms was assessed with a logistic regression analyses, in which was controlled for predeployment mood and anxiety symptoms. Results Self-reported predeployment nightmares predicted PTSD symptoms at 6 months (odds ratio 2.992, 95% confidence interval (CI) 1.096-8.551, P <.05), while predeployment insomnia complaints did not (odds ratio 0.976, 95% CI 0.862-1.155, P >.05). Conclusion In conclusion, this prospective longitudinal cohort study indicates that the existence of predeployment nightmares is associated with an increased risk for the development of PTSD symptoms. Nightmares may be related to hampered fear extinction memory consolidation, which has been associated with REM sleep. © 2013 Wiley Periodicals, Inc.

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