Heeze, Netherlands
Heeze, Netherlands

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Ryvlin P.,University Claude Bernard Lyon 1 | Gilliam F.G.,Pennsylvania State University | Nguyen D.K.,University of Notre Dame | Colicchio G.,Catholic University of the Sacred Heart | And 12 more authors.
Epilepsia | Year: 2014

Objective To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long-term health-related quality of life (HRQoL). Methods PuLsE (Open Prospective Randomized Long-term Effectiveness) was a prospective, randomized, parallel-group, open-label, and long-term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n = 112) received VNS + BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory-89 total score; QOLIE-89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES-D), Neurological Disorders Depression Inventory-Epilepsy scale (NDDI-E), Clinical Global Impression-Improvement scale (CGI-I), Adverse Event Profile (AEP), and antiepileptic drug (AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n = 362. Results for n = 96 who had baseline and at least one follow-up QOLIE-89 assessment (from months 3-12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints. Results Significant between-group differences in favor of VNS + BMP were observed regarding improvement in HRQoL, seizure frequency, and CGI-I score (respective p-values < 0.05, 0.03, and 0.01). More patients in the VNS + BMP group (43%) reported adverse events (AEs) versus BMP group (21%) (p = 0.01), a difference reflecting primarily mostly transient AEs related to VNS implantation or stimulation. No significant difference between treatment groups was observed for changes in CES-D, NDDI-E, AEP, and AED load. Significance VNS therapy as a treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant improvement in HRQoL compared with BMP alone. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. © 2014 The Authors Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.


Snoeijen-Schouwenaars F.M.,Kempenhaeghe | Van Deursen K.C.,Maastricht University | Tan I.Y.,Kempenhaeghe | Verschuure P.,Laboratory for Clinical Chemistry and Pharmacology | And 2 more authors.
Pediatric Neurology | Year: 2015

Background Children with epilepsy and intellectual disability have an increased risk of vitamin D deficiency. In this patient group, it is neither clear which factors are associated with the level of 25-hydroxyvitamin D nor what the therapeutic results are when Dutch guidelines are followed. Methods This retrospective study included 30 patients who, in October 2012, were residents of the children's wards of a tertiary epilepsy center in The Netherlands (Kempenhaeghe). From November 2012 onward they received cholecalciferol supplementation in doses that met or exceeded Dutch guidelines. At baseline, after 6, and 15 months, serum 25-hydroxyvitamin D concentration was measured. Results At baseline, the vitamin D status in 11 (36.7%) residents was found to be deficient, in 10 (33.3%) to be insufficient and in 9 (30.0%) sufficient. Supplementation dose, diet, body mass index, intellectual disability, and mobility were significantly associated with baseline 25-hydroxyvitamin D concentrations. The mean 25-hydroxyvitamin D concentration increased significantly from 57.40 ± 22.00 nmol/L at baseline to 89.47 ± 26.77 nmol/L after 15 months (P < 0.001). In spite of supplementation ranging from 400 to 1200 IU/day, 64% of the residents in the deficient category and 30% of those with an insufficient level at baseline failed to attain a sufficient vitamin D status after 15 months. Conclusions Not all residents reached a sufficient vitamin D status after supplementation at least equal to the amount recommended by the Dutch guidelines. In a high-risk population, such as our residents, we advise monitoring 25-hydroxyvitamin D concentrations, adjusting supplementation accordingly and following patients to ensure they reach sufficiency. © 2015 Elsevier Inc. All rights reserved.


PubMed | Kempenhaeghe., Maastricht University, Kempenhaeghe. Electronic address and Laboratory for Clinical Chemistry & Pharmacology
Type: Journal Article | Journal: Pediatric neurology | Year: 2015

Children with epilepsy and intellectual disability have an increased risk of vitamin D deficiency. In this patient group, it is neither clear which factors are associated with the level of 25-hydroxyvitamin D nor what the therapeutic results are when Dutch guidelines are followed.This retrospective study included 30 patients who, in October 2012, were residents of the childrens wards of a tertiary epilepsy center in The Netherlands (Kempenhaeghe). From November 2012 onward they received cholecalciferol supplementation in doses that met or exceeded Dutch guidelines. At baseline, after 6, and 15 months, serum 25-hydroxyvitamin D concentration was measured.At baseline, the vitamin D status in 11 (36.7%) residents was found to be deficient, in 10 (33.3%) to be insufficient and in 9 (30.0%) sufficient. Supplementation dose, diet, body mass index, intellectual disability, and mobility were significantly associated with baseline 25-hydroxyvitamin D concentrations. The mean 25-hydroxyvitamin D concentration increased significantly from 57.40 22.00 nmol/L at baseline to 89.47 26.77 nmol/L after 15 months (P < 0.001). In spite of supplementation ranging from 400 to 1200 IU/day, 64% of the residents in the deficient category and 30% of those with an insufficient level at baseline failed to attain a sufficient vitamin D status after 15 months.Not all residents reached a sufficient vitamin D status after supplementation at least equal to the amount recommended by the Dutch guidelines. In a high-risk population, such as our residents, we advise monitoring 25-hydroxyvitamin D concentrations, adjusting supplementation accordingly and following patients to ensure they reach sufficiency.


Van Houdt P.J.,Epilepsy Center Kempenhaeghe | Van Houdt P.J.,VU University Amsterdam | Ossenblok P.P.W.,Kempenhaeghe | Boon P.A.J.M.,Epilepsy Center Kempenhaeghe | And 4 more authors.
Human Brain Mapping | Year: 2010

EEG correlated functional MRI (EEG-fMRI) allows the delineation of the areas corresponding to spontaneous brain activity, such as epileptiform spikes or alpha rhythm. A major problem of fMRI analysis in general is that spurious correlations may occur because fMRI signals are not only correlated with the phenomena of interest, but also with physiological processes, like cardiac and respiratory functions. The aim of this study was to reduce the number of falsely detected activated areas by taking the variation in physiological functioning into account in the general linear model (GLM). We used the photoplethysmogram (PPG), since this signal is based on a linear combination of oxy- and deoxyhemoglobin in the arterial blood, which is also the basis of fMRI. We derived a regressor from the variation in pulse height (VIPH) of PPG and added this regressor to the GLM. When this regressor was used as predictor it appeared that VIPH explained a large part of the variance of fMRI signals acquired from five epilepsy patients and thirteen healthy volunteers. As a confounder VIPH reduced the number of activated voxels by 30% for the healthy volunteers, when studying the generators of the alpha rhythm. Although for the patients the number of activated voxels either decreased or increased, the identification of the epileptogenic zone was substantially enhanced in one out of five patients, whereas for the other patients the effects were smaller. In conclusion, applying VIPH as a confounder diminishes physiological noise and allows a more reliable interpretation of fMRI results. © 2009 Wiley-Liss, Inc.


Boets B.,Catholic University of Leuven | Boets B.,Massachusetts Institute of Technology | Verhoeven J.,Kempenhaeghe | Verhoeven J.,Catholic University of Leuven | And 2 more authors.
Journal of Autism and Developmental Disorders | Year: 2015

We investigated low-level auditory spectral and temporal processing in adolescents with autism spectrum disorder (ASD) and early language delay compared to matched typically developing controls. Auditory measures were designed to target right versus left auditory cortex processing (i.e. frequency discrimination and slow amplitude modulation (AM) detection versus gap-in-noise detection and faster AM detection), and to pinpoint the task and stimulus characteristics underlying putative superior spectral processing in ASD. We observed impaired frequency discrimination in the ASD group and suggestive evidence of poorer temporal resolution as indexed by gap-in-noise detection thresholds. These findings question the evidence of enhanced spectral sensitivity in ASD and do not support the hypothesis of superior right and inferior left hemispheric auditory processing in ASD. © 2014, Springer Science+Business Media New York.


PubMed | Kempenhaeghe, Stichting Epilepsie Instellingen Nederland and TU Eindhoven
Type: | Journal: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology | Year: 2017

Diagnostic value and efficacy of re-interpretation of previous EEGs in 100 patients admitted to a tertiary epilepsy center with EEG results conflicting with the clinical diagnosis after the first visit.EEGs were reclassified. A matched control group was included to assess the efficiency of the re-interpretation process. Efficacy was assessed by questionnaires and costs as number of technician hours needed.In 85 patients the previous EEG conclusion was known. In 43 the conclusion was altered. In 23 the epileptic activity changed from positive to negative (17) or the reverse (6). In 15 the focus changed (7 originally classified as generalized epileptic activity). In 5 the syndrome changed. 57% of the re-interpretation group needed no extra EEG afterwards. 96% of the re-interpretations were considered useful by requesting and 72% by not involved neurologists. The average time per EEG technologist per patient was 8,81h in controls and 5,40 in the re-interpretation group.In 43 from the 85 patients (51%) re-interpretation of controversial EEGs led to a different opinion. The re-interpretations were useful and less time consuming, compared to new EEGs in controls.Re-interpretation of controversial EEGs is useful and cost effective.


Van Liempt S.,Research Center Military Mental Healthcare | Van Liempt S.,Rudolf Magnus Institute of Neuroscience | Vermetten E.,Research Center Military Mental Healthcare | Lentjes E.,University Utrecht | And 2 more authors.
Psychoneuroendocrinology | Year: 2011

Background: Healthy sleep facilitates the consolidation of newly acquired memories. Although patients with posttraumatic stress disorder (PTSD) often complain of sleep disturbances and memory deficits, the interrelatedness of these symptoms is not well understood. Sleep may be disturbed in PTSD by increased awakenings during sleep, which has been associated with decreased growth hormone (GH) secretion. We conducted a controlled study in which we assessed sleep fragmentation, nocturnal secretion of GH, and memory consolidation in patients with PTSD. Methods: While sleep EEG was being monitored, 13 veterans with PTSD, 15 trauma controls (TC) and 15 healthy controls (HC) slept with an iv catheter, through which blood was collected every 20. min from 23:00. h to 08:00. h. Declarative memory encoding was assessed with the 15 word task before sleep, and consolidation was assessed the next morning by a free recall. Results: Sleep was more fragmented in patients with PTSD, with more awakenings in the first half of the night (p<0.05). Plasma levels of GH during the night were significantly decreased in PTSD compared with HC (p<0.05). Furthermore, GH secretion and awakenings were independent predictors for delayed recall, which was lower in PTSD compared to HC (p<0.05). Conclusions: These data show that PTSD is associated with increased awakenings during sleep and decreased nocturnal GH secretion. Furthermore, decreased GH secretion may be related to sleep fragmentation and both variables may exert a negative effect on sleep dependent memory consolidation. © 2011 Elsevier Ltd.


EEG-correlated functional MRI (EEG-fMRI) visualizes brain regions associated with interictal epileptiform discharges (IEDs). This technique images the epileptiform network, including multifocal, superficial and deeply situated cortical areas. To understand the role of EEG-fMRI in presurgical evaluation, its results should be validated relative to a gold standard. For that purpose, EEG-fMRI data were acquired for a heterogeneous group of surgical candidates (n=16) who were later implanted with subdural grids and strips (ECoG). The EEG-fMRI correlation patterns were systematically compared with brain areas involved in IEDs ECoG, using a semi-automatic analysis method, as well as to the seizure onset zone, resected area, and degree of seizure freedom. In each patient at least one of the EEG-fMRI areas was concordant with an interictally active ECoG area, always including the early onset area of IEDs in the ECoG data. This confirms that EEG-fMRI reflects a pattern of onset and propagation of epileptic activity. At group level, 76% of the BOLD regions that were covered with subdural grids, were concordant with interictally active ECoG electrodes. Due to limited spatial sampling, 51% of the BOLD regions were not covered with electrodes and could, therefore, not be validated. From an ECoG perspective it appeared that 29% of the interictally active ECoG regions were missed by EEG-fMRI and that 68% of the brain regions were correctly identified as inactive with EEG-fMRI. Furthermore, EEG-fMRI areas included the complete seizure onset zone in 83% and resected area in 93% of the data sets. No clear distinction was found between patients with a good or poor surgical outcome: in both patient groups, EEG-fMRI correlation patterns were found that were either focal or widespread. In conclusion, by comparison of EEG-fMRI with interictal invasive EEG over a relatively large patient population we were able to show that the EEG-fMRI correlation patterns are spatially accurate at the level of neurosurgical units (i.e. anatomical brain regions) and reflect the underlying network of IEDs. Therefore, we expect that EEG-fMRI can play an important role for the determination of the implantation strategy. Copyright © 2013 Elsevier Inc. All rights reserved.


van der Kruijs S.J.M.,Kempenhaeghe | Bodde N.M.G.,Kempenhaeghe | Aldenkamp A.P.,Kempenhaeghe
Acta Neurologica Belgica | Year: 2011

Misdiagnosis of patients with psychogenic non-epileptic seizures (PNES) as having epilepsy is a clinical relevant problem. Considerable problems for the patients, such as unnecessary anticonvulsant medication use and delay of suitable therapy, as well as a considerable economic burden are involved. Furthermore, after the diagnosis of PNES is confirmed, there is a lack of scientific evidence about the most efficient treatment for PNES. Evaluation of contributing factors is necessary. These factors should be implemented in explanatory models for the occurrence of PNES, which should be employed in diagnosis and treatment. Recent evidence suggests a role of deficiencies in neuronal information processing in multiple mental conditions. Although the focus in PNES research over the last two decades primarily has been on differential diagnosis and psychological and environmental factors, abnormalities in psychophysiological characteristics might also be involved in PNES. This review focuses on neurobiological substrates of PNES and dissociation, a trait which is often associated with PNES, to explore whether deviant information processing is involved in the aetiology of PNES. All studies examining the relationship between psychophysiological parameters and PNES have an exploratory character. However, the results suggest that neurophysiological characteristics, such as brain activity as visualized by functional MRI, cardiovascular measurements and neuroendocrine functioning, may be abnormal in patients with PNES. Future investigations should therefore elucidate the exact role of neurophysiological abnormalities in the aetiology of PNES.


van Houdt P.J.,Kempenhaeghe | van Houdt P.J.,VU University Amsterdam | Ossenblok P.P.W.,Kempenhaeghe | Colon A.J.,Kempenhaeghe | And 4 more authors.
Brain Topography | Year: 2015

Spatial independent component analysis (ICA) is increasingly being used to extract resting-state networks from fMRI data. Previous studies showed that ICA also reveals independent components (ICs) related to the seizure onset zone. However, it is currently unknown how these epileptic ICs depend on the presence of interictal epileptic discharges (IEDs) in the EEG. The goal of this study was to explore the relation between ICs obtained from fMRI epochs during the occurrence of IEDs in the EEG and those without IEDs. fMRI data sets with co-registered EEG were retrospectively selected of patients from whom the location of the epileptogenic zone was confirmed by outcome of surgery (n = 8). The fMRI data were split into two epochs: one with IEDs visible in scalp EEG and one without. Spatial ICA was applied to the fMRI data of each part separately. The maps of all resulting components were compared to the resection area and the EEG–fMRI correlation pattern by computing a spatial correlation coefficient to detect the epilepsy-related component. For all patients, except one, there was a remarkable resemblance between the epilepsy-related components selected during epochs with IEDs and those without IEDs. These findings suggest that epilepsy-related ICs are not dependent on the presence of IEDs in scalp EEG. Since these epileptic ICs showed partial overlap with resting-state networks of healthy volunteers (n = 10), our study supports the need for new ways to classify epileptic ICs. © 2014, Springer Science+Business Media New York.

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