Jeroen Dudink

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (36)116.49 Total impact

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    ABSTRACT: The brain veins of infants are in a complex phase of remodelling in the perinatal period. Magnetic resonance venography and susceptibility-weighted imaging, together with high-resolution Doppler ultrasound, have provided new tools to aid study of venous developmental anatomy and disease. This review aims to provide a comprehensive background of vein development and perinatal venous lesions in preterm and term-born infants, and to encourage further research in both the fetus and the newborn infant, with the aim of preventing or mitigating parenchymal injury related to diseases involving veins.
    Developmental Medicine & Child Neurology 09/2014; · 2.68 Impact Factor
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    ABSTRACT: Neonatal DTI enables quantitative assessment of microstructural brain properties. Although its use is increasing, it is not widely known that vast differences in tractography results can occur, depending on the diffusion tensor estimation methodology used. Current clinical work appears to be insufficiently focused on data quality and processing of neonatal DTI. To raise awareness about this important processing step, we investigated tractography reconstructions of the fornix with the use of several estimation techniques. We hypothesized that the method of tensor estimation significantly affects DTI tractography results.MATERIALS AND METHODS: Twenty-eight DTI scans of infants born <29 weeks of gestation, acquired at 30-week postmenstrual age and without intracranial injury observed, were prospectively collected. Four diffusion tensor estimation methods were applied: 1) linear least squares; 2) weighted linear least squares; 3) nonlinear least squares, and 4) robust estimation of tensors by outlier rejection. Quality of DTI data and tractography results were evaluated for each method.RESULTS: With nonlinear least squares and robust estimation of tensors by outlier rejection, significantly lower mean fractional anisotropy values were obtained than with linear least squares and weighted linear least squares. Visualized quality of tract reconstruction was significantly higher by use of robust estimation of tensors by outlier rejection and correlated with quality of DTI data.CONCLUSIONS: Quality assessment and choice of processing methodology have considerable impact on neonatal DTI analysis. Dedicated acquisition, quality assessment, and advanced processing of neonatal DTI data must be ensured before performing clinical analyses, such as associating microstructural brain properties with patient outcome.
    American Journal of Neuroradiology 01/2014; · 3.17 Impact Factor
  • Tom G Goos, Jeroen Dudink, Irwin K M Reiss
    The Journal of pediatrics 01/2014; · 4.02 Impact Factor
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    ABSTRACT: To determine the prevalence of and to classify ultrasound-proven brain injury during neonatal extracorporeal membrane oxygenation in the Netherlands. Retrospective nationwide study (Rotterdam and Nijmegen), spanning two decades. Level III university hospitals. All neonates who underwent neonatal extracorporeal membrane oxygenation from 1989 to 2010. None. Cranial ultrasound images were reviewed independently by two investigators without knowledge of primary diagnosis, outcome, type of extracorporeal membrane oxygenation, or statistics. The scans were reviewed for lesion type and timing, with the use of a refined classification method for focal brain injury. Extracorporeal membrane oxygenation type was venoarterial in 88%. Brain abnormalities were detected in 17.3%: primary hemorrhage was most frequent (8.8%). Stroke was identified in 5% of the total group, with a notable significant preference for the left hemisphere (in 70%). Lobar hematoma (prevalence 2.2 %) was also significantly left predominant. The incidence of brain injury found with cranial ultrasound in the Netherlands of the patients treated with extracorporeal membrane oxygenation during the neonatal period was 17.3%. Primary hemorrhage was the largest group of lesions, not clearly side-specific except for lobar bleeding, most probably related to changes in venous flow. Arterial ischemic stroke occurred predominant in the left hemisphere.
    Pediatric Critical Care Medicine 10/2013; · 2.35 Impact Factor
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    ABSTRACT: Purpose:To report the incidence of cerebral sinovenous thrombosis (CSVT) in a prospective cohort of preterm infants with a gestational age of less than 29 weeks.Materials and Methods:The local medical ethics review board approved this study, and written parental consent was obtained. Preterm infants with a gestational age of less than 29 weeks who were admitted to the neonatal intensive care unit were prospectively studied with cranial ultrasonography (US). The scan protocol included visualization with color Doppler imaging of the superior sagittal sinus and transverse sinuses through the anterior (8.5-MHz probe) and mastoid (13-MHz probe) fontanelles. When feasible, magnetic resonance imaging was performed to confirm cranial US-diagnosed CSVT. The differences between preterm infants with and without CSVT were analyzed by using Mann-Whitney tests for continuous variables and Fisher exact tests for categorical data.Results:Cranial US was used to document CSVT in 11 of 249 preterm infants with a gestational age of less than 29 weeks. Transverse sinuses were most frequently affected (in all 11 patients with CSVT). All infants with CSVT were asymptomatic. Postnatal age at diagnosis ranged from 5 to 34 days. The mean gestational age was significantly lower in infants with CSVT (25.9 weeks vs 26.8 weeks, P = .038). Of the risk factors studied, only duration of mechanical ventilation was associated with CSVT; it was significantly longer in the CSVT group.Conclusion:Systematic serial cranial US of infants with a gestational age of less than 29 weeks showed a remarkably high incidence of CSVT of 4.4%. Cranial US including color Doppler imaging with scans obtained through the mastoid fontanelle can depict CSVT at an early stage. Treatment of this possibly important condition needs attention.© RSNA, 2013.
    Radiology 08/2013; · 6.34 Impact Factor
  • M M A Raets, J Dudink, P Govaert
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    ABSTRACT: Abstract The germinal matrix (GM) is a richly vascularized, transient layer near the ventricles. It produces neurons and glial cells, and is present in the foetal brain between 8 and 36 weeks of gestation. At 25 weeks, it reaches its maximum volume and subsequently withers. The GM is vulnerable to haemorrhage in preterm infants. This selective vulnerability is explained by limited astrocyte end-feet coverage of microvessels, reduced expression of fibronectin and immature tight junctions. Focal lesions in the neonatal period include haemorrhage, germinolysis and stroke. Such lesions in transient layers interrupt normal brain maturation and induce neurodevelopmental sequelae.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 08/2013; · 1.36 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: To date, studies on neonatal stroke have mainly focused on cortical stroke. We have focused on perforator strokes, noncortical strokes in the arterial vascular perforator area. We sought to identify risk factors and evaluate clinical presentation and neuroimaging findings for neonatal perforator stroke, which seems to be under-recognized. METHODS: All infants admitted to our tertiary intensive care unit in ≈12 years, whose perforator stroke was diagnosed with postnatal brain imaging, were enrolled in this study. Demographic, perinatal, and postnatal data were evaluated. RESULTS: Seventy-nine perforator strokes were detected in 55 patients (28 boys), with a median gestational age of 37 1/7 weeks (range 24 1/7 to 42 1/7 weeks, 25 preterm). Perforator stroke was asymptomatic in most patients (58%). Initial diagnosis was predominantly made with cranial ultrasound (80%) in the first week of life (60%). Risk factors for stroke were present in all cases: maternal, fetal, and perinatal. Likely pathogenic mechanisms were prolonged birth asphyxia (16%), hypoxia or hypotension (15%), embolism (15%), infection (15%), acute blood loss (9%), and birth trauma (9%). CONCLUSIONS: Previously described risk factors for developing neonatal main artery stroke are probably also associated with neonatal perforator stroke. Perforator stroke is often asymptomatic, but cranial ultrasound is a reliable diagnostic tool in diagnosing perforator stroke.
    Stroke 05/2013; · 6.16 Impact Factor
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    ABSTRACT: Advances in neonatal neuroimaging have improved detection of preterm brain injury responsible for abnormal neuromotor and cognitive development. Increasingly sophisticated MR imaging setups allow scanning during early preterm life. In this review, we investigated how brain MR imaging in preterm infants should be timed to best predict long-term outcome. Given the strong evidence that structural brain abnormalities are related to long-term neurodevelopment, MR imaging should preferably be performed at term-equivalent age. Early MR imaging is promising because it can guide early intervention studies and is indispensable in research on preterm brain injury.
    American Journal of Neuroradiology 05/2013; · 3.17 Impact Factor
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    ABSTRACT: Diffusion tensor imaging is a valuable measure in clinical settings to assess diagnosis and prognosis of neonatal brain development. However, obtaining reliable images is not straightforward because of the tissue characteristics of the neonatal brain and the high likelihood of motion artifacts. In this review, we present guidelines on how to acquire DTI data of the neonatal brain and recommend high-quality data acquisition and processing as an essential means to obtain accurate and robust parametric maps. Sudden head movements are problematic for DTI in neonates, and these may lead to incorrect values. We describe strategies to minimize the corrupting effects both in terms of acquisition (eg, more gradient directions) and postprocessing (eg, tensor estimation methods). In addition, tools are described that can help assess whether a dataset is of sufficient quality for further assessment.
    American Journal of Neuroradiology 03/2013; · 3.17 Impact Factor
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    ABSTRACT: Cranial ultrasonography including colour Doppler can detect neonatal carotid flow problems at an early stage, even before symptoms occur. Different pathogeneses can be identified. The condition is more frequent than previously reported. If the circle of Willis is fully developed, this can prevent brain injury even in case of total carotid flow obstruction CONCLUSION: Screening of the carotid artery in critically ill neonates may detect complications of treatment at an early stage.
    Acta Paediatrica 01/2013; · 1.97 Impact Factor
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    ABSTRACT: AIM: To report the clinical presentation, magnetic resonance imaging (MRI) findings, and follow-up data of newborn infants with perinatal arterial ischemic stroke in the territory of the posterior cerebral artery (PCA). METHOD: Data on 18 newborn infants from three neonatal intensive care units (11 males, seven females) with an MRI-confirmed PCA stroke were analysed and reported. Infants were born at a mean gestational age of 38.7 weeks (SD 3.4) with a mean birthweight of 3244g (SD 850). RESULTS: Fourteen infants presented with clinical seizures. Five of these had associated hypoxic-ischemic encephalopathy, four had hypoglycaemia, and five had neither hypoxic-ischemic encephalopathy nor hypoglycaemia. Subclinical seizures were present in one infant with hypoxic-ischemic encephalopathy and one with meningitis. One preterm infant presented with apnoeas and one had hypoxic-ischemic encephalopathy without seizures. Neurodevelopmental follow-up of 17 children at a median age of 36 months (SD 28, range 12-120mo) showed five with a global delay. Two children with additional injury developed postneonatal epilepsy and one child with extensive injury developed hemiplegia. A visual field defect was observed in nine children (six hemianopia, three quadrantanopia). In the 11 children with a second MRI at 3 months, the asymmetry of the optic radiation correlated with the development of a visual field deficit. INTERPRETATION: Outcome after PCA stroke is fairly good, depending on additional brain injury. Follow-up is required, as subsequent visual field defects are frequently observed. Further research will be needed to clarify the role of hypoglycaemia in perinatal arterial ischemic stroke.
    Developmental Medicine & Child Neurology 01/2013; · 2.68 Impact Factor
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    ABSTRACT: Hypoxic-ischemic encephalopathy (HIE) in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC) in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI) was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6) MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI), in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.
    PLoS ONE 01/2013; 8(8):e73031. · 3.53 Impact Factor
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    ABSTRACT: Chorioamnionitis and antenatal glucocorticoids are common exposures for preterm infants and can affect the fetal brain, contributing to cognitive and motor deficits in preterm infants. The effects of antenatal glucocorticoids on the brain in the setting of chorioamnionitis are unknown. We hypothesized that antenatal glucocorticoids would modulate inflammation in the brain and prevent hippocampal and white matter injury after intra-amniotic lipopolysaccharide (LPS) exposure. Time-mated ewes received saline (control), an intra-amniotic injection of 10 mg LPS at 106d GA or 113d GA, maternal intra-muscular betamethasone (0.5 mg/kg maternal weight) alone at 113d GA, betamethasone at 106d GA before LPS or betamethasone at 113d GA after LPS. Animals were delivered at 120d GA (term=150d). Brain structure volumes were measured on T2-weighted MRI images. The subcortical white matter (SCWM), periventricular white matter (PVWM) and hippocampus were analyzed for microglia, astrocytes, apoptosis, proliferation, myelin and pre-synaptic vesicles. LPS and/or betamethasone exposure at different time-points during gestation did not alter brain structure volumes on MRI. Betamethasone alone did not alter any of the measurements. Intra-amniotic LPS at 106d or 113d GA induced inflammation as indicated by increased microglial and astrocyte recruitment which was paralleled by increased apoptosis and hypomyelination in the SCWM and decreased synaptophysin density in the hippocampus. Betamethasone before the LPS exposure at 113d GA prevented microglial activation and the decrease in synaptophysin. Betamethasone after LPS exposure increased microglial infiltration and apoptosis. Intra-uterine LPS exposure for 7d or 14d before delivery induced inflammation and injury in the fetal white matter and hippocampus. Antenatal glucocorticoids aggravated the inflammatory changes in the brain caused by pre-existing intra-amniotic inflammation. Antenatal glucocorticoids prior to LPS reduced the effects of intra-uterine inflammation on the brain. The timing of glucocorticoid administration in the setting of chorioamnionitis can alter outcomes for the fetal brain.
    PLoS ONE 01/2013; 8(12):e81644. · 3.53 Impact Factor
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    ABSTRACT: Cerebral MRI performed on preterm infants at term-equivalent 30 weeks' gestational age (GA) is increasingly performed as part of standard clinical care. We evaluated safety of these early MRI procedures. We retrospectively collected data on patient safety of preterm infants who underwent early MRI scans. Data were collected at fixed times before and after the MRI scan. MRI procedures were carried out according to a comprehensive guideline. A total of 52 infants underwent an MRI scan at 30 weeks' GA. Although no serious adverse events occurred and vital parameters remained stable during the procedure, minor adverse events were encountered in 26 infants (50%). The MRI was terminated in three infants (5.8%) because of respiratory instability. Increased respiratory support within 24 h after the MRI was necessary for 12 infants (23.1%) and was significantly associated with GA, birth weight and the mode of respiratory support. Hypothermia (core temperature < 36°C) occurred in nine infants (17.3%). Temperature dropped significantly after the MRI scan. Minor adverse events after MRI procedures at 30 weeks GA were common and should not be underestimated. A dedicated and comprehensive guideline for MRI procedures in preterm infants is essential.
    Pediatric Radiology 08/2012; 42(10):1205-11. · 1.57 Impact Factor
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    ABSTRACT: In the Netherlands, perinatal asphyxia (severe perinatal oxygen shortage) necessitating newborn resuscitation occurs in at least 200 of the 180-185.000 newly born infants per year. International randomized controlled trials have demonstrated an improved neurological outcome with therapeutic hypothermia. During hypothermia neonates receive sedative, analgesic, anti-epileptic and antibiotic drugs. So far little information is available how the pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs are influenced by post resuscitation multi organ failure and the metabolic effects of the cooling treatment itself. As a result, evidence based dosing guidelines are lacking. This multicenter observational cohort study was designed to answer the question how hypothermia influences the distribution, metabolism and elimination of commonly used drugs in neonatal intensive care. Multicenter cohort study. All term neonates treated with hypothermia for Hypoxic Ischemic Encephalopathy (HIE) resulting from perinatal asphyxia in all ten Dutch Neonatal Intensive Care Units (NICUs) will be eligible for this study. During hypothermia and rewarming blood samples will be taken from indwelling catheters to investigate blood concentrations of several antibiotics, analgesics, sedatives and anti-epileptic drugs. For each individual drug the population PK will be characterized using Nonlinear Mixed Effects Modelling (NONMEM). It will be investigated how clearance and volume of distribution are influenced by hypothermia also taking maturation of neonate into account. Similarly, integrated PK-PD models will be developed relating the time course of drug concentration to pharmacodynamic parameters such as successful seizure treatment; pain assessment and infection clearance. On basis of the derived population PK-PD models dosing guidelines will be developed for the application of drugs during neonatal hypothermia treatment. The results of this study will lead to an evidence based drug treatment of hypothermic neonatal patients. Results will be published in a national web based evidence based paediatric formulary, peer reviewed journals and international paediatric drug references. NTR2529.
    BMC Pediatrics 04/2012; 12:45. · 1.98 Impact Factor
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    ABSTRACT: Familial porencephaly, leukoencephalopathy and small-vessel disease belong to the spectrum of disorders ascribed to dominant mutations in the gene encoding for type IV collagen alpha-1 (COL4A1). Mice harbouring mutations in either Col4a1 or Col4a2 suffer from porencephaly, hydrocephalus, cerebral and ocular bleeding and developmental defects. We observed porencephaly and white matter lesions in members from two families that lack COL4A1 mutations. We hypothesized that COL4A2 mutations confer genetic predisposition to porencephaly, therefore we sequenced COL4A2 in the family members and characterized clinical, neuroradiological and biochemical phenotypes. Genomic sequencing of COL4A2 identified the heterozygous missense G1389R in exon 44 in one family and the c.3206delC change in exon 34 leading to frame shift and premature stop, in the second family. Fragmentation and duplication of epidermal basement membranes were observed by electron microscopy in a c.3206delC patient skin biopsy, consistent with abnormal collagen IV network. Collagen chain accumulation and endoplasmic reticulum (ER) stress have been proposed as cellular mechanism in COL4A1 mutations. In COL4A2 (3206delC) fibroblasts we detected increased rates of apoptosis and no signs of ER stress. Mutation phenotypes varied, including porencephaly, white matter lesions, cerebellar and optic nerve hypoplasia and unruptured carotid aneurysm. In the second family however, we found evidence for additional factors contributing to the phenotype. We conclude that dominant COL4A2 mutations are a novel major risk factor for familial cerebrovascular disease, including porencephaly and small-vessel disease with reduced penetrance and variable phenotype, which might also be modified by other contributing factors.
    European journal of human genetics: EJHG 02/2012; 20(8):844-51. · 3.56 Impact Factor
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    ABSTRACT: Background and aims: Preterm infants are at risk of brain injury with consequent neurodevelopmental impairment. As part of standard clinical care, we screen for possible brain injury by performing cerebral MRI at 30 weeks postmenstrual age. Our aim was to evaluate safety of MRI procedures in this population.
    Pediatric Research 11/2011; · 2.67 Impact Factor
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    ABSTRACT: Background and Aims: Perinatal asphyxia is an important cause of permanent brain injury in term infants. An important neuroimaging indicator of neurodevelopmental prognosis following perinatal asphyxia is the extent of thalamic involvement. However the different patterns of injury seen within thalamus remain unclear. We used diffusion tensor imaging to study these patterns.
    Pediatric Research 11/2011; · 2.67 Impact Factor
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    ABSTRACT: Previous research showed acute diffusion-weighted imaging changes in pulvinar after extensive cortical injury from neonatal stroke. The authors used diffusion tensor imaging (DTI) to see how separate regions of ipsilateral thalamus are directly affected after a primary hit to their connected cortex in neonatal stroke. The authors analysed DTI images of three term infants with acute unilateral cortical arterial ischaemic stroke. Probabilistic tractography was used to define separate thalamic regions of interests (ROIs). The authors evaluated the three eigenvalues (EV) and apparent diffusion coefficient (ADC) values in the ROIs. The ADC and EV in voxels of ROIs placed within the nuclei corresponding to ischaemic cortex were significantly lower than those in the unaffected contralesional thalamic nuclei. Our findings support the concept of acute network injury in neonatal stroke. ADC and EV were altered in specific thalamic regions that corresponded to the specific cortical areas affected by the primary ischaemic injury.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 10/2011; 97(5):F362-4. · 3.45 Impact Factor
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    ABSTRACT: Purpose - Children with syndromic craniosynostosis are at risk for neuropsychological impairment. The cause of this developemental delay is unclear. With this prospective diffusion tensor imaging (DTI) study we aim to assess white matter disorders in patients with syndromic craniosynostosis. Materials and Methods - The Medical Ethics Committee approved this study. A prospective cohort study was performed in 45 children with syndromic craniosynostosis aged six to fourteen years. Data of 7 age-matched controls were available for comparison. For DTI, an echo planar sequence with diffusion gradient (b=1,000s/mm2) applied in 25 non-collinear directions was used. Regions of interest (ROIs) were placed in different white matter structures. Eigenvalues were measured in all ROIs, from which Fractional Anisotropy (FA) were calculated. Results - FA values of the corpus callosum (splenium), the medial cerebellar peduncle, the fornix, the uncinate fasciculus and the mean white matter (MWM), which is given by the mean of the right and left frontal and occipital white matter measurements, were significantly lower in our patients as compared to controls (respectively p< 0,05). Conclusion - DTI measurements of white matter tracts show significant white matter differences between children with craniosynostosis and healthy controls. This could imply the presence of a primary disorder of the white matter micro-architecture causing the developmental delays seen in these patients.
    Plastic Surgery: The Meeting 2011; 09/2011

Publication Stats

205 Citations
116.49 Total Impact Points

Institutions

  • 2008–2014
    • Erasmus MC
      • Department of Neonatology
      Rotterdam, South Holland, Netherlands
  • 2011–2013
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2008–2009
    • Imperial College London
      • Department of Imaging Sciences
      London, ENG, United Kingdom