Johan S H Vles

Maastricht Universitair Medisch Centrum, Maestricht, Limburg, Netherlands

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Publications (66)164.42 Total impact

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    ABSTRACT: Little is known about the long-term effects of Continuous intrathecal Baclofen (CITB) therapy in non-ambulant children with intractable spastic Cerebral Palsy (CP). To determine whether short-term beneficial effects of CITB therapy are present at the long-term, and whether caregivers would choose CITB therapy for their child again considering the advantages and disadvantages encountered over the years. Long-term follow-up data were obtained of the children whom had previously participated in a RCT on CITB by the Dutch Study Group on Spasticity. Quality of life (QoL) was assessed by the Child Health Questionnaire (CHQ), current satisfaction with CITB was measured by use of a Visual Analogue Scale regarding previously set treatment goals, functioning in daily living was determined by a questionnaire concerning functioning of the child, and possible detrimental effects of CITB therapy encountered over the years were noted. All data were acquired via interview of the caregivers. All 17 children of the former trial participated in this study. Previously identified significant positive effects on pain (CHQ 46.8 vs. 74.38, p = 0.002; VAS 2.4 vs. 8.01, p = 0.02), ease of care (VAS 2.0 vs. 7.26, p = 0.00), and mental health (CHQ 67.2 vs. 75.94, p = 0.010) were still present at the end of the trial. Novel significant positive effects were noted at six to nine years follow-up, i.e. significantly improved scores on the Parent Impact - Emotional subscale (CHQ 66.0 vs. 78.2, p = 0.008), Parent Impact - Time subscale (CHQ 68.9 vs. 91.72, p = 0.002), and the Physical Summary (CHQ 17.6 vs. 27.4, p = 0.019) compared to baseline. Ninety-four percent of the caregivers would choose CITB treatment again for their child again. The beneficial effects of CITB are present at the long term and caregiver satisfaction is high.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 07/2013; · 2.01 Impact Factor
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    ABSTRACT: Based on the assumption that children with spinal dysraphism are exposed to a large amount of ionising radiation for diagnostic purposes, our objective was to estimate this exposure, expressed in cumulative effective dose. Retrospective cohort study. The Netherlands. 135 patients with spinal dysraphism and under 18 years of age treated at our institution between 1991 and 2010. A total of 5874 radiological procedures were assessed of which 2916 (49.6%) involved ionising radiation. Mean cumulative effective dose of a child with spinal dysraphism during childhood was 23 mSv, while the individual cumulative effective dose ranged from 0.1 to 103 mSv. Although direct radiography accounted for 81.7% of examinations, the largest contributors to the cumulative effective dose were fluoroscopic examinations (40.4% of total cumulative effective dose). Exposure to ionising radiation and associated cancer risk were lower than expected. Nevertheless, the use of ionising radiation should always be justified and the medical benefits should outweigh the risk of health detriment, especially in children.
    Archives of Disease in Childhood 07/2013; · 3.05 Impact Factor
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    ABSTRACT: BACKGROUND: In clinical practice, Rolandic epilepsy is in many cases associated with developmental language impairment. However, from the literature it is unclear exactly which domains are affected; A wide variety of investigations are reported that each provide a different representation of language performance in these patients. AIMS: The aim of this study is to compare performance on the language domains between children with Rolandic epilepsy and healthy controls. METHODS: Prospective study of children with Rolandic epilepsy compared to healthy controls. 25 children (mean age 136.6 months, SD 23.0) with Rolandic epilepsy and 25 age-matched healthy controls were tested on their language function using the CELF-4 (Clinical evaluation of Language Fundamentals, Dutch edition). The healthy control were not matched regard to other important factors, particularly educational attainment and co-morbidity. Expressive language, receptive language, language content, language structure and language working memory were tested. RESULTS: In children with Rolandic epilepsy, the core language score was significant lower compared with healthy controls. They scored specifically lower on the receptive language index and language content index (both p = 0.002). A trend towards decreased expressive language index was observed (p = 0.054). Language structure and language working memory were in the normal range. CONCLUSION: Language was found to be impaired in children with typical Rolandic epilepsy. Especially semantic language processing including receptive language and language content was significantly impaired. The common denominator of these functions is semantic language processing.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 02/2013; · 2.01 Impact Factor
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    ABSTRACT: Purpose:  Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls. Methods:  Thirty-two children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired. Key Findings:  Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Significance:  Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad-range cognitive impairments in children with FLE.
    Epilepsia 12/2012; · 3.96 Impact Factor
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    ABSTRACT: Please also see the Letter on this paper by Robinson on page 195 of this issue.
    Developmental Medicine & Child Neurology 12/2012; · 2.68 Impact Factor
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    ABSTRACT: In a rat model of global fetal and perinatal asphyxia, we investigated if asphyxia and long-lasting brain tolerance to asphyxia (preconditioning) are mediated by modifications in inflammatory cytokines and ceramide metabolism genes in prefrontal cortex, hippocampus and caudate-putamen at the age of 8months. Most significant changes were found in prefrontal cortex, with reduced LAG1 homolog ceramide synthase 1 expression after both types of asphyxia. Additionally, sphingosine kinase 1 was upregulated in those animals that experienced the combination of fetal and perinatal asphyxia (preconditioning), suggesting increased cell proliferation. While cytokine levels are normal, levels of ceramide genes were modulated both after fetal and perinatal asphyxia in the adult prefrontal cortex. Moreover, the combination of two subsequent asphyctic insults provides long-lasting neuroprotection in the prefrontal cortex probably by maintaining normal apoptosis and promoting cell proliferation. Better understanding of the effects of asphyxia on ceramide metabolism will help to understand the changes leading to brain tolerance and will open opportunities for the development of new neuroprotective therapies.
    Journal of neuroimmunology 10/2012; · 2.84 Impact Factor
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    ABSTRACT: Objectives: The vagus nerve has important immunological and anti-inflammatory actions that might be relevant to the beneficial effects of vagus nerve stimulation (VNS). Therefore, we conducted an exploratory study on VNS effects on cytokine levels in plasma and cerebrospinal fluid of children suffering from refractory epilepsy. Moreover, as predictors of the response are lacking, we also aimed to determine if cytokine changes predict the clinical response. Methods: VNS was performed according to a randomized double-blind design: plasma levels were compared between patients who received 20 weeks of high output (therapeutic) (n = 21) or low output (active control) stimulation (n = 20). Thereupon, all patients received high output stimulation for another 19 weeks; levels during this period were compared to baseline. Interictal interleukin-1β, interleukin-6, and interleukin-10 were determined by ELISA. Results: No significant changes were found between high and low output groups and between the last 19 weeks of stimulation and baseline. Changes in interleukin-1β correlated with improved IQ (τ = 0.42, p < 0.01). Lower baseline plasma levels of interleukin-6 were associated with more seizure frequency reduction [R(2) = 0.105 (1, 35), p = 0.050]. Conclusion: Interictal cytokine levels were not altered by VNS but baseline interleukin-6 predicted the clinical response. In the future, patient selection may be aided by determination of the cytokine profile of the patient.
    NeuroImmunoModulation 10/2012; 19(6):352-358. · 1.84 Impact Factor
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    ABSTRACT: Cognitive impairment is the most common comorbidity in children with epilepsy, but its pathophysiology and predisposing conditions remain unknown. Clinical epilepsy characteristics are not conclusive in determining cognitive outcome. Because many children with epilepsy do not have macrostructural magnetic resonance imaging (MRI) abnormalities, the underlying substrate for cognitive impairment may be found at the microstructural or functional level. In the last two decades, new MRI techniques have been developed that have the potential to visualize microstructural or functional abnormalities associated with cognitive impairment. These include volumetric MRI, voxel-based morphometry (VBM), diffusion tensor imaging (DTI), MR spectroscopy (MRS), and functional MRI (fMRI). All of these techniques have shed new light on various aspects associated with, or underlying, cognitive impairment, although their use in epilepsy has been limited and focused mostly on adults. Therefore, in this review, the use of all these different MRI techniques to unravel cognitive impairment in epilepsy is discussed both in adults and children with epilepsy. Volumetric MRI and VBM have revealed significant volume losses in the area of the seizure focus as well as in distant areas. DTI adds evidence of loss of integrity of connections from the seizure focus to distant areas as well as between distant areas. MRS and fMRI have shown impaired function both in the area of the seizure focus as well as in distant structures. For this review we have compiled and compared findings from the various techniques to conclude that cognitive impairment in epilepsy results from a network disorder in which the (micro)structures as well as the functionality can be disturbed.
    Epilepsia 08/2012; 53(10):1690-9. · 3.96 Impact Factor
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    ABSTRACT: BACKGROUND/AIMS: In addition to effects on seizure frequency in intractable epilepsy, multiple studies report benefits of vagus nerve stimulation (VNS) on behavioural outcomes and quality of life. The present study aims to investigate the effects of VNS on cognition, mood in general, depression, epilepsy-related restrictions and psychosocial adjustment in children with intractable epilepsy, as well as the relation between these effects and seizure reduction. METHODS: We conducted a randomized, active-controlled, double-blinded, add-on study in 41 children (age 4-18) with medically refractory epilepsy. We performed cognitive and behavioural testing at baseline (12 weeks), at the end of the blinded phase (20 weeks) in children receiving either high-output or low-output (active control) stimulation, and at the end of the open label phase (19 weeks) with all children receiving high-output stimulation. Seizure frequency was recorded using seizure diaries. RESULTS: VNS did not have a negative effect on cognition nor on psychosocial adjustment. At the end of the follow-up phase we noted an improvement of mood in general and the depression subscale for the entire group, unrelated to a reduction of seizure frequency. At the end of the blinded phase a ≥50% reduction of seizure frequency occurred in 16% of the high-stimulation group and 21% of the low-stimulation group. At the end of the open-label follow-up phase, 26% of the children experienced a seizure frequency reduction of 50% or more (responders). CONCLUSIONS: VNS has additional beneficial effects in children with intractable epilepsy. As opposed to anti-epileptic drugs, there are no negative effects on cognition. Moreover, we observed an improvement of mood in general and depressed feelings in particular, irrespective of a reduction in seizure frequency. These beneficial effects should be taken into account when deciding whether to initiate or continue VNS treatment in these children.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 08/2012; · 2.01 Impact Factor
  • European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 08/2012; · 2.01 Impact Factor
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    ABSTRACT: Frontal Lobe Epilepsy (FLE) is the second most frequent type of partial epilepsy and its onset is generally in childhood. Though cognitive and behavioural impairments have been described as co-morbid disorders in epilepsy, their extent in FLE, particularly in children, remains unknown. In this study, we assess cognitive skills and behaviour in a cohort of paediatric FLE patients. We measured the performance of 71 children with cryptogenic FLE on intelligence tests, neuropsychological tests, and behavioural questionnaires. Age-dependent normative values were used for reference. Results were related to epilepsy-factors including age at epilepsy onset, duration of epilepsy, seizure frequency, localisation of the epileptic focus and drug load. Paediatric FLE patients performed worse on intellectual and neuropsychological tests compared to reference values, and had a delay in school achievement. The performance of patients was typically worse on tasks measuring visual-spatial functions, memory, psychomotor speed and alertness. High seizure frequency was associated with lower scores on the arithmetic subtest of the intelligence scale; the other epilepsy-factors had no statistically significant influence on intelligence test or neuropsychological test outcome. Behavioural problems included attention problems, anxiety and internalising behaviour. These were not significantly related to epilepsy-factors. Children with cryptogenic FLE show a broad range of cognitive and behavioural impairments, compared to reference values. While high seizure frequency may affect performance on selected cognitive measures, other epilepsy-factors do not seem to influence cognition and behaviour. Study of micro-structural or functional brain abnormalities that underlie these cognitive and behavioural impairments are warranted.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 06/2012; 16(6):707-15. · 2.01 Impact Factor
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    ABSTRACT: Educational difficulties or even severe cognitive deterioration is seen in many childhood epilepsy syndromes. Many of those cognitive deficits are related directly to the brain disorder underlying the epilepsy syndrome. However, in other types of epilepsy, the epileptic seizures and/or epileptiform activity can be the dominant factor. This is especially unknown for the more "subtle" short nonconvulsive seizure types. For this reason, we analyzed a new cohort of children. A cross-sectional study of 188 children with epilepsy. Electroencephalography (EEG)-video recordings and cognitive testing were performed simultaneously. The results of children with short nonconvulsive seizures during a 2-h testing session were compared with all children with epilepsy without seizures during the 2-h cognitive testing session and with controls without epilepsy. In a second analysis the cognitive effects of frequency of epileptiform EEG discharges were analyzed. The cognitive effects of short nonconvulsive seizures were large, ranging from 0.5 to 1 standard deviation and concerned global cognitive function, speed of central information processing, and memory function. In children without seizures during cognitive testing, the occurrence of frequent epileptiform discharges showed more subtle effects. These effects were independent from the occurrence of short nonconvulsive seizures. We concluded that although the effect is less pronounced in number of areas involved and magnitude, the type of association between frequent epileptiform activity (>1% of the time) and cognitive function in children with epilepsy is comparable to the association between short nonconvulsive seizures and cognitive function.
    Epilepsia 05/2012; 53(6):1051-9. · 3.96 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the effects of vagus nerve stimulation (VNS) in children with intractable epilepsy on seizure frequency and severity and in terms of tolerability and safety. In this study, the first randomized active controlled trial of its kind in children, 41 children (23 males; 18 females; mean age at implantation 11y 2mo, SD 4y 2mo, range 3y 10mo-17y 8mo) were included. Thirty-five participants had localization-related epilepsy (25 symptomatic; 10 cryptogenic), while six participants had generalized epilepsy (four symptomatic; two idiopathic). During a baseline period of 12 weeks, seizure frequency and severity were recorded using seizure diaries and the adapted Chalfont Seizure Severity Scale (NHS3), after which the participants entered a blinded active controlled phase of 20 weeks. During this phase, half of the participants received high-output VNS (maximally 1.75mA) and the other half received low-output stimulation (0.25mA). Finally, all participants received high-output stimulation for 19 weeks. For both phases, seizure frequency and severity were assessed as during the baseline period. Overall satisfaction and adverse events were assessed by semi-structured interviews. At the end of the randomized controlled blinded phase, seizure frequency reduction of 50% or more occurred in 16% of the high-output stimulation group and in 21% of the low-output stimulation group (p=1.00). There was no significant difference in the decrease in seizure severity between participants in the stimulation groups. Overall, VNS reduced seizure frequency by 50% or more in 26% of participants at the end of the add-on phase The overall seizure severity also improved (p<0.001). VNS is a safe and well-tolerated adjunctive treatment of epilepsy in children. Our results suggest that the effect of VNS on seizure frequency in children is limited. However, the possible reduction in seizure severity and improvement in well-being makes this treatment worth considering in individual children with intractable epilepsy.
    Developmental Medicine & Child Neurology 04/2012; 54(9):855-61. · 2.68 Impact Factor
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    Johan S H Vles
    Developmental Medicine & Child Neurology 11/2011; 53(11):1061; author reply 1062-3. · 2.68 Impact Factor
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    ABSTRACT: An association between impaired school performance and rolandic epilepsy is frequently reported. Language outcome, in particular, seems to be affected, although rolandic epilepsy originates from the motor-sensory cortex. In this study we tried to find a correlation between locomotion problems and language impairment. In this noncontrolled, open, clinical cohort study of 48 children with rolandic epilepsy, a 24-hour EEG and a neuropsychological assessment were obtained for all children. Children with rolandic epilepsy had a significant delay in reading skills (reading words: mean=6 months, SD=11.9, P<0.002; reading sentences: mean=8.6 months, SD=12.7, P<0.001), compared with the healthy population. There was a significant correlation between problems in motor development and delays in reading skills (reading words: r=-0.426, P=0.006; reading sentences: r=-0.343, P=0.03). Reading performance is impaired in children with rolandic epilepsy. Reading of sentences is more impaired than reading of words. There is a significant correlation between problems in motor development and language, suggesting their interaction at the level of the cortex.
    Epilepsy & Behavior 09/2011; 22(3):527-31. · 2.06 Impact Factor
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    ABSTRACT: Tight filum syndrome (TFS) is caused by a thick (abnormal T1 MRI), shortened (low-lying conus), or non-elastic filum (strictly normal MRI). We carefully analyzed children treated for suspect TFS with or without radiological abnormalities. Twenty-five children, operated between 2002 and 2009, were retrospectively identified. All children had been evaluated by a multidisciplinary team preoperatively. Symptoms, signs and diagnostic test results were categorized (neurologic, urologic, orthopedic, dermatologic) and compared pre- and one year postoperatively. Normal MR was defined as conus medullaris (CM) at or above mid-body L2 and filum diameter less than 2 mm. Occult TFS (OTFS) was defined as TFS with normal MR. Demographics: 17 girls, 8 boys, age 2-18 years, including 11 syndromal children. Clinical presentation: all children had problems in the neurologic category and at least one other category: urologic (n = 17), orthopedic (n = 21), and dermatologic (n = 11). MR findings: low-lying CM (n = 14) including 2 with thick filum, normal CM but fatty filum (n = 2), strictly normal (n = 9). Clinical outcome one year postoperatively: neurologic 20 improved, 5 stabilized; urologic 13 improved, 3 stabilized, 1 worsened; orthopedic (8 children presenting with scoliosis) 3 improved, 4 stabilized, 1 worsened. All children with OTFS (n = 9) improved in at least one and 8 improved in all affected categories. Children with strong clinical suspicion for TFS (≥ 2 affected categories) with or without abnormal MR findings will likely benefit from surgery. In such cases we suggest a detailed full spine MR, a multidisciplinary diagnostic work-up, and eventual untethering through an interlaminar microsurgical approach.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 08/2011; 16(2):103-17. · 2.01 Impact Factor
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    ABSTRACT: Vagus nerve stimulation (VNS) is a moderately effective adjunctive treatment for patients suffering from medically refractory epilepsy and is explored as a treatment option for several other disorders. The present review provides a critical appraisal of the studies on VNS in animal models of seizures and epilepsy. So far, these studies mostly applied short-term VNS in seizure models, demonstrating that VNS can suppress and prevent seizures and affect epileptogenesis. However, the mechanism of action is still largely unknown. Moreover, studies with a clinically more relevant setup where VNS is chronically applied in epilepsy models are scarce. Future directions for research and the application of this technology in animal models of epilepsy are discussed.
    Experimental Neurology 08/2011; 230(2):167-75. · 4.65 Impact Factor
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    Journal of Neurosurgery Pediatrics 07/2011; 8(1):112-3; author reply 113-4. · 1.63 Impact Factor
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    ABSTRACT: The cerebellum, primarily considered a pure motor structure, is increasingly considered to play a role in behaviour and cognition. In a similar manner, there is increasing evidence that the basal ganglia are involved in non-motor processes. Recently a direct connection between the cerebellum and the basal ganglia has been shown to exist. High-frequency stimulation (HFS) of the subthalamic nucleus (STN) has become an accepted treatment in advanced Parkinson's disease (PD). We performed HFS of the STN in rats to evaluate the neuronal activation in the deep cerebellar nuclei (DCbN) using c-Fos immunohistochemistry. We found an increased c-Fos expression in the DCbN. Previously, we have shown that STN HFS in rats leads to decreased impulsive behaviour and our findings now suggest a link with increased DCbN activity. This is in line with our previous work showing that decreased DCbN activity is accompanied by disruptive behaviour. We suggest that the DCbN play a role in the selection of relevant information on which a behavioural response is based. The connection between the cerebellum and the basal ganglia may imply a role for the cerebellum in behavioural aspects of disorders of the basal ganglia.
    Neuroscience Letters 06/2011; 496(2):111-5. · 2.03 Impact Factor
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    ABSTRACT: Frontal lobe epilepsy (FLE) is considered the second most common type of the localization-related epilepsies of childhood. Still, the etiology of FLE in children, its impact on cognitive functioning and behavior, as well as the response to antiepileptic drug treatment in children has not been sufficiently studied. This review focuses on these aspects of FLE in childhood, and reveals that FLE in childhood is most often cryptogenic, and impacts on a broad range of cognitive functions. The nature and severity of cognitive deficits are highly variable, although impaired attention and executive functions are most frequent. Young age at seizure onset is the only potential risk factor for poor cognitive outcome that has been consistently reported. The behavioral disturbances associated with FLE are also highly variable, although attention deficit/hyperactivity disorder seems most frequent. In 40% of children with FLE satisfactory seizure control could not be achieved. This is a higher percentage than reported for the general population of children with epilepsy. Therefore, pediatric FLE, even if cryptogenic in nature, is frequently complicated by impairment of cognitive function, behavioral disturbances, and therapy-resistance. Given the impact of these complications, there is a need for studies of the etiology of frontal lobe epilepsy-associated cognitive and behavioral disturbances, as well as pharmacotherapy-resistance.
    Epilepsia 05/2011; 52(5):849-56. · 3.96 Impact Factor

Publication Stats

813 Citations
164.42 Total Impact Points

Institutions

  • 1997–2013
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 2002–2012
    • Maastricht University
      • • Neurologie
      • • Neurologie
      • • Psychiatrie en Neuropsychologie
      Maastricht, Provincie Limburg, Netherlands
  • 2007–2011
    • Kempenhaeghe
      Heeze, North Brabant, Netherlands
    • Ghent University
      Gand, Flanders, Belgium