H. Delye | Radboudumc Nijmegen - The Netherlands (original) (raw)

Papers by H. Delye

Journal of Neuropathology & Experimental Neurology, 2002

Mutations of the SOD1 gene underlie 1 form of familial amyotrophic lateral sclerosis (ALS). Their... more Mutations of the SOD1 gene underlie 1 form of familial amyotrophic lateral sclerosis (ALS). Their pathogenic mechanism remains uncertain, but is thought to involve oxidative stress and abnormal protein aggregation, 2 processes known to induce heat shock proteins (HSPs). We studied the expression of 3 HSPs (␣B-crystallin, HSP27, and HSP70) in transgenic mice overexpressing human mutant (G93A and G37R) SOD1, using a combination of immunohistochemistry and immunoblotting. Quantitative Western blot analysis demonstrated ␣B-crystallin and HSP27 to be upregulated in the spinal cord of mutant SOD1 mice compared to mice overexpressing wild-type SOD1. HSP70 levels were normal. Immunocytochemical studies of the ventral horn of the spinal cord demonstrated HSP27 to be localized in the nucleus of neurons and glial cells in presymptomatic and early symptomatic animals, where it often was punctate in pattern. In the later stages of the disease, HSP27 was predominantly present in the cytoplasm of reactive glial cells. The early nuclear localization was confirmed by Western blot analysis of spinal cord nuclear and cytoplasmic fractions. In contrast to HSP27, ␣B-crystallin was localized exclusively in the cytoplasm of reactive glial cells.

European Spine Journal, 2009

Journal of Neurosurgery: Pediatrics, 2014

Object The authors conducted a study to compare the complication rate (CR) of pediatric neurosurg... more Object The authors conducted a study to compare the complication rate (CR) of pediatric neurosurgical procedures in a general neurosurgery department to the CRs that are reported in the literature and to establish a baseline of CR for further targeted improvement of quality neurosurgical care. Methods The authors analyzed the prospectively collected data from a complication registration of 1000 consecutive pediatric neurosurgical procedures in 581 patients from the beginning of the registration in January 2004 through August 2008. A pediatric neurosurgeon was involved in 50.5% of the procedures. All adverse events (AEs) from induction of anesthesia until 30 days postoperatively were recorded. Results Overall, 229 complications were counted in 202 procedures. The overall CR was 20.2%, with a 2.7% intraoperative CR and a 17.5% postoperative CR. Tumor surgery was associated with the highest CR (32.7%), followed by CSF disorders (21.8%). The mortality rate was 0.3%. An unplanned return ...

Several head injury criteria, some of which are generally accepted whereas others are newly propo... more Several head injury criteria, some of which are generally accepted whereas others are newly proposed, are implemented and applied to multibody accident simulations of typical bicycle-car accidents. The main goal is to establish the importance of car - and bicycle speed and relative car-bicycle trajectory for accident reconstruction studies. For this purpose, Madymo, cyclist and car models are used in a parametric sensitivity analysis study. Head injury criteria include the HIC, maximum change in rotational velocity of the head and peak rotational head acceleration. Injury parameters are investigated for 30 different cases of frontal and sideways collisions. For cyclist speeds ranging from 10 to 30 km/h and car speeds from 20 to 50 km/h, HIC values range from 200 up to 2500. Maximum change in head rotational velocity ranges from 20 to 60 rad/s and peak rotational acceleration from 4500 to 22000 rad/s². In general, sideways impacts lead to higher values for all head injury criteria. T...

Child's Nervous System, 2019

Purpose Posthaemorrhagic ventricular dilatation in preterm infants is primarily treated using tem... more Purpose Posthaemorrhagic ventricular dilatation in preterm infants is primarily treated using temporising measures, of which the placement of a ventricular access device (VAD) is one option. Permanent shunt dependency rates are high, though vary widely. In order to improve the treatment burden and lower shunt dependency rates, we implemented several changes over the years. One of these changes involves the setting of the surgery from general anaesthesia in the OR to local anaesthesia in bed at the neonatal intensive care unit (NICU), which may seem counterintuitive to many. In this article, we describe our surgical technique and present the results of this regimen and compare it to our previous techniques. Methods Retrospective study of a consecutive series of 37 neonates with posthaemorrhagic ventricular dilatation (PHVD) treated using a VAD, with a cohort I (n = 13) treated from 2004 to 2008 under general anaesthesia in the OR, cohort II (n = 11) treated from 2009 to 2013 under ge...

Pediatric Anesthesia, 2018

The aim of this study was to evaluate pre-, intra-, and postoperative anesthetic parameters in en... more The aim of this study was to evaluate pre-, intra-, and postoperative anesthetic parameters in endoscopic strip craniectomy in order to improve anesthesiological care. Materials and Methods: This is a retrospective patient cohort study of our first 121 patients treated by endoscopic strip craniectomy. Preoperative as well as intra-and postoperative anesthesiological and neurological parameters were analyzed. Furthermore, the need for intensive care unit admission, blood loss, and blood transfusion rate were measured. Results: The mean age of patients was 3.9 months (standard deviation = 1) at a mean weight of 6.3 kg (standard deviation = 1.3). Comorbidity was registered in 13 (11%) patients of which 5 had syndrome-related comorbidities. Mean duration of anesthesia was 131 minutes (standard deviation = 32). One hundred and sixteen patients were induced by mask induction with sevoflurane and 5 patients were induced intravenously. In 10 patients, mild intraoperative hypothermia (between 35 and 36 degrees Celsius) occurred. The mean estimated blood loss was 35.4 mL (standard deviation = 28.9) and blood transfusion rate was 21.5%. Brief and small intraoperative oxygen saturation drops were common during this study. No indication for venous air embolism was found based on endtidal CO 2. Postoperative temperature above 38 degrees Celsius occurred 16 times and benign deviations in postoperative cardiopulmonary parameters occurred in 17 patients. Postoperative pain management was mainly established by paracetamol and low-dose morphine when necessary. No postoperative neurological symptoms were reported and no deaths occurred. Conclusion: These patients had a relatively short intraoperative course with stable vital parameters during surgery. We report a low incidence of significant venous air embolism, a blood transfusion rate of 21% and only minor perioperative disturbances in vital parameters.

Journal of Neurosurgery: Pediatrics, 2017

OBJECTIVEAfter endoscopic third ventriculostomy (ETV), some patients develop recurrent symptoms o... more OBJECTIVEAfter endoscopic third ventriculostomy (ETV), some patients develop recurrent symptoms of hydrocephalus. The optimal treatment for these patients is not clear: repeat ETV (re-ETV) or CSF shunting. The goals of the study were to assess the effectiveness of re-ETV relative to initial ETV in pediatric patients and validate the ETV success score (ETVSS) for re-ETV.METHODSRetrospective data of 624 ETV and 93 re-ETV procedures were collected from 6 neurosurgical centers in the Netherlands (1998–2015). Multivariable Cox proportional hazards modeling was used to provide an adjusted estimate of the hazard ratio for re-ETV failure relative to ETV failure. The correlation coefficient between ETVSS and the chance of re-ETV success was calculated using Kendall’s tau coefficient. Model discrimination was quantified using the c-statistic. The effects of intraoperative findings and management on re-ETV success were also analyzed.RESULTSThe hazard ratio for re-ETV failure relative to ETV fa...

Journal of Cranio-Maxillofacial Surgery, 2016

Craniosynostosis represents premature closure of cranial sutures. Prevalence is approximately 3.1... more Craniosynostosis represents premature closure of cranial sutures. Prevalence is approximately 3.1-6.4 in 10.000 live births, which is reportedly rising. This epidemiologic study aims to provide insight into this rise through an accurate description of the prevalence, exploring regional variation and change over time. The Dutch Association for Cleft Palate and Craniofacial Anomalies was consulted to identify patients with craniosynostosis born between 2008 and 2013. Data were verified using data provided by all hospitals that treated these patients. The following data were collected: date of birth, gender, diagnosis and postal code. Previously reported data from 1997 until 2007 were included to assess for change in prevalence over the years. Between 2008 and 2013 759 patients with craniosynostosis were born in the Netherlands. Prevalence of craniosynostosis was 7.2 per 10.000 live births. Sagittal synostosis was the most common form (44%). Poisson regression analysis showed a significant mean annual increase of prevalence of total craniosynostosis (+12.5%), sagittal (+11.7%) and metopic (+20.5%) synostosis from 1997 to 2013. The prevalence of craniosynostosis is 7.2 per 10.000 live born children in the Netherlands. Prevalence of total craniosynostosis, sagittal and metopic suture synostosis has risen significantly from 1997 until 2013, without obvious cause.

Journal of Cranio-Maxillofacial Surgery, 2016

An evaluation of our first 111 consecutive cases of non-syndromic endoscopically assisted cranios... more An evaluation of our first 111 consecutive cases of non-syndromic endoscopically assisted craniosynostosis surgery (EACS) followed by helmet therapy. Retrospective analysis of a prospective registration database was performed. Age, duration of surgery, length of hospital stay, blood loss, transfusion rate, cephalic index and duration of helmet therapy were evaluated. An online questionnaire was used to evaluate the burden of the helmet therapy for the child and parents. 111 EAC procedures were performed: 64 for scaphocephaly, 34 for trigonocephaly and13 for anterior plagiocephaly. The mean age at the time of surgery was 3.9 (±1) months, mean surgical time was 58 (±18) minutes, mean blood loss was 34 (±28) ml, transfusion rate was 22% (n = 26), mean duration of postoperative helmet therapy was 10 (±2.5) months, mean preoperative and postoperative CI were respectively 0.67(±0.057) and 0.72 (±0.062) in scaphocephalic patients and the mean length of hospital stay was 2.6 (±1) days. The burden of the helmet therapy for the child and his family was deemed very low. EACS for non-syndromic patients shows low morbidity rates, short surgical time, short length of hospital stay, little blood loss and low need for blood transfusion and is associated with satisfying cosmetic results.

Introduction: Today, no objective standardized planning procedure exists for the preoperative pla... more Introduction: Today, no objective standardized planning procedure exists for the preoperative planning of open cranial vault reconstruction of patients suffering from craniosynostosis. The use of a normative skull model, which will serve as a reference, will enhance the standardized planning procedure. Since no normative skull models of the Dutch population exist yet, a method was developed to create normative skull models of this population. Methods: Steps include the creation of volumetric data and threshold determination, creation of mesh data, registration, rendering and normalization. Results: A normative skull model represented as point cloud was created based on the CT scans of three patients. Conclusion: The presented method enables the creation of normative skull models, using three CT data sets containing skull images. Therefore, this method is suitable for the creation of normative skull models of the Dutch population.

Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the association of ... more Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the association of large and/or multiple congenital melanocytic nevi (CMN) of the skin with melanocytic lesions of the leptomeninges, including melanocytosis. Leptomeningeal melanocytosis carries a poor prognosis once neurological symptoms develop. Despite surgery, which is often not radical, few other treatment options exist. Recently, it was demonstrated that early embryonic, post-zygotic somatic mutations in the NRAS gene are implicated in the pathogenesis of NCM. In this report, we present a 13-year-old boy with NCM and progressive symptomatic leptomeningeal melanocytosis. A somatic NRAS Q61K mutation was present in both CMN as well as the melanocytosis. Despite repeated surgery, the patient showed clinical progression. Therefore, treatment with MEK162, a MEK inhibitor, was started on compassionate use base. The patient died only five days later, i.e. too early to expect a clinical effect of MEK162 therapy. We therefore studied the effect of MEK162 at the protein level in the leptomeningeal tumor by immunohistochemical and Western Blot analyses using Ki67 and pERK antibodies. We observed lower MIB-1 expression and lower pERK expression in the post-treatment samples compared to pre-treatment, suggesting a potential effect of MEK inhibiting therapy. Further studies are needed to determine whether MEK inhibitors can effectively target NRAS-mutated symptomatic NCM, a rare but potentially fatal disease.

International Journal of Oral and Maxillofacial Surgery, 2019

Insight into the growth and development of the normal newborn cranial shape is essential to monit... more Insight into the growth and development of the normal newborn cranial shape is essential to monitor cranial development, to detect and diagnose abnormal skull shapes, and for the long-term follow-up of craniosynostosis surgery. The aim of this study was to analyse the growth pattern of the cranial shape of infants during the first years of life using 3D stereophotogrammetry and 3D computed tomography (CT) with advanced 3D evaluation techniques. A large set of 3D photographs (n=199) and CT scans (n=183), taken between ages 0 and 54 months, was collected. Cranial shapes with artefacts and asymmetries were removed. Total volumes and intracranial volumes were obtained, as well as 3D and 2D measurements, including the cranial width, cranial length, cranial index, and suture lengths. Growth maps were created for all modalities to indicate 3D growth over time. For the final analysis, a total of 130 3D photographs, 94 hard tissue CT scans, and 76 soft tissue CT scans were used. 3D and 2D measures, volumes, growth maps, and growth animations were obtained. A non-uniform growth was revealed by the 3D growth maps. This study addresses the need for normative cranial evolution data to monitor healthy cranial development and for detection, follow-up, and treatment planning in craniosynostosis.

Acta Neurochirurgica, 2019

Background The surgeons’ estimate of the extent of resection (EOR) shows little accuracy in previ... more Background The surgeons’ estimate of the extent of resection (EOR) shows little accuracy in previous literature. Considering the developments in surgical techniques of glioblastoma (GBM) treatment, we hypothesize an improvement in this estimation. This study aims to compare the EOR estimated by the neurosurgeon with the EOR determined using volumetric analysis on the post-operative MR scan. Methods Pre- and post-operative tumor volumes were calculated through semi-automatic volumetric assessment by three observers. Interobserver agreement was measured using intraclass correlation coefficient (ICC). A univariate general linear model was used to study the factors influencing the accuracy of estimation of resection percentage. Results ICC was high for all three measurements: pre-operative tumor volume was 0.980 (0.969–0.987), post-operative tumor volume 0.974 (0.961–0.984), and EOR 0.947 (0.917–0.967). Estimation of EOR by the surgeon showed moderate accuracy and agreement. Multivariab...

Plastic and Reconstructive Surgery - Global Open, 2019

Plastic and Reconstructive Surgery - Global Open, 2019

Conclusion: Natural improvement was observed, which advocates reassessment in a selected group. S... more Conclusion: Natural improvement was observed, which advocates reassessment in a selected group. Short-term neurocognitive evaluation can be indicative for the future, but further longitudinal follow-up is necessary to determine whether there is a neurocognitive indication for operation or whether it is just an aesthetic procedure. This knowledge is important, in order to better involve parents in the shared decision making process of this possible high risk procedure.

Surgical Innovation, 2018

The implementation of augmented reality (AR) in image-guided surgery (IGS) can improve surgical i... more The implementation of augmented reality (AR) in image-guided surgery (IGS) can improve surgical interventions by presenting the image data directly on the patient at the correct position and in the actual orientation. This approach can resolve the switching focus problem, which occurs in conventional IGS systems when the surgeon has to look away from the operation field to consult the image data on a 2-dimensional screen. The Microsoft HoloLens, a head-mounted AR display, was combined with an optical navigation system to create an AR-based IGS system. Experiments were performed on a phantom model to determine the accuracy of the complete system and to evaluate the effect of adding AR. The results demonstrated a mean Euclidean distance of 2.3 mm with a maximum error of 3.5 mm for the complete system. Adding AR visualization to a conventional system increased the mean error by 1.6 mm. The introduction of AR in IGS was promising. The presented system provided a solution for the switchi...

Scientific reports, Jan 20, 2018

Virtual planning of open cranial vault reconstruction is used to simulate and define an pre-opera... more Virtual planning of open cranial vault reconstruction is used to simulate and define an pre-operative plan for craniosynostosis surgery. However, virtual planning techniques are subjective and dependent on the experience and preferences of the surgical team. To develop an objective automated 3D pre-operative planning technique for open cranial vault reconstructions, we used curvature maps for the shape comparison of the patient's skull with an age-specific reference skull. We created an average skull for the age-group of 11-14 months. Also, we created an artificial test object and selected a cranial CT-scan of an 11 months old trigonocephaly patient as test case. Mesh data of skulls were created using marching cubes and raycasting. Curvature maps were computed using quadric surface fitting. The shape comparison was tested for the test object and the average skull. Finally, shape comparison was performed for the trigonocephalic skull with the average skull. Similar shapes and the...

International journal of oral and maxillofacial surgery, Jan 6, 2017

Craniosynostosis is a congenital defect which can result in abnormal cranial morphology. Three di... more Craniosynostosis is a congenital defect which can result in abnormal cranial morphology. Three dimensional (3D) stereophotogrammetry is potentially an ideal technique for the evaluation of cranial morphology and diagnosis of craniosynostosis because it is fast and harmless. This study presents a new method for objective characterization of the morphological abnormalities of scaphocephaly and trigonocephaly patients using 3D photographs of patients and healthy controls. Sixty 3D photographs of healthy controls in the age range of 3-6 months were superimposed and scaled. Principal component analysis (PCA) was applied to find the mean cranial shape and the cranial shape variation in this normal population. 3D photographs of 20 scaphocephaly and 20 trigonocephaly patients were analysed by this PCA model to test whether cranial deformities of scaphocephaly and trigonocephaly patients could be objectively identified. PCA was used to find the mean cranial shape and the cranial shape variat...

Journal of Neuropathology & Experimental Neurology, 2002

Mutations of the SOD1 gene underlie 1 form of familial amyotrophic lateral sclerosis (ALS). Their... more Mutations of the SOD1 gene underlie 1 form of familial amyotrophic lateral sclerosis (ALS). Their pathogenic mechanism remains uncertain, but is thought to involve oxidative stress and abnormal protein aggregation, 2 processes known to induce heat shock proteins (HSPs). We studied the expression of 3 HSPs (␣B-crystallin, HSP27, and HSP70) in transgenic mice overexpressing human mutant (G93A and G37R) SOD1, using a combination of immunohistochemistry and immunoblotting. Quantitative Western blot analysis demonstrated ␣B-crystallin and HSP27 to be upregulated in the spinal cord of mutant SOD1 mice compared to mice overexpressing wild-type SOD1. HSP70 levels were normal. Immunocytochemical studies of the ventral horn of the spinal cord demonstrated HSP27 to be localized in the nucleus of neurons and glial cells in presymptomatic and early symptomatic animals, where it often was punctate in pattern. In the later stages of the disease, HSP27 was predominantly present in the cytoplasm of reactive glial cells. The early nuclear localization was confirmed by Western blot analysis of spinal cord nuclear and cytoplasmic fractions. In contrast to HSP27, ␣B-crystallin was localized exclusively in the cytoplasm of reactive glial cells.

European Spine Journal, 2009

Journal of Neurosurgery: Pediatrics, 2014

Object The authors conducted a study to compare the complication rate (CR) of pediatric neurosurg... more Object The authors conducted a study to compare the complication rate (CR) of pediatric neurosurgical procedures in a general neurosurgery department to the CRs that are reported in the literature and to establish a baseline of CR for further targeted improvement of quality neurosurgical care. Methods The authors analyzed the prospectively collected data from a complication registration of 1000 consecutive pediatric neurosurgical procedures in 581 patients from the beginning of the registration in January 2004 through August 2008. A pediatric neurosurgeon was involved in 50.5% of the procedures. All adverse events (AEs) from induction of anesthesia until 30 days postoperatively were recorded. Results Overall, 229 complications were counted in 202 procedures. The overall CR was 20.2%, with a 2.7% intraoperative CR and a 17.5% postoperative CR. Tumor surgery was associated with the highest CR (32.7%), followed by CSF disorders (21.8%). The mortality rate was 0.3%. An unplanned return ...

Several head injury criteria, some of which are generally accepted whereas others are newly propo... more Several head injury criteria, some of which are generally accepted whereas others are newly proposed, are implemented and applied to multibody accident simulations of typical bicycle-car accidents. The main goal is to establish the importance of car - and bicycle speed and relative car-bicycle trajectory for accident reconstruction studies. For this purpose, Madymo, cyclist and car models are used in a parametric sensitivity analysis study. Head injury criteria include the HIC, maximum change in rotational velocity of the head and peak rotational head acceleration. Injury parameters are investigated for 30 different cases of frontal and sideways collisions. For cyclist speeds ranging from 10 to 30 km/h and car speeds from 20 to 50 km/h, HIC values range from 200 up to 2500. Maximum change in head rotational velocity ranges from 20 to 60 rad/s and peak rotational acceleration from 4500 to 22000 rad/s². In general, sideways impacts lead to higher values for all head injury criteria. T...

Child's Nervous System, 2019

Purpose Posthaemorrhagic ventricular dilatation in preterm infants is primarily treated using tem... more Purpose Posthaemorrhagic ventricular dilatation in preterm infants is primarily treated using temporising measures, of which the placement of a ventricular access device (VAD) is one option. Permanent shunt dependency rates are high, though vary widely. In order to improve the treatment burden and lower shunt dependency rates, we implemented several changes over the years. One of these changes involves the setting of the surgery from general anaesthesia in the OR to local anaesthesia in bed at the neonatal intensive care unit (NICU), which may seem counterintuitive to many. In this article, we describe our surgical technique and present the results of this regimen and compare it to our previous techniques. Methods Retrospective study of a consecutive series of 37 neonates with posthaemorrhagic ventricular dilatation (PHVD) treated using a VAD, with a cohort I (n = 13) treated from 2004 to 2008 under general anaesthesia in the OR, cohort II (n = 11) treated from 2009 to 2013 under ge...

Pediatric Anesthesia, 2018

The aim of this study was to evaluate pre-, intra-, and postoperative anesthetic parameters in en... more The aim of this study was to evaluate pre-, intra-, and postoperative anesthetic parameters in endoscopic strip craniectomy in order to improve anesthesiological care. Materials and Methods: This is a retrospective patient cohort study of our first 121 patients treated by endoscopic strip craniectomy. Preoperative as well as intra-and postoperative anesthesiological and neurological parameters were analyzed. Furthermore, the need for intensive care unit admission, blood loss, and blood transfusion rate were measured. Results: The mean age of patients was 3.9 months (standard deviation = 1) at a mean weight of 6.3 kg (standard deviation = 1.3). Comorbidity was registered in 13 (11%) patients of which 5 had syndrome-related comorbidities. Mean duration of anesthesia was 131 minutes (standard deviation = 32). One hundred and sixteen patients were induced by mask induction with sevoflurane and 5 patients were induced intravenously. In 10 patients, mild intraoperative hypothermia (between 35 and 36 degrees Celsius) occurred. The mean estimated blood loss was 35.4 mL (standard deviation = 28.9) and blood transfusion rate was 21.5%. Brief and small intraoperative oxygen saturation drops were common during this study. No indication for venous air embolism was found based on endtidal CO 2. Postoperative temperature above 38 degrees Celsius occurred 16 times and benign deviations in postoperative cardiopulmonary parameters occurred in 17 patients. Postoperative pain management was mainly established by paracetamol and low-dose morphine when necessary. No postoperative neurological symptoms were reported and no deaths occurred. Conclusion: These patients had a relatively short intraoperative course with stable vital parameters during surgery. We report a low incidence of significant venous air embolism, a blood transfusion rate of 21% and only minor perioperative disturbances in vital parameters.

Journal of Neurosurgery: Pediatrics, 2017

OBJECTIVEAfter endoscopic third ventriculostomy (ETV), some patients develop recurrent symptoms o... more OBJECTIVEAfter endoscopic third ventriculostomy (ETV), some patients develop recurrent symptoms of hydrocephalus. The optimal treatment for these patients is not clear: repeat ETV (re-ETV) or CSF shunting. The goals of the study were to assess the effectiveness of re-ETV relative to initial ETV in pediatric patients and validate the ETV success score (ETVSS) for re-ETV.METHODSRetrospective data of 624 ETV and 93 re-ETV procedures were collected from 6 neurosurgical centers in the Netherlands (1998–2015). Multivariable Cox proportional hazards modeling was used to provide an adjusted estimate of the hazard ratio for re-ETV failure relative to ETV failure. The correlation coefficient between ETVSS and the chance of re-ETV success was calculated using Kendall’s tau coefficient. Model discrimination was quantified using the c-statistic. The effects of intraoperative findings and management on re-ETV success were also analyzed.RESULTSThe hazard ratio for re-ETV failure relative to ETV fa...

Journal of Cranio-Maxillofacial Surgery, 2016

Craniosynostosis represents premature closure of cranial sutures. Prevalence is approximately 3.1... more Craniosynostosis represents premature closure of cranial sutures. Prevalence is approximately 3.1-6.4 in 10.000 live births, which is reportedly rising. This epidemiologic study aims to provide insight into this rise through an accurate description of the prevalence, exploring regional variation and change over time. The Dutch Association for Cleft Palate and Craniofacial Anomalies was consulted to identify patients with craniosynostosis born between 2008 and 2013. Data were verified using data provided by all hospitals that treated these patients. The following data were collected: date of birth, gender, diagnosis and postal code. Previously reported data from 1997 until 2007 were included to assess for change in prevalence over the years. Between 2008 and 2013 759 patients with craniosynostosis were born in the Netherlands. Prevalence of craniosynostosis was 7.2 per 10.000 live births. Sagittal synostosis was the most common form (44%). Poisson regression analysis showed a significant mean annual increase of prevalence of total craniosynostosis (+12.5%), sagittal (+11.7%) and metopic (+20.5%) synostosis from 1997 to 2013. The prevalence of craniosynostosis is 7.2 per 10.000 live born children in the Netherlands. Prevalence of total craniosynostosis, sagittal and metopic suture synostosis has risen significantly from 1997 until 2013, without obvious cause.

Journal of Cranio-Maxillofacial Surgery, 2016

An evaluation of our first 111 consecutive cases of non-syndromic endoscopically assisted cranios... more An evaluation of our first 111 consecutive cases of non-syndromic endoscopically assisted craniosynostosis surgery (EACS) followed by helmet therapy. Retrospective analysis of a prospective registration database was performed. Age, duration of surgery, length of hospital stay, blood loss, transfusion rate, cephalic index and duration of helmet therapy were evaluated. An online questionnaire was used to evaluate the burden of the helmet therapy for the child and parents. 111 EAC procedures were performed: 64 for scaphocephaly, 34 for trigonocephaly and13 for anterior plagiocephaly. The mean age at the time of surgery was 3.9 (±1) months, mean surgical time was 58 (±18) minutes, mean blood loss was 34 (±28) ml, transfusion rate was 22% (n = 26), mean duration of postoperative helmet therapy was 10 (±2.5) months, mean preoperative and postoperative CI were respectively 0.67(±0.057) and 0.72 (±0.062) in scaphocephalic patients and the mean length of hospital stay was 2.6 (±1) days. The burden of the helmet therapy for the child and his family was deemed very low. EACS for non-syndromic patients shows low morbidity rates, short surgical time, short length of hospital stay, little blood loss and low need for blood transfusion and is associated with satisfying cosmetic results.

Introduction: Today, no objective standardized planning procedure exists for the preoperative pla... more Introduction: Today, no objective standardized planning procedure exists for the preoperative planning of open cranial vault reconstruction of patients suffering from craniosynostosis. The use of a normative skull model, which will serve as a reference, will enhance the standardized planning procedure. Since no normative skull models of the Dutch population exist yet, a method was developed to create normative skull models of this population. Methods: Steps include the creation of volumetric data and threshold determination, creation of mesh data, registration, rendering and normalization. Results: A normative skull model represented as point cloud was created based on the CT scans of three patients. Conclusion: The presented method enables the creation of normative skull models, using three CT data sets containing skull images. Therefore, this method is suitable for the creation of normative skull models of the Dutch population.

Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the association of ... more Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the association of large and/or multiple congenital melanocytic nevi (CMN) of the skin with melanocytic lesions of the leptomeninges, including melanocytosis. Leptomeningeal melanocytosis carries a poor prognosis once neurological symptoms develop. Despite surgery, which is often not radical, few other treatment options exist. Recently, it was demonstrated that early embryonic, post-zygotic somatic mutations in the NRAS gene are implicated in the pathogenesis of NCM. In this report, we present a 13-year-old boy with NCM and progressive symptomatic leptomeningeal melanocytosis. A somatic NRAS Q61K mutation was present in both CMN as well as the melanocytosis. Despite repeated surgery, the patient showed clinical progression. Therefore, treatment with MEK162, a MEK inhibitor, was started on compassionate use base. The patient died only five days later, i.e. too early to expect a clinical effect of MEK162 therapy. We therefore studied the effect of MEK162 at the protein level in the leptomeningeal tumor by immunohistochemical and Western Blot analyses using Ki67 and pERK antibodies. We observed lower MIB-1 expression and lower pERK expression in the post-treatment samples compared to pre-treatment, suggesting a potential effect of MEK inhibiting therapy. Further studies are needed to determine whether MEK inhibitors can effectively target NRAS-mutated symptomatic NCM, a rare but potentially fatal disease.

International Journal of Oral and Maxillofacial Surgery, 2019

Insight into the growth and development of the normal newborn cranial shape is essential to monit... more Insight into the growth and development of the normal newborn cranial shape is essential to monitor cranial development, to detect and diagnose abnormal skull shapes, and for the long-term follow-up of craniosynostosis surgery. The aim of this study was to analyse the growth pattern of the cranial shape of infants during the first years of life using 3D stereophotogrammetry and 3D computed tomography (CT) with advanced 3D evaluation techniques. A large set of 3D photographs (n=199) and CT scans (n=183), taken between ages 0 and 54 months, was collected. Cranial shapes with artefacts and asymmetries were removed. Total volumes and intracranial volumes were obtained, as well as 3D and 2D measurements, including the cranial width, cranial length, cranial index, and suture lengths. Growth maps were created for all modalities to indicate 3D growth over time. For the final analysis, a total of 130 3D photographs, 94 hard tissue CT scans, and 76 soft tissue CT scans were used. 3D and 2D measures, volumes, growth maps, and growth animations were obtained. A non-uniform growth was revealed by the 3D growth maps. This study addresses the need for normative cranial evolution data to monitor healthy cranial development and for detection, follow-up, and treatment planning in craniosynostosis.

Acta Neurochirurgica, 2019

Background The surgeons’ estimate of the extent of resection (EOR) shows little accuracy in previ... more Background The surgeons’ estimate of the extent of resection (EOR) shows little accuracy in previous literature. Considering the developments in surgical techniques of glioblastoma (GBM) treatment, we hypothesize an improvement in this estimation. This study aims to compare the EOR estimated by the neurosurgeon with the EOR determined using volumetric analysis on the post-operative MR scan. Methods Pre- and post-operative tumor volumes were calculated through semi-automatic volumetric assessment by three observers. Interobserver agreement was measured using intraclass correlation coefficient (ICC). A univariate general linear model was used to study the factors influencing the accuracy of estimation of resection percentage. Results ICC was high for all three measurements: pre-operative tumor volume was 0.980 (0.969–0.987), post-operative tumor volume 0.974 (0.961–0.984), and EOR 0.947 (0.917–0.967). Estimation of EOR by the surgeon showed moderate accuracy and agreement. Multivariab...

Plastic and Reconstructive Surgery - Global Open, 2019

Plastic and Reconstructive Surgery - Global Open, 2019

Conclusion: Natural improvement was observed, which advocates reassessment in a selected group. S... more Conclusion: Natural improvement was observed, which advocates reassessment in a selected group. Short-term neurocognitive evaluation can be indicative for the future, but further longitudinal follow-up is necessary to determine whether there is a neurocognitive indication for operation or whether it is just an aesthetic procedure. This knowledge is important, in order to better involve parents in the shared decision making process of this possible high risk procedure.

Surgical Innovation, 2018

The implementation of augmented reality (AR) in image-guided surgery (IGS) can improve surgical i... more The implementation of augmented reality (AR) in image-guided surgery (IGS) can improve surgical interventions by presenting the image data directly on the patient at the correct position and in the actual orientation. This approach can resolve the switching focus problem, which occurs in conventional IGS systems when the surgeon has to look away from the operation field to consult the image data on a 2-dimensional screen. The Microsoft HoloLens, a head-mounted AR display, was combined with an optical navigation system to create an AR-based IGS system. Experiments were performed on a phantom model to determine the accuracy of the complete system and to evaluate the effect of adding AR. The results demonstrated a mean Euclidean distance of 2.3 mm with a maximum error of 3.5 mm for the complete system. Adding AR visualization to a conventional system increased the mean error by 1.6 mm. The introduction of AR in IGS was promising. The presented system provided a solution for the switchi...

Scientific reports, Jan 20, 2018

Virtual planning of open cranial vault reconstruction is used to simulate and define an pre-opera... more Virtual planning of open cranial vault reconstruction is used to simulate and define an pre-operative plan for craniosynostosis surgery. However, virtual planning techniques are subjective and dependent on the experience and preferences of the surgical team. To develop an objective automated 3D pre-operative planning technique for open cranial vault reconstructions, we used curvature maps for the shape comparison of the patient's skull with an age-specific reference skull. We created an average skull for the age-group of 11-14 months. Also, we created an artificial test object and selected a cranial CT-scan of an 11 months old trigonocephaly patient as test case. Mesh data of skulls were created using marching cubes and raycasting. Curvature maps were computed using quadric surface fitting. The shape comparison was tested for the test object and the average skull. Finally, shape comparison was performed for the trigonocephalic skull with the average skull. Similar shapes and the...

International journal of oral and maxillofacial surgery, Jan 6, 2017

Craniosynostosis is a congenital defect which can result in abnormal cranial morphology. Three di... more Craniosynostosis is a congenital defect which can result in abnormal cranial morphology. Three dimensional (3D) stereophotogrammetry is potentially an ideal technique for the evaluation of cranial morphology and diagnosis of craniosynostosis because it is fast and harmless. This study presents a new method for objective characterization of the morphological abnormalities of scaphocephaly and trigonocephaly patients using 3D photographs of patients and healthy controls. Sixty 3D photographs of healthy controls in the age range of 3-6 months were superimposed and scaled. Principal component analysis (PCA) was applied to find the mean cranial shape and the cranial shape variation in this normal population. 3D photographs of 20 scaphocephaly and 20 trigonocephaly patients were analysed by this PCA model to test whether cranial deformities of scaphocephaly and trigonocephaly patients could be objectively identified. PCA was used to find the mean cranial shape and the cranial shape variat...