A preliminary analysis of replicating the biomechanics of helmet therapy for sagittal craniosynostosis.

PURPOSE: The aim of this study was to investigate the biomechanics of endoscopically assisted strip craniectomy treatment for the management of sagittal craniosynostosis while undergoing three different durations of postoperative helmet therapy using a computational approach. METHODS: A previously developed 3D model of a 4-month-old sagittal craniosynostosis patient was used. The strip craniectomy incisions were replicated across the segmented parietal bones. Areas across the calvarial were selected and constrained to represent the helmet placement after surgery. Skull growth was modelled and three variations of helmet therapy were investigated, where the timings of helmet removal alternated between 2, 5, and 8 months after surgery. RESULTS: The predicted outcomes suggest that the prolonging of helmet placement has perhaps a beneficial impact on the postoperative long-term morphology of the skull. No considerable difference was found on the pattern of contact pressure at the interface of growing intracranial volume and the skull between the considered helmeting durations. CONCLUSION: Although the validation of these simulations could not be performed, these simulations showed that the duration of helmet therapy after endoscopically assisted strip craniectomy influenced the cephalic index at 36 months. Further studies require to validate these preliminary findings yet this study can lay the foundations for further studies to advance our fundamental understanding of mechanics of helmet therapy.

Establishing Standards of Care in Craniosynostosis: Results from a Survey of ERN CRANIO Member Institutions.

BACKGROUND: European Reference Networks (ERNs) are networks involving hospitals with particular expertise in rare conditions. ERN-CRANIO focuses on rare disorders of the skull and face including craniosynostosis. METHODS: We undertook a pilot study in the form of an electronic survey to understand current practice in craniosynostosis management across ERN-CRANIO, which at the time consisted of 29 member institutions across 11 countries. Most (19 of 29) units replied; however, some answered the survey only partially. RESULTS: The majority (87.5%) of units have specific management protocols. For single-suture cases, 8 of 15 units see >50 new cases per year, 4 of 15 see 21-50 cases, and 3 of 15 see fewer than 20 cases. Duration of follow-up ranges from age 10 years or less (3 of 6) to indefinite (2 of 6). A variety of surgical techniques are used. For sagittal synostosis, the endoscopic and helmet technique is the most common (5 of 14), and for metopic and unicoronal synostosis, preferred by 9 of 14 centers was the frontoorbital remodeling (bandeau) technique. For multisutural syndromic craniosynostosis, 2 of 16 centers see >20 new cases per year, 4 of 16 see 11-20 cases, 5 of 16 see 6-10 cases, and 4 of 16 see fewer than 5 cases. Most centers (12 of 15) either never discharge syndromic patients or follow until adulthood. Eleven of 14 units perform prophylactic vault expansion, while 3 of 14 wait for clinical indication. Nine of 13 units operate at 6-12 months. Again, a wide variety of techniques are used, most commonly frontal advancement (4 of 13) initially. CONCLUSIONS: This study provides a useful snapshot of current standards of care in craniosynostosis across the high-volume centers of the ERN. Going forward, these results can be used to direct more detailed analysis of current practice, which will then be useful for constructing a management guideline for patients presenting with both single-suture and multisutural craniosynostosis.

Realistic simulator for craniosynostosis endoscopic approach.

Craniosynostosis is a premature fusion of cranial sutures, and it requires surgery to decrease cranial pressure and remodel the affected areas. However, mastering these procedures requires years of supervised training. Several neurosurgical training simulators have been created to shorten the learning curve. Laboratory training is fundamental for acquiring familiarity with the necessary techniques and skills to properly handle instruments. This video presents a novel simulator for training on the endoscopic treatment for scaphocephaly and trigonocephaly, covering all aspects of the procedure, from patient positioning to performing osteotomies. The video can be found here: https://vimeo.com/512526147.

Combining deep learning with 3D stereophotogrammetry for craniosynostosis diagnosis.

Craniosynostosis is a condition in which cranial sutures fuse prematurely, causing problems in normal brain and skull growth in infants. To limit the extent of cosmetic and functional problems, swift diagnosis is needed. The goal of this study is to investigate if a deep learning algorithm is capable of correctly classifying the head shape of infants as either healthy controls, or as one of the following three craniosynostosis subtypes; scaphocephaly, trigonocephaly or anterior plagiocephaly. In order to acquire cranial shape data, 3D stereophotographs were made during routine pre-operative appointments of scaphocephaly (n = 76), trigonocephaly (n = 40) and anterior plagiocephaly (n = 27) patients. 3D Stereophotographs of healthy infants (n = 53) were made between the age of 3-6 months. The cranial shape data was sampled and a deep learning network was used to classify the cranial shape data as either: healthy control, scaphocephaly patient, trigonocephaly patient or anterior plagiocephaly patient. For the training and testing of the deep learning network, a stratified tenfold cross validation was used. During testing 195 out of 196 3D stereophotographs (99.5%) were correctly classified. This study shows that trained deep learning algorithms, based on 3D stereophotographs, can discriminate between craniosynostosis subtypes and healthy controls with high accuracy.

Accuracy of the neurosurgeons estimation of extent of resection in glioblastoma.

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. Multivariable analysis showed a statistically significant effect of operating neurosurgeon (p = 0.01), use of fluorescence (p < 0.001), and resection percentage (p < 0.001) on the accuracy of the EOR estimation. CONCLUSION: All measurements through semi-automatic volumetric analysis show a high interobserver agreement, suggesting this to be a reliable assessment of EOR. We found a moderate reliability of the surgeons' estimate of EOR. Therefore, (early) post-operative MRI scanning for evaluation of EOR remains paramount.

Bedside placement of ventricular access devices under local anaesthesia in neonates with posthaemorrhagic hydrocephalus: preliminary experience.

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 general anaesthesia in the NICU and cohort III (n = 13) treated from December 2013 to December 2017 under local anaesthesia on the NICU. RESULTS: The overall infection rate was 14%; the VAD revision rate was 22% and did not differ significantly between the cohorts. Procedures under local anaesthesia never required conversion to general anaesthesia and were well tolerated. After an average of 33 tapping days, 38% of the neonates received a permanent ventriculoperitoneal (VP) shunt. The permanent VP shunt rate was 9% with VAD placement under local anaesthesia and 52% when performed under general anaesthesia (p = 0.02). CONCLUSION: Bedside placement of VADs for PHVD under local anaesthesia in neonates is a low-risk, well-tolerated procedure that results in at least equal results to surgery performed under general anaesthesia and/or performed in an OR.

Toward Holographic-Guided Surgery.

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 switching focus problem and created a more intuitive guidance system. With a further reduction in the error and more research to optimize the visualization, many surgical applications could benefit from the advantages of AR guidance.

Evaluation of anesthesia in endoscopic strip craniectomy: A review of 121 patients.

OBJECTIVE: 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 CO2 . 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.

Cranial shape comparison for automated objective 3D craniosynostosis surgery planning.

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 area on the patient's skull that maximally corresponded in shape with the reference shape were correctly identified. This study showed that curvature maps allow the comparison of craniosynostosis skulls with age-appropriate average skulls and a first step towards an objective user-independent pre-operative planning technique for open cranial vault reconstructions is made.

Topical vancomycin reduces the cerebrospinal fluid shunt infection rate: A retrospective cohort study.

OBJECT: Despite many efforts at reduction, cerebrospinal fluid (CSF) shunt infections are a major cause of morbidity in shunt surgery, occurring in 5-15% of cases. To attempt to reduce the shunt infection rate at our institution, we added topical vancomycin (intrashunt and perishunt) to our existing shunt infection prevention protocol in 2012. METHODS: We performed a retrospective cohort study comparing all shunted patients in January 2010 to December 2011 without vancomycin (control group, 263 procedures) to all patients who underwent shunt surgery between April 2012 and December 2015 with vancomycin (intervention group, 499 procedures). RESULTS: The overall shunt infection rate significantly decreased from 6.8% (control group) to 3.0% (intervention group) (p = 0.023, absolute risk reduction 3.8%, relative risk reduction 56%). Multivariate logistic regression analysis confirmed that the addition of topical vancomycin showed that cases treated under a protocol of topical vancomycin were associated with a decreased shunt infection rate (odds ratio [OR] 0.49 95% CI 0.25-0.998; p = 0.049). Age < 1 year was associated with an increased risk of infection (OR) 4.41, 95% CI 2,10-9,26; p = 0.001). Time from surgery to infection was significantly prolonged in the intervention group (p = 0.001). CONCLUSION: Adding intraoperative vancomycin to a shunt infection prevention protocol significantly reduces CSF shunt infection rate.

Intraoperative and postoperative complications in the surgical treatment of craniosynostosis: minimally invasive versus open surgical procedures.

OBJECTIVE To compare minimally invasive endoscopic and open surgical procedures, to improve informed consent of parents, and to establish a baseline for further targeted improvement of surgical care, this study evaluated the complication rate and blood transfusion rate of craniosynostosis surgery in our department. METHODS A prospective complication registration database that contains a consecutive cohort of all pediatric neurosurgical procedures in the authors' neurosurgical department was used. All pediatric patients who underwent neurosurgical treatment for craniosynostosis between February 2004 and December 2014 were included. In total, 187 procedures were performed, of which 121 were endoscopically assisted minimally invasive procedures (65%). Ninety-three patients were diagnosed with scaphocephaly, 50 with trigonocephaly, 26 with plagiocephaly, 3 with brachycephaly, 9 with a craniosynostosis syndrome, and 6 patients were suffering from nonsyndromic multisutural craniosynostosis. RESULTS A total of 18 complications occurred in 187 procedures (9.6%, 95% CI 6.2-15), of which 5.3% (n = 10, 95% CI 2.9-10) occurred intraoperatively and 4.2% (n = 8, 95% CI 2.2-8.2) occurred postoperatively. In the open surgical procedure group, 9 complications occurred: 6 intraoperatively and 3 postoperatively. In the endoscopically assisted procedure group, 9 complications occurred: 4 intraoperatively and 5 postoperatively. Blood transfusion was needed in 100% (n = 66) of the open surgical procedures but in only 21% (n = 26, 95% CI 15-30) of the endoscopic procedures. One patient suffered a transfusion reaction, and 6 patients suffered infections, only one of which was a surgical site infection. A dural tear was the most common intraoperative complication that occurred (n = 8), but it never led to postoperative sequelae. Intraoperative bleeding from a sagittal sinus occurred in one patient with only minimal blood loss. There were no deaths, permanent morbidity, or neurological sequelae. CONCLUSIONS Complications during craniosynostosis surgery were relatively few and minor and were without permanent sequelae in open and in minimally invasive procedures. The blood transfusion rate was significantly reduced in endoscopic procedures compared with open procedures.

Endoscopic third ventriculostomy and repeat endoscopic third ventriculostomy in pediatric patients: the Dutch experience.

OBJECTIVE After 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. METHODS Retrospective 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. RESULTS The hazard ratio for re-ETV failure relative to ETV failure was 1.23 (95% CI 0.90-1.69; p = 0.20). At 6 months, the success rates for both ETV and re-ETV were 68%. ETVSS was significantly related to the chances of re-ETV success (τ = 0.37; 95% bias corrected and accelerated CI 0.21-0.52; p < 0.001). The c-statistic was 0.74 (95% CI 0.64-0.85). The presence of prepontine arachnoid membranes and use of an external ventricular drain (EVD) were negatively associated with treatment success, with ORs of 4.0 (95% CI 1.5-10.5) and 9.7 (95% CI 3.4-27.8), respectively. CONCLUSIONS Re-ETV seems to be as safe and effective as initial ETV. ETVSS adequately predicts the chance of successful re-ETV. The presence of prepontine arachnoid membranes and the use of EVD negatively influence the chance of success.

Radiation-free 3D head shape and volume evaluation after endoscopically assisted strip craniectomy followed by helmet therapy for trigonocephaly.

INTRODUCTION: Radiation-free 3D post-operative sequential follow-up in craniosynostosis is hindered by the lack of consistent markers restricting evaluation to subjective comparison. However, using the computed cranial focal point (CCFP), it is possible to perform correct sequential image superposition and objective evaluation. We used this technique for mean volume and shape change evaluation of the head utilizing 3D photos after endoscopically assisted trigonocephaly surgery. METHODS: We performed a mean head shape and volume evaluation on age grouped 3D photos (n = 86) of children who underwent endoscopically assisted strip craniectomy with helmet therapy. We used CT-scans of healthy children as reference. We performed a mean shape evolution analysis and calculated the anterior fossa to total volume ratio (A/T-ratio). The volume- and A/T-ratio pattern were compared with the reference group. RESULTS: The mean anterior fossa volume evolved from 336 ml (33.4% A/T-ratio) pre-surgery to 664 ml (36.0% A/T-ratio) at 37-48 months post-surgery. Both groups have a near similar volume- and A/T-ratio pattern over time. The first 18 months show a predominant growth around the resected metopic suture. Between 18 and 24 months we observed mostly anterior orbital rim growth. From 24 months till 36-48 months the head grows predominantly at the temporal area. The least outward growth was observed at the temporal bones. CONCLUSION: Using a novel technique we were able to objectively evaluate head shape and volume using stereophotogrammetry after endoscopically assisted strip craniectomy. The A/T-ratio and volume growth pattern of endoscopically treated patients is near identical to that of the normal reference group.

Increase of prevalence of craniosynostosis.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Endoscopically assisted craniosynostosis surgery (EACS): The craniofacial team Nijmegen experience.

INTRODUCTION: An evaluation of our first 111 consecutive cases of non-syndromic endoscopically assisted craniosynostosis surgery (EACS) followed by helmet therapy. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Intraoperative complications in pediatric neurosurgery: review of 1807 cases.

OBJECTIVE Minimal literature exists on the intraoperative complication rate of pediatric neurosurgical procedures with respect to both surgical and anesthesiological complications. The aim of this study, therefore, was to establish intraoperative complication rates to provide patients and parents with information on which to base their informed consent and to establish a baseline for further targeted improvement of pediatric neurosurgical care. METHODS A clinical complication registration database comprising a consecutive cohort of all pediatric neurosurgical procedures carried out in a general neurosurgical department from January 1, 2004, until July 1, 2012, was analyzed. During the study period, 1807 procedures were performed on patients below the age of 17 years. RESULTS Sixty-four intraoperative complications occurred in 62 patients (3.5% of procedures). Intraoperative mortality was 0.17% (n = 3). Seventy-eight percent of the complications (n = 50) were related to the neurosurgical procedures, whereas 22% (n = 14) were due to anesthesiology. The highest intraoperative complication rates were for cerebrovascular surgery (7.7%) and tumor surgery (7.4%). The most frequently occurring complications were cerebrovascular complications (33%). CONCLUSIONS Intraoperative complications are not exceptional during pediatric neurosurgical procedures. Awareness of these complications is the first step in preventing them.

Creating a normative database of age-specific 3D geometrical data, bone density, and bone thickness of the developing skull: a pilot study.

OBJECT: Finite element models (FEMs) of the head are used to study the biomechanics of traumatic brain injury and depend heavily on the use of accurate material properties and head geometry. Any FEM aimed at investigating traumatic head injury in children should therefore use age-specific dimensions of the head, as well as age-specific material properties of the different tissues. In this study, the authors built a database of age-corrected skull geometry, skull thickness, and bone density of the developing skull to aid in the development of an age-specific FEM of a child's head. Such a database, containing age-corrected normative skull geometry data, can also be used for preoperative surgical planning and postoperative long-term follow-up of craniosynostosis surgery results. METHODS: Computed tomography data were processed for 187 patients (age range 0-20 years old). A 3D surface model was calculated from segmented skull surfaces. Skull models, reference points, and sutures were processed into a MATLAB-supported database. This process included automatic calculation of 2D measurements as well as 3D measurements: length of the coronal suture, length of the lambdoid suture, and the 3D anterior-posterior length, defined as the sum of the metopic and sagittal suture. Skull thickness and skull bone density calculations were included. RESULTS: Cephalic length, cephalic width, intercoronal distance, lateral orbital distance, intertemporal distance, and 3D measurements were obtained, confirming the well-established general growth pattern of the skull. Skull thickness increases rapidly in the first year of life, slowing down during the second year of life, while skull density increases with a fast but steady pace during the first 3 years of life. Both skull thickness and density continue to increase up to adulthood. CONCLUSIONS: This is the first report of normative data on 2D and 3D measurements, skull bone thickness, and skull bone density for children aged 0-20 years. This database can help build an age-specific FEM of a child's head. It can also help to tailor preoperative virtual planning in craniosynostosis surgery toward patient-specific normative target values and to perform objective long-term follow-up in craniosynostosis surgery.

Experimental treatment of NRAS-mutated neurocutaneous melanocytosis with MEK162, a MEK-inhibitor.

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 NRASQ61K 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.

Prospective review of a single center's general pediatric neurosurgical intraoperative and postoperative complication rates.

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 to the operating room in relation to an AE happened in 10.5% of all procedures and in 52% of procedures associated with AEs, the majority of which were related to CSF disorders. CONCLUSIONS: The CR in pediatric neurosurgical procedures was significant, and more than half of the patients with an AE required a repeat surgical procedure. Analysis of CRs should be a prerequisite for the prevention of complications and for the development of targeted interventions to reduce the CR (for example, infection rates).