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Objective Stagnation of skull growth is correlated with papilledema in craniosynostosis. In this retrospective cohort study, we describe the postoperative skull growth after surgical correction for sagittal synostosis and its relation to the development of papilledema. Methods Patients with isolated sagittal synostosis at our center between 2005 and 2012 were included. Occipitofrontal circumference (OFC) was analyzed, at 3 time points (preoperative, 2 years postoperative, and last OFC measurement) and 3 phases (initial postoperative growth, long-term growth, and overall growth), and related to papilledema on fundoscopy. Results In total, 163 patients were included. The first time interval showed a decline in skull growth, with subsequent stabilization at long term. Papilledema occurred postoperatively in 10 patients. In these patients, the OFC at 2 years and at last follow-up (T3) were significantly smaller than in patients without papilledema. A larger OFC resulted in a decreased odds of developing papilledema at both postoperative time points (at T2 (OR = 0.40, p = 0.01) and at T3 (OR 0.29, p Conclusion A small OFC is correlated with the occurrence of papilledema. A decline in OFC within 2 years postoperatively is common in sagittal synostosis and is acceptable up to a value of 0.25SD. Patients with an OFC at last follow-up of less than 0.5SD are at risk for developing papilledema.

Introduction: Paediatric patients with disorders that involve brain functioning are particularly vulnerable with respect to including them in shared decision-making. Current tools are mostly paper or digital patient information. We lay the groundwork for improving engagement with a concept that we coined ‘the Self-Portrait’. The main goals were to identify (1) obstacles and (2) design parameters that enable patient participation. Methods: A research-through-design approach was utilized in nine patients with brain-related disorders (4–12 years), 15 parents and 15 medical professionals, involving contextual research (interviews and observations) within the paediatric hospital and patients' homes and codesign. Sensitizing materials and early instances of design solutions were deployed as catalysts for communication. Five rounds of enriched interviews and design reviews were thematically analysed to answer the research questions. Results: Obstacles to child involvement were related to children's level of understanding, the time and energy necessary for information processing and lack of perceived relevance of the information. Patients' engagement is supported by design features that extend the time frame of interaction beyond the consultation, transfer information interactively and give control and influence during the consultation. Conclusion: Obstacles were detected that complicate child engagement, which differ between stakeholders. Promising design features were identified that have the potential to play an important role in enabling active child involvement. These findings show that applying principles of human-centred design research and codesign can bring together patients, parents and medical professionals around a tool that provides a shared language and focus, which are prerequisites to increase child engagement. Patient or Public Contribution: Patients, parents and clinicians contributed as design informants during contextual research and design reviews. Clinicians provided feedback on the initial outcomes of thematic analysis. Two researchers assisted in consensus sessions during the thematic analysis.

Purpose To obtain pediatric normative reference values and determine whether optical coherence tomography (OCT) corresponds better with clinical signs of intracranial hypertension (ICH) compared to the traditional screening method fundoscopy in a large cohort of one type of single suture craniosynostosis. Methods Control subjects without optic nerve diseases and isolated sagittal synostosis patients aged 3–10 years who underwent fundoscopy and OCT were included in this prospective cohort study. Normative reference values were obtained through bootstrap analysis. Main outcome was the association between peripapillary total retinal thickness (TRT) and total retinal volume (TRV) and appearance on fundoscopy. Signs and symptoms suggestive of ICH, including skull growth arrest, fingerprinting, and headache, were scored. Results Sixty-four healthy controls and 93 isolated sagittal synostosis patients were included. Normative cut-off values for mean TRT are 504 μm and for mean TRV 3 and > 0.39 mm3. TRT was increased in 16 (17%) and TRV in 15 (16%) of 93 patients, compared to only 4 patients with papilledema on fundoscopy (4%). Both parameters were associated with papilledema on fundoscopy (OR = 16.7, p = 0.02, and OR = 18.2, p = 0.01). Skull growth arrest was significantly associated with abnormal OCT parameters (OR = 13.65, p Conclusions The established cut-off points can be applied to screen for ICH in pediatrics. The present study detected abnormalities with OCT more frequent than with fundoscopy, which were associated with skull growth arrest. Therefore, a combination of OCT, fundoscopy, and skull growth arrest can improve clinical decision-making in craniosynostosis.

Background: Children with trigonocephaly are at risk for neurodevelopmental disorders. The aim of this study is to investigate white matter properties of the frontal lobes in young, unoperated patients with metopic synostosis as compared to healthy controls using diffusion tension imaging (DTI). Methods: Preoperative DTI data sets of 46 patients with trigonocephaly with a median age of 0.49 (interquartile range: 0.38) years were compared with 21 controls with a median age of 1.44 (0.98) years. White matter metrics of the tracts in the frontal lobe were calculated using FMRIB Software Library (FSL). The mean value of tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were estimated for each subject and compared to healthy controls. By linear regression, FA and MD values per tract were assessed by trigonocephaly, sex, and age. Results: The mean FA and MD values in the frontal lobe tracts of untreated trigonocephaly patients, younger than 3 years, were not significantly different in comparison to controls, where age showed to be a significant associated factor. Conclusions: Microstructural parameters of white matter tracts of the frontal lobe of patients with trigonocephaly are comparable to those of controls aged 0-3 years.

Background: Craniofacial surgery is the standard treatment for children with moderate to severe trigonocephaly. The added value of surgery to release restriction of the frontal lobes is unproven, however. In this study, the authors aim to address the hypothesis that the frontal lobe perfusion is not restricted in trigonocephaly patients by investigating cerebral blood flow. Methods: Between 2018 and 2020, trigonocephaly patients for whom a surgical correction was considered underwent magnetic resonance imaging brain studies with arterial spin labeling to measure cerebral perfusion. The mean value of cerebral blood flow in the frontal lobe was calculated for each subject and compared to that of healthy controls. Results: Magnetic resonance imaging scans of 36 trigonocephaly patients (median age, 0.5 years; interquartile range, 0.3; 11 female patients) were included and compared to those of 16 controls (median age, 0.83 years; interquartile range, 0.56; 10 female patients). The mean cerebral blood flow values in the frontal lobe of the trigonocephaly patients (73.0 ml/100 g/min; SE, 2.97 ml/100 g/min) were not significantly different in comparison to control values (70.5 ml/100 g/min; SE, 4.45 ml/100 g/min; p = 0.65). The superior, middle, and inferior gyri of the frontal lobe showed no significant differences either. Conclusions: The authors' findings suggest that the frontal lobes of trigonocephaly patients aged less than 18 months have a normal cerebral blood flow before surgery. In addition to the very low prevalence of papilledema or impaired skull growth previously reported, this finding further supports the authors' hypothesis that craniofacial surgery for trigonocephaly is rarely indicated for signs of raised intracranial pressure or restricted perfusion for patients younger than 18 months. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Aim: To identify meaningful outcomes of children and their caregivers attending a paediatric brain centre. Method: We compiled a long list of outcomes of health and functioning of children with brain-related disorders such as cerebral palsy, spina bifida, (genetic) neurodevelopmental disorders, and acquired brain injury. We incorporated three perspectives: patients, health care professionals, and published outcome sets. An aggregated list was categorized using the International Classification of Functioning, Disability, and Health: Children and Youth version in a patient validation survey for children and parent-caregivers to prioritize outcomes. Outcomes were considered meaningful when ranked ‘very important’ by 70% or more of the participants. Results: We identified 104 outcomes from the three perspectives. After categorizing, 59 outcomes were included in the survey. Thirty-three surveys were completed by children (n = 4), caregivers (n = 24), and parent-caregivers together with their child (n = 5). Respondents prioritized 27 meaningful outcomes covering various aspects of health and functioning: emotional well-being, quality of life, mental and sensory functions, pain, physical health, and activities (communication, mobility, self-care, interpersonal relationships). Parent-caregiver concerns and environmental factors were newly identified outcomes. Interpretation: Children and parent-caregivers identified meaningful outcomes covering various aspects of health and functioning, including caregiver concerns and environmental factors. We propose including those in future outcome sets for children with neurodisability.

PURPOSE This study is the first to evaluate the prevalence of retinal thinning and the correlation with papilledema and visual acuity (VA) in a large population with craniosynostosis. DESIGN Prospective clinical cohort study. METHODS All and complex patients syndromic and complex with craniosynostosis who visited the only national referral center between 2018 and 2020 were included. Retinal layers were segmented using optical coherence tomography. Patients were seen by an ophthalmologist for VA assessment and fundoscopy. Multivariate regression models were developed to evaluate correlations between retinal thickness, papilledema and VA. RESULTS We included 127 patients. Retinal thinning was most prevalent in the peripapillary retinal nerve fiber layer (≤38%). A longer duration of papilledema in early childhood correlated with an increased peripapillary retinal nerve fiber layer and total retinal thickness optic nerve head later in life (+0.3 ± 0.2, P = .04 and +1.0 ± 1.0, P = .003); however, its thickness was not correlated with the VA (P = .20 and P = .53). Macular retinal thinning was associated with a worse VA (P = .01); however, it was not correlated with the duration of papilledema (P = .95). CONCLUSIONS Following a preventative treatment strategy for syndromic and complex craniosynostosis, the prevalence of retinal ONH thinning is low. Although the prevalence of peripapillary retinal nerve fiber layer thinning is considerable, its thickness is not correlated with VA. In contrast, macular thinning is correlated with worse VA scores and should, therefore, be evaluated during follow-up. Future studies should evaluate the (1) causative mechanism for macular thinning, (2) correlation between the time to surgery and macular thinning, and (3) results of reactive treatment strategies and compare those results to the current study.

Purpose: Cerebellar tonsillar herniation (TH) occurs frequently in syndromic craniosynostosis; however, the exact pathogenesis is unknown. This study evaluates the association between skull base deformities and TH in syndromic craniosynostosis. Methods: Retrospective study MRI study comparing syndromic craniosynostosis to controls. Measured parameters included clivus length, skull base angle, Boogard's angle, foramen magnum area, and cerebellar tonsillar position (TP). The association between skull base parameters and TP was evaluated with linear mixed models, correcting for age and risk factors for TH in craniosynostosis (hydrocephalus, intracranial hypertension, craniocerebral disproportion, and lambdoid synostosis). Results: Two hundred and eighty-two scans in 145 patients were included, and 146 scans in 146 controls. The clivus was smaller at birth, and its growth was retarded in all syndromes. The skull base angle was smaller at birth in Apert and Crouzon syndromes, and the evolution through time was normal. Boogard's angle was smaller at birth in Apert syndrome, and its evolution was disturbed in Apert and Saethre-Chotzen syndromes. The foramen magnum was smaller at birth in Crouzon and Saethre-Chotzen syndromes, and its growth was disturbed in Apert, Crouzon, and Saethre-Chotzen syndromes. TP was higher at birth in Apert syndrome, but lowered faster. In Crouzon syndrome, TP was lower at birth and throughout life. A smaller clivus and larger foramen magnum were associated with a lower TP in controls (p

Trapped or isolated fourth ventricle (TFV) is a rare but critical neurosurgical condition, mostly occurring in pediatric patients, caused by a blockage of the in- and outlets of the fourth ventricle. The purpose of this study is to review all available data on the treatment options of TFV and to compare their safety, efficacy, and durability. MEDLINE, Embase, and Google Scholar were searched from inception to September 13, 2022, for prospective or retrospective cohorts, case-control studies, case series or case reports, reporting detailing outcomes of TFV patients, treated with an endoscopic-, microsurgical-, shunt placement,- or hybrid approaches to TFV. All authors were contacted to provide individual patient data. Eighty-seven articles (314 patients) were included in the individual patient data meta-analysis (IPD) and 9 (151 patients) in the cohort meta-analysis. The IPD revealed that primary endoscopic (aOR 0.21; [95% CI 0.08–0.57]) and microsurgical interventions (aOR 0.21; [95% CI 0.05–0.82]) were associated with a significantly lower revision rate, compared to shunt placement, when adjusted for confounders. Endoscopy was also associated with a significantly higher rate of clinical improvement (aOR 4.56; [95% CI 1.2–18]). The meta-analysis revealed no significant difference in revision rate between the endoscopic (0.33 [95% CI 0.0–0.52]) and shunt group (0.44 [95% CI 0.0–1.0]). Endoscopy should be considered as the first-line treatment of TFV due to its superior efficacy, durability, and similar safety, compared to shunt placement and its minimally invasive nature. Microsurgery should be considered as a second treatment option, due to its similar clinical outcomes and revision rate as endoscopy, but it is more invasive in nature.

OBJECTIVE Crouzon syndrome with acanthosis nigricans (CAN) is a rare and clinically complex subtype of Crouzon syndrome. At three craniofacial centers, this multicenter study was undertaken to assess clinical signs in relation to the required interventions and treatment course in patients with CAN. METHODS A retrospective cohort study of CAN was performed to obtain information about the clinical treatment course of these patients. Three centers participated: Erasmus Medical Centre, Rotterdam, the Netherlands; John Radcliffe Hospital, Oxford, United Kingdom; and Hôpital Necker-Enfants Malades, Paris, France. RESULTS Nineteen patients (5 males, 14 females) were included in the study. All children were operated on, with a mean of 2.2 surgeries per patient (range 1–6). Overall, the following procedures were performed: 23 vault expansions, 10 monobloc corrections, 6 midface surgeries, 11 foramen magnum decompressions, 29 CSF-diverting surgeries, 23 shunt-related interventions, and 6 endoscopic third ventriculostomies, 3 of which subsequently required a shunt. CONCLUSIONS This study demonstrates that patients with the mutation c.1172C>A (p.Ala391Glu) in the FGFR3 gene have a severe disease trajectory, requiring multiple surgical procedures. The timing and order of interventions have changed among patients and centers. It was not possible to differentiate the effect of a more severe clinical presentation from the effect of treatment order on outcome.

Three-dimensional (3D) stereophotogrammetry is a novel imaging technique that has gained popularity in the medical field as a reliable, non-invasive, and radiation-free imaging modality. It uses optical sensors to acquire multiple 2D images from different angles which are reconstructed into a 3D digital model of the subject's surface. The technique proved to be especially useful in craniofacial applications, where it serves as a tool to overcome the limitations imposed by conventional imaging modalities and subjective evaluation methods. The capability to acquire high-dimensional data in a quick and safe manner and archive them for retrospective longitudinal analyses, provides the field with a methodology to increase the understanding of the morphological development of the cranium, its growth patterns and the effect of different treatments over time.This review describes the role of 3D stereophotogrammetry in the evaluation of craniosynostosis, including reliability studies, current and potential clinical use cases, and practical challenges. Finally, developments within the research field are analyzed by means of bibliometric networks, depicting prominent research topics, authors, and institutions, to stimulate new ideas and collaborations in the field of craniofacial 3D stereophotogrammetry.We anticipate that utilization of this modality's full potential requires a global effort in terms of collaborations, data sharing, standardization, and harmonization. Such developments can facilitate larger studies and novel deep learning methods that can aid in reaching an objective consensus regarding the most effective treatments for patients with craniosynostosis and other craniofacial anomalies, and to increase our understanding of these complex dysmorphologies and associated phenotypes.

Aim: To assess the long-term outcomes of our management protocol for Saethre–Chotzen syndrome, which includes one-stage fronto-orbital advancement. Method: All patients born with Saethre–Chotzen syndrome between January 1992 and March 2017 were included. Evaluated parameters included occipital frontal head circumference (OFC), fundoscopy, neuroimaging (ventricular size, tonsillar position, and the presence of collaterals/an abnormal transverse sinus), polysomnography, and ophthalmological outcomes. The relationship between papilledema and its associated risk factors was evaluated with Fisher’s exact test. Results: Thirty-two patients (21 females, 11 males) were included. Median (SD) age at first surgery was 9.6 months (3.1mo) for patients who were primarily referred to our center (range: 3.6–13.0mo), the median (SD) age at last follow-up was 13 years (5y 7mo; range: 3–25y). Seven patients had papilledema preoperatively, which recurred in two. Two patients had papilledema solely after first surgery. Second cranial vault expansion was indicated in 20%. Thirteen patients had an OFC deflection, indicating restricted skull growth, one patient had ventriculomegaly, and none developed hydrocephalus. Eleven patients had emissary veins, while the transverse sinus was aberrant unilaterally in 13 (hypoplastic n=10 and absent n=3). Four patients had mild tonsillar descent, one of which was a Chiari type I malformation. Four patients had obstructive sleep apnoea (two mild, one moderate, and one severe). An aberrant transverse sinus was associated with papilledema (p=0.01). Interpretation: Single one-stage fronto-orbital advancement was sufficient to prevent intracranial hypertension for 80% of our patients with Saethre–Chotzen syndrome. Follow-up should focus on OFC deflection and venous anomalies.

OBJECTIVEIn comparison with the general population, children with syndromic craniosynostosis (sCS) have abnormal cerebral venous anatomy and are more likely to develop intracranial hypertension. To date, little is known about the postnatal development change in cerebral blood flow (CBF) in sCS. The aim of this study was to determine CBF in patients with sCS, and compare findings with control subjects.METHODSA prospective cohort study of patients with sCS using MRI and arterial spin labeling (ASL) determined regional CBF patterns in comparison with a convenience sample of control subjects with identical MRI/ASL assessments in whom the imaging showed no cerebral/neurological pathology. Patients with SCS and control subjects were stratified into four age categories and compared using CBF measurements from four brain lobes, the cerebellum, supratentorial cortex, and white matter. In a subgroup of patients with sCS the authors also compared longitudinal pre- to postoperative CBF changes.RESULTSSeventy-six patients with sCS (35 female [46.1%] and 41 male [53.9%]), with a mean age of 4.5 years (range 0.2–19.2 years), were compared with 86 control subjects (38 female [44.2%] and 48 male [55.8%]), with a mean age of 6.4 years (range 0.1–17.8 years). Untreated sCS patients < 1 year old had lower CBF than control subjects. In older age categories, CBF normalized to values observed in controls. Graphical analyses of CBF by age showed that the normally expected peak in CBF during childhood, noted at 4 years of age in control subjects, occurred at 5–6 years of age in patients with sCS. Patients with longitudinal pre- to postoperative CBF measurements showed significant increases in CBF after surgery.CONCLUSIONSUntreated patients with sCS < 1 year old have lower CBF than control subjects. Following vault expansion, and with age, CBF in these patients normalizes to that of control subjects, but the usual physiological peak in CBF in childhood occurs later than expected.

OBJECTIVE Ten years ago, the authors reported on the outcome of their study investigating the degree of discomfort and pain in newborns with myelomeningocele (MMC), using the parameters of unbearable and hopeless suffering. In the current study, they investigated the quality of life, daily functioning, pain and fatigue, ability to communicate, and number of surgeries in the same cohort of patients. They subdivided their study population into severe (Lorber) and less severe (non-Lorber) cases and compared these cases with a healthy population (non-MMC group) and with each other. METHODS The parents of 22 of 28 patients gave informed consent for this study. The KIDSCREEN-27 and PEDI-CAT (Pediatric Evaluation of Disability Inventory) were used to assess quality of life and daily functioning. Pain and fatigue were self-reported on a 10-point numeric rating scale. Communication and ambulation levels were determined using the Communication Function Classification System (CFCS) and the Hoffer ambulation scale. Using reference data from the KIDSCREEN-27 and PEDI-CAT, the authors created a healthy population comparison group. RESULTS There was no significant difference in health-related quality-of-life (HRQOL) scores between Lorber and non-Lorber patients, except that school environment domain scores were lower in the Lorber group. When comparing the HRQOL of MMC patients with that of the non-MMC group, the physical well-being and parent relations and autonomy domains scored significantly lower. The daily functioning of MMC patients was lower on all domains of the PEDI-CAT compared with the non-MMC group. Lorber MMC patients scored lower on all domains of the PEDI-CAT when compared with non-Lorber patients. All patients were capable of communicating effectively; most patients (n = 18) were considered CFCS level I, and 4 patients were considered CFCS level II. CONCLUSIONS This study shows that MMC is a severe, lifelong condition that affects patients’ lives in many domains. All the patients in this study are capable of effective communication, irrespective of severity of MMC. Overall, the data show that in newborn MMC patients, future unbearable suffering with respect to pain, mobility, cognition, and communication is hard to predict and may not always occur.

A 35-year-old male with Saethre-Chotzen syndrome presented with severe complaints. Neuroimaging showed a Chiari-I malformation, mild ventriculomegaly, a syrinx of the wide central canal, and various cerebral vascular anomalies including a large occipital emissary vein on the right. Ultrasound of this vein confirmed blocking of the outflow-track when turning his head to the right, which also provoked the headaches and bruit. Polysomnography revealed severe positional sleep apnea with a mixed breathing pattern, the central components consisted of periodic breathing with, at times, crescendo-decrescendo reminiscent of a Cheyne-Stokes versus Biot breathing pattern, pointing to possible brain stem/pontine problems. Continuous positive airway pressure was initiated, and the patient was instructed to avoid sleeping in the right lateral position. One year later, nearly all his complaints have resolved. A questionnaire was sent to all adult Saethre-Chotzen patients in our craniofacial unit, none reported any of the severe symptoms as described by our index case.

Stagnation of skull growth is correlated with papilledema in craniosynostosis. In this retrospective cohort study, we describe the postoperative skull growth after surgical correction for sagittal synostosis and its relation to the development of papilledema.Patients with isolated sagittal synostosis at our center between 2005 and 2012 were included. Occipitofrontal circumference (OFC) was analyzed, at 3 time points (preoperative, 2 years postoperative, and last OFC measurement) and 3 phases (initial postoperative growth, long-term growth, and overall growth), and related to papilledema on fundoscopy.In total, 163 patients were included. The first time interval showed a decline in skull growth, with subsequent stabilization at long term. Papilledema occurred postoperatively in 10 patients. In these patients, the OFC at 2 years and at last follow-up (T3) were significantly smaller than in patients without papilledema. A larger OFC resulted in a decreased odds of developing papilledema at both postoperative time points (at T2 (OR = 0.40, p = 0.01) and at T3 (OR 0.29, p 0.001)). Sensitivity and specificity analysis indicated that an OFC below 0.25 SD at T2 (sensitivity 90%, specificity 65%) and below 0.49 at T3 (sensitivity 100%, specificity 60%) are related to the occurrence of papilledema.A small OFC is correlated with the occurrence of papilledema. A decline in OFC within 2 years postoperatively is common in sagittal synostosis and is acceptable up to a value of 0.25SD. Patients with an OFC at last follow-up of less than 0.5SD are at risk for developing papilledema.

To evaluate the impact of risk factors for intracranial hypertension (ICH) on cerebral cortex thickness in syndromic craniosynostosis.ICH risk factors including papilloedema, hydrocephalus, obstructive sleep apnea (OSA), cerebellar tonsillar position, occipitofrontal circumference (OFC) curve deflection, age, and sex were collected from the records of patients with syndromic craniosynostosis (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen syndromes) and imaging. Magnetic resonance images were analysed and exported for statistical analysis. A linear mixed model was developed to determine correlations with cerebral cortex thickness changes.In total, 171 scans from 107 patients (83 males, 88 females [including repeated scans], mean age 8y 10mo, range 1y 1mo-34y, SD 5y 9mo) were evaluated. Mean cortical thickness in this cohort was 2.78mm (SD 0.17). Previous findings of papilloedema (p=0.036) and of hydrocephalus (p=0.007) were independently associated with cortical thinning. Cortical thickness did not vary significantly by sex (p=0.534), syndrome (p=0.896), OSA (p=0.464), OFC (p=0.375), or tonsillar position (p=0.682).Detection of papilloedema or hydrocephalus in syndromic craniosynostosis is associated with significant changes in cortical thickness, supporting the need for preventative rather than reactive treatment strategies.Papilloedema is associated with thinning of the cerebral cortex in syndromic craniosynostosis, independently of hydrocephalus.Hipertensión intracraneal y grosor cortical en craneosinostosis sindrómica OBJETIVO: Evaluar el impacto de los factores de riesgo de hipertensión intracraneal (HIC) en el grosor de la corteza cerebral en la craneosinostosis sindrómica. MÉTODO: La neuroimagen, y, los factores de riesgo para HIC que incluyeron papiledema, hidrocefalia, apnea obstructiva del sueño (SAOS), posición de la tonsila cerebelosa, edad de desviación de la curva de circunferencia occipitofrontal (CFO) y el sexo, se recogieron de los registros de pacientes con craneosinostosis sindrómica (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzensis). Las imágenes de resonancia magnética fueron analizadas y exportadas para análisis estadístico. Se desarrolló un modelo mixto lineal para determinar las correlaciones con los cambios en el espesor de la corteza cerebral. RESULTADOS: En total se evaluaron 171 exploraciones de 107 pacientes (83 varones, 88 mujeres [incluyendo escaneos repetidos], edad media 8 años 10 meses, rango 1 año 1 mes - 34 años, DE 5 años 9 meses). El espesor medio cortical en esta cohorte fue de 2,78 mm (DS 0,17). Los hallazgos anteriores de papiledema (p=0,036) y de hidrocefalia (p=0,007) se asociaron de forma independiente con el adelgazamiento cortical. El grosor cortical no varió significativamente por sexo (p=0,534), síndrome (p=0,896), SAOS (p=0,464), CFO (p=0,375), o posición tonsilar (p=0,682). INTERPRETACIÓN: La detección de papiledema o hidrocefalia en la craneosinostosis sindrómica, se asocia con cambios significativos en el grosor cortical. Esto apoya la necesidad de estrategias de tratamiento preventivo en lugar de tratamientos reactivos.Hipertensão intracrianiana e espessura cortical na craniossinostose sindrômica OBJETIVO: Avaliar o impacto de fatores de risco para hipertensão intracraniana (HIC) na espessura cortical em craniossinostose sindrômica. MÉTODO: Fatores de risco para HIC incluindo papiloedema, hidrocefalia, apnéia obstrutiva do sono (AOS), posição das tonsilas do cerebelo, idade de deflexão da curva da circunferência occipitofrontal (COF), e sexo foram coletados dos registros de pacientes com craniossinostose sindrômica (síndromes de Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen) e imagens. As imagens de ressonância magnética foram analisadas e exportadas para análise estatística. Um modelo linear misto foi desenvolvido para determinar correlações com mudanças na espessura do córtex cerebral. RESULTADOS: No total, 171 imagens de 107 pacientes (83 do sexo masculino, 88 do sexo feminino [incluindo varreduras repetidas], média de idade 8a 10m, variação 1a 1m-34a, DP 5a 9m) foram avaliados. A espessura cortical média nesta coorte foi 2,78mm (DP 0,17). Achados prévios de papiloedema (p=0,036) e de hidrocefalia (p=0,007) foram independentemente associados com a redução cortical. A espessura cortical não variou significativamente com o sexo (p=0,534), síndrome (p=0,896), AOS (p=0,464), COF (p=0,375), ou posição tonsilar (p=0,682). INTERPRETAÇÃO: A detecção do papiloedema ou hidrocefalia na craniossinostose sindrômica se associa com mudanças significativas na espessura cortical, sustentando a necessidade de estratégias de tratamento preventivas e não reativas.

The prognosis of diffuse intrinsic pontine glioma (DIPG) is poor. The role of biopsy in DIPG remains controversial since the diagnosis may be established with imaging alone. Recent advances in understanding molecular biology and targeting of brain tumors have created a renewed interest in biopsy for DIPG. The Neurosurgery Working Group (NWG) of the SIOP-Europe Brain Tumor Group (BTG) undertook a survey among international pediatric neurosurgeons to define their current perceptions and practice regarding DIPG biopsy. The NWG developed a 20-question survey which was emailed to neurosurgeons in the International Society for Pediatric Neurosurgery (ISPN). The questionnaire included questions on diagnosis, indications, and techniques for biopsy, clinical trials, and healthcare infrastructure. The survey was sent to 202 neurosurgeons and 73 (36%) responded. Consensus of > 75% agreement was reached for 12/20 questions, which included (1) radiological diagnosis of DIPG is sufficient outside a trial, (2) clinical trial–based DIPG biopsy is justified if molecular targets are investigated and may be used for treatment, and (3) morbidity/mortality data must be collected to define the risk:benefit ratio. The remaining 8/20 questions proved controversial and failed to reach consensus. Routine DIPG biopsy continues to be debated. Most neurosurgeons agreed that DIPG biopsy within a clinical trial should be supported, with the aims of defining the procedure risks, improving understanding of tumor biology, and evaluating new treatment targets. Careful family counseling and consent remain important.

OBJECTIVEIntracranial hypertension is a major concern in children with syndromic craniosynostosis (sCS). Cerebral venous hypertension caused by cerebral venous outflow obstruction is believed to contribute to intracranial hypertension. The authors therefore hypothesized that cerebral venous volume would be increased in those children with sCS and intracranial hypertension.METHODSIn a case series of 105 children with sCS, of whom 32 had intracranial hypertension, cerebral MRI techniques were used to quantify the volume of the superior sagittal sinus, straight sinus (StrS), and both transverse sinuses.RESULTSLinear regression showed that total cerebral venous volume increased by 580.8 mm3 per cm increase in occipitofrontal head circumference (p < 0.001). No significant difference was found between the intracranial hypertension group and the nonintracranial hypertension group (p = 0.470). Multivariate ANOVA showed increased StrS volume (as a proportion of total volume) in the intracranial hypertension group (8.5% vs 5.1% in the nonintracranial hypertension group, p < 0.001). Multivariate logistic regression showed that a 100-mm3 increase in StrS volume is associated with increased odds of having intracranial hypertension by 60% (OR 1.60, 95% CI 1.24–2.08).CONCLUSIONSAlthough intracranial hypertension was not associated with total cerebral venous volume increase, it was associated with an isolated increase in StrS volume. Hence, it is unlikely that general cerebral venous outflow obstruction is the mechanism of intracranial hypertension in sCS. Rather, these findings indicate either a central cerebral vulnerability to intracranial hypertension or a mechanism involving venous blood redistribution.

Aim: To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis. Method: Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo–24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls). MRIs were processed via FreeSurfer pipeline to determine total ICV and cortical surface area (CSA). Scaling coefficients were calculated from log-transformed data via mixed regression to account for multiple measurements, sex, syndrome, and age. Educational outcomes were reported by syndrome. Results: Mean ICV was greater in patients with FGFR (1519cm3, SD 269cm3, p=0.016) than in patients with TWIST1 (1304cm3, SD 145cm3) or controls (1405cm3, SD 158cm3). CSA was related to ICV by a scaling law with an exponent of 0.68 (95% confidence interval [CI] 0.61–0.76) in patients with FGFR compared to 0.81 (95% CI 0.50–1.12) in patients with TWIST1 and 0.77 (95% CI 0.61–0.93) in controls. Lobar analysis revealed reduced scaling in the parietal (0.50, 95% CI 0.42–0.59) and occipital (0.67, 95% CI 0.54–0.80) lobes of patients with FGFR compared with controls. Modified learning environments were needed more often in patients with FGFR. Interpretation: Despite adequate ICV in FGFR-mediated craniosynostosis, CSA development is reduced, indicating maldevelopment, particularly in parietal and occipital lobes. Modified education is also more common in patients with FGFR.

Summary Background The aim of this study is to identify if certain types of craniosynostosis and/or surgical procedures are more likely to require a secondary intracranial procedure because of insufficient correction of skull shape or raised ICP after initial surgery. Methods All consecutive cases with craniosynostosis that were operated at our center between January 2010 and January 2019 were included and the number of secondary operations of the vault were determined, as well as diagnosis, the indication and type and timing of initial surgery. Monobloc and facial bipartition procedures were excluded. Results Over a nine year period, 790 vault corrections were performed in 780 patients of which 38 procedures were reoperations in 35 patient because of raised intracranial pressure or an insufficient esthetic result of the skull shape. Particularly patients with a multisutural or syndromic craniosynostosis are represented in this group, as well as three surgical procedures: 1. biparietal outfracturing for sagittal synostosis; 2. endoscopic stripcraniectomy with helmet therapy for unicoronal, multisutural or syndromic craniosynostosis; 3. conventional occipital expansion for syndromic craniosynostosis. Conclusions The risk of a second intracranial correction for insufficient outcome of skull shape or for raised ICP is related to type of synostosis and type of initial surgical technique. Particularly multisutural and syndromic craniosynostosis are more likely to require repeat surgery for these indications. Concerning initial technique, biparietal outfracturing does not correct sagittal synostosis sufficiently, stripcraniectomy with helmet therapy appears to undercorrect unicoronal, multisutural and syndromic synostosis, and conventional occipital expansion for multisutural and syndromic synostosis has poorer outcome than occipital expansion with distraction.

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0-86.5), 61.9% (51.6-74.2), 80.0% (95% CI 51.6-100.0), and 44.9% (95% CI 28.6-70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1-7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3-9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1-4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1-6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1-0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed.

BACKGROUND: This series describes the results of minimally invasive strip craniotomy with additional spring distraction.METHODS: Included are the first 83 consecutive patients who underwent this procedure (January 1, 2010, to January 1, 2014). Outcome parameters were collected prospectively and included surgical parameters and complications, the occurrence of papilledema, skull growth, cephalic index, and photographic scores.RESULTS: Duration of surgery was 63 minutes, 19 percent required blood transfusion, and complications were minor. Postoperative papilledema occurred in two patients (2.4 percent). Head growth increased after insertion of the springs and declined afterward to 0.7 SD, comparable to earlier cohorts in the authors' center. The cephalic index increased from 67 before surgery to 74 after surgery and showed a small decrease during the 4-year follow-up. Photographic scores confirmed the initial improvement and showed a trend to further improvement during follow-up.CONCLUSIONS: In this cohort, spring-assisted, minimally invasive strip craniotomy was safe and effective. Results were similar to those from other techniques but with smaller incisions, shorter interventions, reduced blood loss, and a lower incidence of postoperative papilledema.CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Introduction: Posterior distraction is the preferred surgical treatment for particularly Apert and Crouzon syndrome in most craniofacial centers, using either external distractors or springs. The authors prefer the use of springs and have adapted their technique to further improve outcomes. Methods: All patients who were treated with the adapted technique for occipital expansion using springs were included. The most significant adaption that the authors introduced in 2017 is using a bony hinge at the top of the vault instead of at the caudal edge of the occiput. Results: A total of 8 posterior expansions with springs were performed. No complications occurred and the springs were also successfully applied in cases with extremely thin bone. If indicated, a simultaneous foramen magnum decompression was performed and this was easier to combine with a hinge at the top of the vault. Conclusions: Posterior distraction with springs is a safe and effective procedure and allows a simultaneous foramen magnum decompression. Planning the hinge at the vault allows intracranial volume gain at the site of the posterior skull base.

Tumors of pineal cell origin are rare intracranial lesions. They are the second most common entity encountered in the pineal gland, after tumors of germ cell origin. They are classified according to their differentiation in pineocytomas (World Health Organization [WHO] grade I tumor), pineal parenchymal tumors of intermediate differentiation, papillary tumors of the pineal region, and pineoblastomas (WHO grade 4 tumor). Differentiation between pineal and germ cell tumors is essential, and for this purpose serum and cerebrospinal fluid (CSF) markers are used, alongside imaging techniques. Often, the only way to differentiate these two types of tumors is through a biopsy, which may be carried out with or without a simultaneous third ventriculocisternostomy. Retrospective series show an association between the extent of resection and improved outcomes, and benign lesions may be cured by performing a gross total resection. However, the approaches to this region are highly complex, because of the plethora of essential neuroanatomical structures in the area. The approaches need to be tailored to the specific anatomy of the patient and should aim at minimizing surgical morbidity. Because of their complexity, these lesions should mainly be performed in centers with sufficient experience in the treatment of pineal region lesions.

Background: Episodes of intracranial hypertension are associated with reductions in cerebral cortical thickness (CT) in syndromic craniosynostosis. Here we focus on Crouzon–Pfeiffer syndrome patients to measure CT and evaluate associations with type of primary cranial vault expansion and synostosis pattern. Methods: Records from 34 Crouzon–Pfeiffer patients were reviewed along with MRI data on CT and intracranial volume to examine associations. Patients were grouped according to initial cranial vault expansion (frontal/occipital). Data were analyzed by multiple linear regression controlled for age and brain volume to determine an association between global/lobar CT and vault expansion type. Synostosis pattern effect sizes on global/lobar CT were calculated as secondary outcomes. Results: Occipital expansion patients demonstrated 0.02mm thicker cortex globally (P = 0.81) with regional findings, including: thicker cortex in frontal (0.02mm, P = 0.77), parietal (0.06mm, P = 0.44) and occipital (0.04mm, P = 0.54) regions; and thinner cortex in temporal (−0.03mm, P = 0.69), cingulate (−0.04mm, P = 0.785), and, insula (−0.09mm, P = 0.51) regions. Greatest effect sizes were observed between left lambdoid synostosis and the right cingulate (d = −1.00) and right lambdoid synostosis and the left cingulate (d = −1.23). Left and right coronal synostosis yielded effect sizes of d = −0.56 and d = −0.42 on respective frontal lobes. Conclusions: Both frontal and occipital primary cranial vault expansions correlate to similar regional CT in Crouzon–Pfeiffer patients. Lambdoid synostosis appears to be associated with cortical thinning, particularly in the cingulate gyri. (Plast Reconstr Surg Glob Open 2020;8:e3204; doi: 10.1097/GOX.0000000000003204; Published online 4 November 2020.)

OBJECTIVEThe authors evaluated the long-term outcome of their treatment protocol for Muenke syndrome, which includes a single craniofacial procedure.METHODSThis was a prospective observational cohort study of Muenke syndrome patients who underwent surgery for craniosynostosis within the first year of life. Symptoms and determinants of intracranial hypertension were evaluated by longitudinal monitoring of the presence of papilledema (fundoscopy), obstructive sleep apnea (OSA; with polysomnography), cerebellar tonsillar herniation (MRI studies), ventricular size (MRI and CT studies), and skull growth (occipital frontal head circumference [OFC]). Other evaluated factors included hearing, speech, and ophthalmological outcomes.RESULTSThe study included 38 patients; 36 patients underwent fronto-supraorbital advancement. The median age at last follow-up was 13.2 years (range 1.3–24.4 years). Three patients had papilledema, which was related to ophthalmological disorders in 2 patients. Three patients had mild OSA. Three patients had a Chiari I malformation, and tonsillar descent < 5 mm was present in 6 patients. Tonsillar position was unrelated to papilledema, ventricular size, or restricted skull growth. Ten patients had ventriculomegaly, and the OFC growth curve deflected in 3 patients. Twenty-two patients had hearing loss. Refraction anomalies were diagnosed in 14/15 patients measured at ≥ 8 years of age.CONCLUSIONSPatients with Muenke syndrome treated with a single fronto-supraorbital advancement in their first year of life rarely develop signs of intracranial hypertension, in accordance with the very low prevalence of its causative factors (OSA, hydrocephalus, and restricted skull growth). This illustrates that there is no need for a routine second craniofacial procedure. Patient follow-up should focus on visual assessment and speech and hearing outcomes.

This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the early development of the skull, when one or more of the sutures close too early, causing problems with normal brain and skull growth. Research in this field has developed from early clinical case descriptions, to genetic discoveries responsible for the occurring malformations and onwards to developing sophisticated surgical treatment. In this article we describe these developments, zoom in on publication trends and characteristics and visualize developing networks and topic shifts in this research field.

The aim of this study was to report on a single center’s experience with spring-assisted cranial vault expansion (SAE) in patients with Crouzon syndrome and sagittal suture synostosis. Strip craniotomy with SAE has resulted in successful outcomes with low complication and revision rates in patients with isolated scaphocephaly. However, recent experience suggests that outcomes in patients with Crouzon syndrome and sagittal synostosis (SS) who undergo SAE are less favorable compared with the outcomes of those who undergo frontobiparietal (FBP) expansion. The authors reviewed both operations performed at a single center and noticed an upward expansion of the skull, which may be related to ventriculomegaly, with concurrent intracranial hypertension and poor aesthetic outcome. All patients diagnosed with Crouzon syndrome and SS who were treated with SAE required a revision FBP operation. Based on this outcome, the authors consider Crouzon syndrome a contraindication for correcting SS with springs.

OBJECTIVEPostoperative cerebellar mutism syndrome (pCMS) occurs in 7%–50% of children after cerebellar tumor surgery. Typical features include a latent onset of 1–2 days after surgery, transient mutism, emotional lability, and a wide variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome usually persist long term. The principal causal factor is bilateral surgical damage (regardless of tumor location) to any component of the proximal efferent cerebellar pathway, which leads to temporary dysfunction of cerebral cortical regions as a result of diaschisis. Tumor type, cerebellar midline location, and brainstem involvement are risk factors for pCMS that have been identified repeatedly, but they do not explain its latent onset. Ambiguous or negative results for other factors, such as hydrocephalus, postoperative meningitis, length of vermian incision, and tumor size, have been reached. The aim of this study was to identify perioperative clinical, radiological, and laboratory factors that also increase risk for the development of pCMS. The focus was on factors that might explain the delayed onset of pCMS and thus might provide a time window for taking precautionary measures to prevent pCMS or reduce its severity. The study was focused specifically on children who had undergone surgery for medulloblastoma.METHODSIn this single-center retrospective cohort study, the authors included 71 children with medulloblastoma, 28 of whom developed pCMS after primary resection. Clinical and laboratory data were collected prospectively and analyzed systematically. Variables were included for univariate and multivariate analysis.RESULTSUnivariate regression analysis revealed 7 variables that had a significant influence on pCMS onset, namely, tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and hematocrit (p = 0.003) in the pCMS group after surgery than in the no-pCMS group, significantly more reported incidents of severe bleeding in the tumor bed during surgery in the pCMS group, preoperative hydrocephalus, and a mean body temperature rise of 0.5°C in the first 4 days after surgery in the pCMS group. Multiple regression analysis revealed that tumor size, tumor infiltration into or compression of the brainstem, and higher mean body temperature in the first 4 postoperative days were independent and highly significant predictors for pCMS.CONCLUSIONSThe authors confirmed earlier findings that tumor-associated preoperative conditions, such as a maximum tumor diameter ≥ 5 cm and infiltration into or compression of the brainstem, are associated with a higher risk for the development of pCMS. Most importantly, the authors found that a 0.5°C higher mean body temperature in the first 4 postoperative days increased the odds ratio for the development of pCMS almost 5-fold. These data suggest that an important focus for the prevention of pCMS in children who have undergone medulloblastoma surgery might be rigorous maintenance of normothermia as standard care after surgery.

Objective Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Design Cross-sectional study based on retrospective data. Methods We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5–23 years). Initial craniopharyngioma treatment approaches included gross total resection (n = 25), subtotal resection without radiotherapy (n = 44), subtotal resection with radiotherapy (n = 25), cyst aspiration without radiotherapy (n = 8), and 90Yttrium brachytherapy (n = 21). Results Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Conclusions Long-term health conditions were comparable after different initial craniopharyngioma treatment approaches and were generally more frequent in patients with childhood- compared with adult-onset disease.

Background Surgery for sagittal synostosis aims at correction of skull shape and restoration of growth potential. Small cranial volume is associated with raised intracranial pressure (ICP). Although many techniques have been described, information on postoperative volume related to early and late remodeling is lacking. Methods Between 2004 and 2008, a total of 95 patients were collected who underwent either early extended strip craniectomy or late total cranial remodeling according to age of presentation. Volume was measured on three-dimensional (3D) photogrammetry. Volume measurements were related to cranial index (CI), head circumference (HCsd), and signs of raised ICP. In a small subset of patients, volume measurements on 3D photogrammetry were assessed for inter- and intrarater reliability and compared to 3D computed tomography (CT). Results Volume was increased in all patients before and after surgery compared to normative values. Postoperatively, late total cranial remodeling resulted in a slightly larger volume than early extended strip craniectomy. Volume measurements showed a good correlation with HCsd (0.67) and a poor relationship with CI (0.13). Headache occurred more frequently in patients with a lower cranial volume. Although papilledema and reoperation showed the same trend, the numbers were too small for statistical analysis. Reproducibility of volume measurements on 3D photogrammetry was high, as was the correlation with measurements on CT. Conclusion Late total cranial remodeling results in a larger postoperative volume, as measured on 3D photogrammetry, than extended strip craniectomy. Clinical signs of raised ICP occur more frequently in patients with a smaller volume. To measure volume, 3D photogrammetry is a good alternative to CT.

OBJECTIVEUnicoronal synostosis results in frontal plagiocephaly and is preferably treated before the patient is 1 year of age to prevent intracranial hypertension (ICH). However, data on the prevalence of ICH in these patients is currently lacking. This study aimed to establish the prevalence of preoperative and postoperative signs of ICH in a large cohort of patients with unicoronal synostosis and to test whether there is a correlation between papilledema and occipitofrontal head circumference (OFC) curve stagnation in unicoronal synostosis.METHODSThe authors included all patients with unicoronal synostosis treated before 2 years of age at a single center between 2003 and 2013. The presence of ICH was evaluated by routine fundoscopy. The OFC growth curve was analyzed for deflection and in relationship to signs of ICH.RESULTSIn total, 104 patients were included in this study, 84 (81%) of whom were considered to have nonsyndromic unicoronal synostosis. Preoperatively, none of the patients had papilledema as determined by fundoscopy (mean age at surgery 11 months). Postoperatively, 5% of patients with syndromic synostosis and 3% of those with nonsyndromic synostosis had papilledema, and this was confirmed by optical coherence tomography. Raised intracranial pressure was confirmed in 1 patient with syndromic unicoronal synostosis. Six of 78 patients had OFC stagnation, which was not significantly correlated to papilledema (p = 0.22). One child with syndromic unicoronal synostosis required repeated surgery for ICH (0.96%).CONCLUSIONSPapilledema was not found in patients with unicoronal synostosis when they underwent surgery before the age of 1 year and was also very rare during follow-up. There was no relationship between papilledema and OFC stagnation.

OBJECTIVEImprovements in imaging and surgical technological innovations have led to the increasing implementation of fetal surgical techniques. Open fetal surgery has demonstrated more favorable clinical outcomes in children born with open myelomeningocele (MMC) than those following postnatal repair. However, primarily because of maternal risks but also because of fetal risks, fetal surgery for MMC remains controversial. Here, the authors evaluated the contemporary management of MMC in the hope of identifying barriers and facilitators for neurosurgeons in providing fetal surgery for MMC.METHODSAn online survey was emailed to members of the Congress of Neurological Surgeons (CNS) and the International Society for Pediatric Neurosurgery (ISPN) in March 2019. The survey focused on 1) characteristics of the respondents, 2) the practice of counseling on and managing prenatally diagnosed MMC, and 3) barriers, facilitators, and expectations of fetal surgery for MMC. Reminders were sent to improve the response rate.RESULTSA total of 446 respondents filled out the survey, most (59.2%) of whom specialized in pediatric neurosurgery. The respondents repaired an average of 9.6 MMC defects per year, regardless of technique. Regardless of the departments in which respondents were employed, 91.0% provided postnatal repair of MMC, 13.0% open fetal repair, and 4.9% fetoscopic repair. According to the surgeons, the most important objections to performing open fetal surgery were a lack of cases available to become proficient in the technique (33.8%), the risk of maternal complications (23.6%), and concern for fetal complications (15.2%). The most important facilitators according to advocates of prenatal closure are a decreased rate of shunt dependency (37.8%), a decreased rate of hindbrain herniation (27.0%), and an improved rate of motor function (18.9%). Of the respondents, only 16.9% agreed that open fetal surgery should be the standard of care.CONCLUSIONSThe survey results showed diversity in the management of patients with MMC. In addition, significant diversity remains regarding fetal surgery for MMC closure. Despite the apparent benefits of open fetal surgery in selected pregnancies, only a minority of centers and providers offer this technique. As a more technically demanding technique that requires multidisciplinary effort with less well-established long-term outcomes, fetoscopic surgery may face similar limited implementation, although the surgery may pose fewer maternal risks than open fetal surgery. Centralization of prenatal treatment to tertiary care referral centers, as well as the use of sophisticated training models, may help to augment the most commonly cited objection to the implementation of prenatal closure, which is the overall limited caseload.

Background: This study investigates the relationship between headache and the occurrence of signs associated with intracranial hypertension such as ophthalmic signs, restricted skull growth, and a vertex bulge in children who were operated on for sagittal synostosis. Methods: A total of 94 patients (aged 6 to 18 years) with sagittal synostosis were asked to indicate their headache frequency. Based on their age at referral, the patients had undergone either frontobiparietal remodeling or an extended strip craniotomy. Data on funduscopy, optical coherence tomography, occipitofrontal head circumference, and presence of vertex bulge on radiography were collected retrospectively. Results: Univariate analysis showed that extended strip craniotomy, the occurrence of ophthalmic signs, and a smaller occipitofrontal head circumference at last follow-up were related to more frequent headaches (p = 0.01, p = 0.04, and p < 0.01, respectively). On multivariate analysis, only type of surgery and occipitofrontal head circumference at last follow-up remained significant predictors (p = 0.04 and p < 0.01, respectively). Conclusions: Although the reported rate of frequent headaches in this study is within the norm reported for the normal population, this study shows that after correction for sagittal craniosynostosis, frequent headaches are independently related to type of surgery and to occipitofrontal head circumference at last follow-up. Headaches in the sagittal craniosynostosis population may be related to papilledema and/or an increased total retinal thickness. Therefore, the authors recommend that occipitofrontal head circumference be routinely measured and that patients be asked about the occurrence and frequency of headaches during their checkup at the clinic. (Plast. Reconstr. Surg. 143: 798e, 2019.)

OBJECTIVEIn addition to craniocerebral disproportion, other factors, such as Chiari malformation type I, obstructive sleep apnea, and venous outflow obstruction, are considered to have a role in the occurrence of intracranial hypertension in craniosynostosis. This pilot study examined cerebral venous flow velocity to better characterize the complex intracranial venous physiology of craniosynostosis.METHODSThe authors performed a prospective cohort study of craniosynostosis patients (n = 34) referred to a single national (tertiary) craniofacial unit. Controls (n = 28) consisted of children who were referred to the unit’s outpatient clinic and did not have craniosynostosis. Transfontanelle ultrasound scans with venous Doppler flow velocity assessment were performed at the first outpatient clinic visit and after each surgery, if applicable. Mean venous blood flow velocities of the internal cerebral vein (ICVv) and the superior sagittal sinus (SSSv) were recorded and blood flow waveform was scored.RESULTSPreoperatively, SSSv was decreased in craniosynostosis patients compared with controls (7.57 vs 11.31 cm/sec, p = 0.009). ICVv did not differ significantly between patients and controls. Postoperatively, SSSv increased significantly (7.99 vs 10.66 cm/sec, p = 0.023). Blood flow waveform analyses did not differ significantly between patients and controls.CONCLUSIONSPremature closure of cranial sutures was associated with decreased SSSv but not ICVv; indicating an effect on the superficial rather than deep venous drainage. Further Doppler ultrasound studies are needed to test the hypothesis that at an early stage of craniosynostosis pathology SSSv, but not pulsatility, is abnormal, and that abnormality in both SSSv and the superficial venous waveform reflect a more advanced stage of evolution in suture closure.

Background The mucopolysaccharidoses are multisystem lysosomal storage diseases characterized by extensive skeletal deformities, including skull abnormalities. The objective of this study was to determine the incidence of craniosynostosis in the different mucopolysaccharidosis (MPS) types and its clinical consequences. Methods In a prospective cohort study spanning 10 years, skull imaging and clinical evaluations were performed in 47 MPS patients (type I, II, VI, and VII). A total of 215 radiographs of the skull were analyzed. The presence and type of craniosynostosis, the sutures involved, progression over time, skull shape, head circumference, fundoscopy, and ventriculoperitoneal shunt (VPS) placement data were evaluated. Results Craniosynostosis of at least one suture was present in 77% of all 47 MPS patients (≤ 6 years of age in 40% of all patients). In 32% of all MPS patients, premature closure of all sutures was seen (≤ 6 years of age in 13% of all patients). All patients with early closure had a more severe MPS phenotype, both in the neuronopathic (MPS I, II) and non-neuronopathic (MPS VI) patient groups. Because of symptomatic increased intracranial pressure (ICP), a VPS was placed in six patients, with craniosynostosis as a likely or certain causative factor for the increased pressure in four patients. One patient underwent cranial vault expansion because of severe craniosynostosis. Conclusions Craniosynostosis occurs in the majority of MPS patients. Since the clinical consequences can be severe and surgical intervention is possible, skull growth and signs and symptoms of increased ICP should be monitored in both neuronopathic and non-neuronopathic patients with MPS. Electronic supplementary material The online version of this article (10.1007/s10545-018-0212-1) contains supplementary material, which is available to authorized users.

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.

Why craniosynostosis patients develop elevated intracranial pressure (ICP) is still a mystery. Our aim was to investigate jugular foramen size and its relation to venous hypertension and elevated ICP. Secondly, we evaluated whether occipital collateral veins develop as a compensatory mechanism for elevated ICP. We conducted a prospective study in 41 children with craniosynostosis who underwent a 3D-CT-angiography. We evaluated the anatomical course of the jugular vein, the diameter of the jugular foramen and the relation to the presence of papilledema. Additionally, we studied the anatomical variations of the cerebral venous drainage system. The diameter of the jugular foramen was significantly smaller in our patients. Abnormal venous collaterals were most often observed in patients with Apert, Crouzon Pfeiffer and Saethre Chotzen syndrome, even in children under two years of age. There was no significant difference in the number of collateral veins in patients with or without papilledema. Collaterals appear to reflect an inborn abnormality of the venous system, rather than a compensating mechanism for elevated ICP. This study confirms the presence of jugular foraminal narrowing in craniosynostosis patients and an abnormal venous system, which may predispose to elevated ICP. Level of Evidence: Diagnostic II. (C) 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The purpose of this study was to examine the relationship of head growth, obstructive sleep apnea, and intracranial hypertension in patients with syndromic or complex craniosynostosis, and to evaluate the authors' standardized treatment protocol for the management of intracranial hypertension in these patients.The authors conducted a prospective observational cohort study of patients with syndromic craniosynostosis at a national referral center, treated according to a standardized protocol. Measurements included occipitofrontal head circumference, with growth arrest defined as downward deflection in occipitofrontal head circumference trajectory greater than or equal to a 0.5 SD fall from baseline over 2 years, or lack of change in occipitofrontal head circumference growth curve; sleep studies, with results dichotomized into no/mild versus moderate/severe obstructive sleep apnea; and funduscopy to indicate papilledema, supplemented by optical coherence tomography and/or intracranial pressure monitoring to identify intracranial hypertension.The authors included 62 patients, of whom 21 (33.9 percent) had intracranial hypertension, 39 (62.9 percent) had obstructive sleep apnea, and 20 (32.3 percent) had occipitofrontal head circumference growth arrest during the study. Age at which intracranial hypertension first occurred was 2.0 years (range, 0.4 to 6.0 years). Preoperatively, 13 patients (21.0 percent) had intracranial hypertension, which was associated only with moderate/severe obstructive sleep apnea (p = 0.012). In the first year after surgery, intracranial hypertension was particularly related to occipitofrontal head circumference growth arrest (p = 0.006). Beyond 1 year after surgery, intracranial hypertension was associated with a combination of occipitofrontal head circumference growth arrest (p0.001) and moderate/severe obstructive sleep apnea (p = 0.007).Children with syndromic craniosynostosis are at risk of intracranial hypertension. The major determinant of this after vault expansion is impaired head growth, which may occur at varying ages. The presence of moderate/severe obstructive sleep apnea also significantly increases the risk of intracranial hypertension.Risk, III.

Our aim was to evaluate if optical coherence tomography (OCT) can be used as an alternative for fundoscopy to screen for increased intracranial pressure (ICP) in children with craniosynostosis We performed a prospective cohort study at the Dutch Craniofacial Centre. We included 38 patients with nonsyndromic scaphocephaly and Crouzon's syndrome aged 3-8 years old, in whom we scored complaints suggestive of increased ICP and performed fundoscopy and OCT. Main outcome measures total retinal thickness (TRT) which was measured on 58 OCT scans. Forty-three percent of fundoscopies revealed pathologic changes of the papil in at least one eye. Retinal thickness was increased in patients with an abnormal fundoscopy as compared to patients with a normal papil (TRT p < 0.001). Patients with Crouzon's syndrome had a significantly increased retinal thickness as compared to patients with scaphocephaly (TRT p < 0.001). The current study demonstrates that OCT in children with craniosynostosis is feasible. It confirms that retinal thickness increases in case of papilledema. Given the quantitative character, OCT has a high potential as an alternative tool to screen for papilledema in craniosynostosis and other pediatric populations.