Anatomy and mobility in the adult cadaveric craniocervical junction.

Genetic diseases with craniofacial malformations can be associated with anomalies of the craniocervical joint (CCJ). The functions of the CCJ are thus impaired, as mobility may be either limited by abnormal bone fusion causing headaches, or exaggerated in the case of hypermobility, which may cause irreparable damage to the spinal cord. Restoring the balance between mobility and stability requires surgical correction in children. The anatomy and biomechanics of the CCJ are quite unique, yet have been overlooked in the past decades. Pediatric evidence is so scarce, that investigating the adult CCJ is our best shot to disentangle the form-function relationships of this anatomical region. The motivation of the present study was to understand the morphological and functional basis of motion in the CCJ, in the hope to find morphological features accessible from medical imaging able to predict mobility. To do so, we have quantified the in-vitro kinematics of the CCJ in nine cadaveric asymptomatic adults, and estimated a wide range of mobility variables covering the complexity of spinal motion. We compared these variables with the shape of the occipital, the atlas and the axis, obtained using a dense geometric morphometric approach. Morphological joint congruence was also quantified. Our results suggest a strong relationship between bone shape and motion, with the overall geometry predicting best the primary movements, and the joint facets predicting best the secondary movements. We propose a functional hypothesis stating that the musculoligamental system determines movements of great amplitude, while the shape and congruence of joint facets determine the secondary and coupled movements, especially by varying the geometry of bone stops and the way ligaments are tensioned. We believe this work will provide valuable insights in understanding the biomechanics of the CCJ. Furthermore, it should help surgeons treating CCJ anomalies by enabling them to translate objectives of functional and clinical outcome into clear objectives of morphological outcome.

Distractor position and distraction amplitude in fronto-facial monobloc advancement : A case series.

Fronto-facial monobloc advancement with internal distraction (FFMBA) is a central procedure in the management of faciocraniosynostoses. In techniques with internal distraction, two sets of devices are generally positioned: bilateral fronto-orbital and temporo-zygomatic distractors, using a temporal tongue and groove osteotomy design. It is believed that distractors must be positioned as parallel as possible in the horizontal and sagittal planes to avoid mechanical conflicts between the sliding bone fragments of the tongue and groove during distraction, and thus optimize the advancement amplitude. Several approaches involving surgical planification and guides for distractor positioning have thus been proposed to monitor distractor placement. To explore the need for surgical planification in distractor placement, the parallelism of the position of the 4 distractors was assessed in 19 FFMBA procedures and we correlated a set of 10 distractor angles with the degree of advancement. We report that the horizontal cut of the tongue and groove can be used as a landmark for the positioning of the lower, temporo-zygomatic, distractor in fronto-facial monobloc advancement. Other parameters (relative position of the two homolateral and the two contralateral distractors and the orientations of the vertical and horizontal cuts of the tongue and groove) do not interfere with distraction, other things being equal. Our results indicate that distractor orientation is not a critical issue in fronto-facial monobloc advancement when devices are positioned as parallel as possible based on visual monitoring.

New diagnostic criteria for metopic ridges and trigonocephaly: a 3D geometric approach.

BACKGROUND: Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly. METHODS: Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification. RESULTS: We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures. CONCLUSION: Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools.

Geometric growth of the normal human craniocervical junction from 0 to 18 years old.

The craniocervical junction (CCJ) forms the bridge between the skull and the spine, a highly mobile group of joints that allows the mobility of the head in every direction. The CCJ plays a major role in protecting the inferior brainstem (bulb) and spinal cord, therefore also requiring some stability. Children are subjected to multiple constitutive or acquired diseases involving the CCJ: primary bone diseases such as in FGFR-related craniosynostoses or acquired conditions such as congenital torticollis, cervical spine luxation, and neurological disorders. To design efficient treatment plans, it is crucial to understand the relationship between abnormalities of the craniofacial region and abnormalities of the CCJ. This can be approached by the study of control and abnormal growth patterns. Here we report a model of normal skull base growth by compiling a collection of geometric models in control children. Focused analyses highlighted specific developmental patterns for each CCJ bone, emphasizing rapid growth during infancy, followed by varying rates of growth and maturation during childhood and adolescence until reaching stability by 18 years of age. The focus was on the closure patterns of synchondroses and sutures in the occipital bone, revealing distinct closure trajectories for the anterior intra-occipital synchondroses and the occipitomastoid suture. The findings, although based on a limited dataset, showcased specific age-related changes in width and closure percentages, providing valuable insights into growth dynamics within the first 2 years of life. Integration analyses revealed intricate relationships between skull and neck structures, emphasizing coordinated growth at different stages. Specific bone covariation patterns, as found between the first and second cervical vertebrae (C1 and C2), indicated synchronized morphological changes. Our results provide initial data for designing inclusive CCJ geometric models to predict normal and abnormal growth dynamics.

A European multicenter outcome study on the different perioperative airway management policies following midface surgery in syndromic craniosynostosis: a proposal for a Standard Operating Procedure.

BACKGROUND: Perioperative airway management following midface advancements in children with Apert and Crouzon/Pfeiffer syndrome can be challenging, and protocols often differ. This study examined airway management following midface advancements and postoperative respiratory complications. METHODS: A multicenter, retrospective cohort study was performed to obtain information about the timing of extubation, perioperative airway management, and respiratory complications after monobloc / le Fort III procedures. RESULTS: Ultimately, 275 patients (129 monobloc and 146 Le Fort III) were included; 62 received immediate extubation and 162 delayed extubation; 42 had long-term tracheostomies and nine perioperative short-term tracheostomies. Short-term tracheostomies were in most centers reserved for selected cases. Patients with delayed extubation remained intubated for three days (IQR 2 - 5). The rate of no or only oxygen support after extubation was comparable between patients with immediate and delayed extubation, 58/62 (94%) and 137/162 (85%) patients, respectively. However, patients with immediate extubation developed less postoperative pneumonia than those with delayed, 0/62 (0%) versus 24/161 (15%) (P = 0.001), respectively. Immediate extubation also appeared safe in moderate/severe OSA since 19/20 (95%) required either no or only oxygen support after extubation. The odds of developing intubation-related complications increased by 21% with every extra day of intubation. CONCLUSIONS: Immediate extubation following midface advancements was found to be a safe option, as it was not associated with respiratory insufficiency but did lead to fewer complications. Immediate extubation should be considered routine management in patients with no/mild OSA and should be the aim in moderate/severe OSA after careful assessment.

Mobility Assessment Using Multi-Positional MRI in Children with Cranio-Vertebral Junction Anomalies.

OBJECTIVE: This study aimed to assess the relevance of using multi-positional MRI (mMRI) to identify cranio-vertebral junction (CVJ) instability in pediatric patients with CVJ anomalies while determining objective mMRI criteria to detect this condition. MATERIAL AND METHODS: Data from children with CVJ anomalies who underwent a mMRI between 2017 and 2021 were retrospectively reviewed. Mobility assessment using mMRI involved: (1) morphometric analysis using hierarchical clustering on principal component analysis (HCPCA) to identify clusters of patients by considering their mobility similarities, assessed through delta (Δ) values of occipito-cervical parameters measured on mMRI; and (2) morphological analysis based on dynamic geometric CVJ models and analysis of displacement vectors between flexion and extension. Receiver operating characteristics (ROC) curves were generated for occipito-cervical parameters to establish instability cut-off values. (3) Additionally, an anatomical qualitative analysis of the CVJ was performed to identify morphological criteria of instability. RESULTS: Forty-seven patients with CVJ anomalies were included (26 females, 21 males; mean age: 10.2 years [3-18]). HCPCA identified 2 clusters: cluster №1 (stable patients, n = 39) and cluster №2 (unstable patients, n = 8). ΔpB-C2 (pB-C2 line delta) at ≥2.5 mm (AUC 0.98) and ΔBAI (Basion-axis Interval delta) ≥ 3 mm (AUC 0.97) predicted instability with 88% sensibility and 95% specificity and 88% sensitivity and 85% specificity, respectively. Geometric CVJ shape analysis differentiated patients along a continuum, from a low to a high CVJ motion that was characterized by a subluxation of C1 in the anterior direction. Qualitative analysis found correlations between instability and C2 anomalies, including fusions with C3 (body p = 0.032; posterior arch p = 0.045; inferior articular facets p = 0.012; lateral mass p = 0.029). CONCLUSIONS: We identified a cluster of pediatric patients with CVJ instability among a cohort of CVJ anomalies that were characterized by morphometric parameters with corresponding cut-off values that could serve as objective mMRI criteria. These findings warrant further validation through prospective case-control studies.

Predicting endoscopic third ventriculostomy success in pediatric shunt dysfunction: a monocentric retrospective case series of 70 consecutive children, systematic review, and meta-analysis.

OBJECTIVE: The outcome of endoscopic third ventriculostomy (ETV) in children who had previously received shunts and who were experiencing shunt dysfunction is still discussed in terms of efficacy (success rate from 40% to 80%) and safety (0%-32.5% of complications). Reported predictive factors of secondary ETV failure are age, early onset of hydrocephalus, and prematurity. The best surgical strategy in the different subgroups of patients with shunt dysfunction is still debated. Therefore, the authors aimed to identify subgroups of patients in whom shunt treatment was associated with favorable outcome of ETV, to define the role of ETV in patients with global rostral midbrain dysfunction syndrome. METHODS: This study was a monocentric retrospective case series and a meta-analysis of children who had previously received shunts and who underwent secondary ETV for shunt dysfunction between 2012 and 2022. Clinical and MRI features were examined, along with surgical outcome, etiology of hydrocephalus, and preoperative ETV Success Score. Univariate and multivariate analyses were performed to find predictors of outcome of secondary ETV. Youden's J index was calculated on age distribution to find an optimal age cutoff. Systematic review of the literature and a meta-analysis were performed according to the PRISMA statement. RESULTS: Seventy consecutive patients were included. The overall success rate of secondary ETV was 63%. Primary obstructive hydrocephalus, age ≥ 36 months, and the presence of aqueductal obstruction were predictors of ETV success. Multivariate analysis found that age < 36 months, primary inflammatory hydrocephalus, and presence of fourth ventricular obstruction were associated with ETV failure. All patients with global rostral midbrain dysfunction syndrome experienced clinical and radiological improvement after ETV. The meta-analysis showed that postinflammatory etiology and age < 36 months were predictors of ETV failure. CONCLUSIONS: ETV is safe and effective for children with obstructive hydrocephalus experiencing shunt dysfunction, notably in cases of primary obstructive hydrocephalus with aqueductal stenosis, and among children whose age was ≥ 36 months who had postinflammatory hydrocephalus.

Cerebral ischemia: a frequent complication of large traumatic epidural hematoma in infants.

OBJECTIVE: Epidural hematoma (EDH) has rarely been studied specifically in infants. The objective of this study was to investigate the outcomes of patients aged < 18 months (infants) with EDH. METHODS: The authors conducted a single-center retrospective study of 48 infants aged less than 18 months who underwent an operation for a supratentorial EDH in the last decade. Clinical, radiological, and biological variables were used in a statistical analysis to identify factors predictive of radiological and clinical outcome. RESULTS: Forty-seven patients were included in the final analysis. Seventeen children (36%) had cerebral ischemia on postoperative imaging, either due to stroke (cerebral herniation) or by local compression. Factors associated with ischemia after multivariate logistic regression were the presence of an initial neurological deficit (76% vs 27%, p = 0.03), low platelet count (mean 192 vs 267 per mm3, p = 0.01), low fibrinogen level (mean 1.4 vs 2.2 g/L, p = 0.04) and long intubation time (mean 65.7 vs 10.1 hours, p = 0.03). Cerebral ischemia on MRI was predictive of a poor clinical outcome. CONCLUSIONS: Infants with EDH have a low mortality rate but a high risk of cerebral ischemia, along with long-term neurological sequelae.

The Management of Hydrocephalus in Midline Posterior Fossa Cystic Collections: Surgical Outcome From a Retrospective Single-Center Case Series of 54 Consecutive Pediatric Patients.

BACKGROUND: Hydrocephalus frequently occurs with midline posterior fossa cystic collections. The classification of this heterogeneous group of developmental anomalies, including Dandy-Walker malformation, persisting Blake's pouch, retrocerebellar arachnoid cysts, and mega cisterna magna, is subject of debate. The absence of diagnostic criteria is confusing regarding the ideal management of PFCC-related hydrocephalus. OBJECTIVE: To decipher the surgical strategy for the treatment of children with PFCC-related hydrocephalus through a retrospective analysis of the surgical outcome driven by their clinical and radiological presentation. METHODS: This study enrolled patients operated of symptomatic PFCC-related hydrocephalus. Clinical and MRI features were examined, as well as the surgical outcome. Unbiased subgroup classification of the patients was performed with multiple component analysis as a function of imaging characteristics and hierarchical clustering on principal component. Outcome was assessed with binomial logistic regression and Kaplan-Meier analysis. RESULTS: Fifty-four patients were included between 2007 and 2021. Multiple component analysis suggested that cerebellar and vermian hypoplasia, vermian rotation, basal-tentorial angle, and fastigial angle were strongly correlated. Hierarchical clustering and the distribution of the patients in the bidimensional plot showed the clear segregation of 3 major clusters, which correlated with the radiological diagnosis ( P < .01). Binomial logistic regression and survival analysis showed that endoscopic third ventriculostomy was an effective treatment for patients with persisting Blake's pouch, while failing to control hydrocephalus in most of patients with Dandy-Walker malformation. CONCLUSION: Preoperative MRI in patients with PFCC-related hydrocephalus is essential to better define the diagnosis. The choice of treatment strategy notably relies on correct radiological diagnosis.

Comparison of Internal and External Distraction in Frontofacial Monobloc Advancement: A Three-Dimensional Quantification.

BACKGROUND: Crouzon syndrome is characterized by complex craniosynostosis and midfacial hypoplasia. Where frontofacial monobloc advancement (FFMBA) is indicated, the method of distraction used to achieve advancement holds an element of equipoise. This two-center retrospective cohort study quantifies the movements produced by internal or external distraction methods used for FFMBA. Using shape analysis, this study evaluates whether the different distraction forces cause plastic deformity of the frontofacial segment, producing distinct morphologic outcomes. METHODS: Patients with Crouzon syndrome who underwent FFMBA with internal distraction [Hôpital Necker-Enfants Malades (Paris, France)] or external distraction [Great Ormond Street Hospital for Children (London, United Kingdom)] were compared. Digital Imaging and Communications in Medicine files of preoperative and postoperative computed tomographic scans were converted to three-dimensional bone meshes and skeletal movements were assessed using nonrigid iterative closest point registration. Displacements were visualized using color maps and statistical analysis of the vectors was undertaken. RESULTS: Fifty-one patients met the strict inclusion criteria. Twenty-five underwent FFMBA with external distraction and 26 with internal distraction. External distraction provides a preferential midfacial advancement, whereas internal distractors produce a more positive movement at the lateral orbital rim. This confers good orbital protection but does not advance the central midface to the same extent. Vector analysis confirmed this to be statistically significant ( P < 0.01). CONCLUSIONS: Morphologic changes resulting from monobloc surgery differ depending on the distraction technique used. Although the relative merits of internal and external distraction still stand, it may be that external distraction is more suited to addressing the midfacial biconcavity seen in syndromic craniosynostosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Chiari malformation type I surgery in children: French multicenter 10-year cohort.

OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.

Impact of sleep-disordered breathing on the management of children with Chiari malformation type I.

OBJECTIVES: Children with Chiari malformation type I (CM-I) have an increased risk of sleep apnea. The aim of the study was to describe the management of CM-I patients in relation to symptoms, magnetic resonance imaging (MRI) findings and sleep apnea syndrome (SAS). METHODS: We performed a retrospective analysis of clinical charts of all 57 CM-I patients seen between September 2013 and April 2017. RESULTS: A total of 45 patients had isolated CM-I or associated co-morbidity (CM-Iia), 5 had craniosynostosis (CM-Ics), and 7 a polymalformative syndrome (CM-Ipm). The prevalence of SAS, defined as an apnea-hypopnea index >1 event/h, was high in CM-I ranging from 50% to 80% according to the CM-I group. The prevalence of central sleep apnea (CSA) was low, with 5 (9%) patients having CSA and only 3 patients with CM-Iia having isolated CSA. A total of 17 patients (30%) had foramen magnum decompression (FMD). Neither positive symptoms of CM-I nor MRI findings alone, nor both combined were good indicators for FMD. No correlation was observed between the cerebellar tonsil descent and SAS in CM-I. But all 5 patients with CSA had a FMD. The combination of MRI findings and/or symptoms of CM-I together with moderate-to-severe SAS best discriminated patients who needed a FMD. CONCLUSION: Our findings highlight the importance of a combined evaluation of symptoms, MRI and polygraphy results in the management of CM-I patients.

Temporosylvian arachnoid cysts in children. Part 2: Postoperative neuropsychological and clinical improvement.

OBJECTIVE: The authors' objective was to study clinical, imaging, and neuropsychological changes in children who underwent surgery for a temporal arachnoid cyst (TAC). METHODS: Thirty-four children were prospectively assessed similarly at diagnosis and postoperatively (mean 14 months) with clinic visits, images, cognitive tests, and parental questionnaires on mood/behavior and executive functions. The scores were compared pre- and postoperatively for the entire cohort and individually. The scores of 25 children were also compared with a control group of 23 healthy age-matched children. Parents were administered an outcome questionnaire on average 4 years postoperatively. RESULTS: The 34 children selected for surgery had signs of raised intracranial pressure (74%) and/or selective neuropsychological disorders presumably linked to cyst location (learning difficulties in 65%, cognitive difficulties in 56%, and mood/behavior difficulties in 47%). The majority of patients had a convex cyst (85%) and underwent microsurgical fenestration (85%). The TAC volume decreased ≥ 50% for 59% of children. On the Wechsler Intelligence Scale, the entire cohort significantly improved on Full Scale IQ and verbal and perceptual nonverbal indexes. Individually, nearly half of the children (47%) highly increased their scores (≥ 15 points) on at least one IQ index and 26% on at least two indexes. Language, working memory, episodic memory, and executive functions were also significantly improved. Improvements were more pronounced in patients with a preoperative heterogeneous profile with isolated lower scores and a left-sided cyst. Parental questionnaires showed reduction in anxiety, aggressiveness, social problems, and daily life executive disorders. Preschool-aged children improved significantly in language and verbal IQ, as did middle/high school-aged children in many domains. Individual analyses revealed improvement in 76% of cases. Cognitive scores were lower for patients preoperatively than for controls and were no longer significantly different postoperatively in verbal fluency, visual memory, and working memory. Four years later, 97% of parents described an improvement in their child, correlated with cognitive improvements. CONCLUSIONS: Among children with a TAC, some have no clinical signs or neuropsychological difficulties, and others may show signs of raised intracranial pressure and/or specific neuropsychological disorders that impact daily life and require significant and long-lasting rehabilitation. In these cases, consideration may be given to surgical decompression. It is interesting to note that 76% of this surgically treated cohort improved regardless of the child's age, particularly in patients with selective disorders and an impact on daily life. However, a larger number of children will need to be investigated before the true benefit of such treatment can be known.

Temporosylvian arachnoid cysts in children. Part 1: Cognitive profile of children with a temporal cyst and impact of the cyst in daily life. A prospective study in 100 consecutive children.

OBJECTIVE: The aim of this study was to determine the cognitive profile of children with a temporal arachnoid cyst (TAC) and its impact on daily life. METHODS: The authors prospectively analyzed the cognitive and psychological profiles of 100 consecutive children relative to age and cyst characteristics (side, cyst size, and cyst shape: convex or nonconvex) and their outcome 4 years later. RESULTS: Mean IQs were normal but with high heterogeneity on Full Scale IQ (FSIQ; range 59-150); 29% of children had at least one Wechsler index below the norm, in particular, Processing Speed and Working Memory Indexes. Impairments were observed in language for 31% of children, as well as in verbal memory (28%), visual memory (23%), executive function (21%), and visual attention (24%). Half of the children (50%) needed rehabilitation for learning difficulties, and 26% had academic difficulties. The parental questionnaire BRIEF (Behavior Rating Inventory of Executive Function) revealed significant executive dysfunctions in daily life for 22% of the children. One-third of the patients (34%) required psychotherapy for anxiety or social disorders, with higher rates in patients with a right-sided cyst and older children. Cyst size had very little neuropsychological impact. Convex cysts were significantly associated with worse performance than nonconvex cysts on all Wechsler indexes and FSIQ, and in language, verbal memory, attention, and visuospatial skills. Children with a convex cyst had significantly more executive and behavior difficulties in daily life and more psychotherapy than other children. The effect of cyst shape was independent of Galassi type and cyst side. Children with a ruptured cyst or an incidentally discovered cyst usually had a good cognitive level. Four years later, children without initial disorders remained stable, whereas those with difficulties who did not undergo surgery needed more rehabilitation and school adaptations. CONCLUSIONS: This large cohort study revealed a varied profile of children with a TAC: at initial assessment, 50% had neuropsychological difficulties and needed rehabilitation and/or psychotherapy for learning or behavior difficulties, and 50% had no difficulties, which may explain the debate about this pathology. Patients with neuropsychological difficulties had a heterogeneous profile with normal intelligence but selective cognitive and/or behavior disorders that may have a long-term impact on their quality of life, particularly those with a right-sided cyst. A neuropsychological evaluation is not always necessary for a cyst discovered incidentally, but early evaluation is essential in patients with academic, learning, or psychological disorders. When assessment shows selective disorders presumably linked to cyst location, surgery may be considered, particularly for convex cysts, as this study revealed more effects in association with cyst shape than with cyst size and significantly poorer performance with a convex cyst.

Secondary Le Fort III after Early Fronto-Facial Monobloc Normalizes Sleep Apnea in Faciocraniosynostosis: A Cohort Study.

BACKGROUND: This study aims to assess the improvement of sleep apnea after secondary Le Fort III facial advancement with distraction (LF3) in faciocraniosynostosis (FCS) patients with sleep apnea who have previously undergone fronto-facial monobloc advancement (FFMBA) with distraction. METHODS: Patients having undergone secondary LF3 were selected from a cohort of FCS patients with documented sleep apnea who had previously undergone fronto-facial monobloc advancement. Patient charts and polysomnographic records were reviewed. Apnea-hypopnea index (AHI) was recorded before and at least 6 months after secondary LF3. The primary outcome was normalization of AHI (less than 5/h was considered normal). Hierarchical multilevel analysis was performed to predict postoperative AHI evolution. RESULTS: Seventeen patients underwent a secondary LF3, 7.0 ± 3.9 years after the primary FFMBA. The mean age was 9.6 ± 3.9 years. A total of 15 patients (88%) normalized their AHI. Two of four patients were decannulated (50%). There was a statistically significant decrease in AHI (preoperative AHI 21.5/h vs. 3.9/h postoperatively, p=0.003). Hierarchic multilevel modeling showed progressive AHI decrease postoperatively. CONCLUSION: Secondary LF3 improves residual or relapsing sleep apnea in FCS patients who have previously had FFMBA.

Growth charts in FGFR2- and FGFR3-related faciocraniosynostoses.

Objective: Faciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial sutures, mostly secondary to activating Fibroblast Growth Factor Receptor (FGFR) 1-3 mutations. Gain-of-function FGFR3 mutations are also responsible for various conditions referred to as osteochondrodysplasia (OCD), characterized by structural and functional abnormalities of growth plate cartilages. We hypothesized that patients with FGFR-related faciocraniosynostoses may present extra-cranial growth anomalies. Study design: We retrospectively collected height and weight data from a cohort of 70 patients. Included patients were admitted for FGFR-related FCS between 2000 and 2021 at the Craniofacial Unit of Necker - Enfants Malades University Hospital in Paris, France. Results: We showed that FGFR-related faciocraniosynostoses had significantly reduced heights and weights relative to controls, and that two specific time periods (1-3 years and > 8 years of age) were associated with lower height and weight values. Four patients had received growth hormone treatment but remained below normal values for growth in height and weight. Conclusions: Patients with FGFR-related faciocraniosynostoses have clinically significant extra-cranial anomalies which are not currently investigated and managed in usual protocols; these patients could benefit from a systematic pre-pubertal endocrine assessment. More generally, our results extend the scope of extracranial anomalies in FGFR-related faciocraniosynostoses and support the hypothesis that all conditions with activating FGFR mutations affect both membranous ossification and long bones.

FGFR3 overactivation in the brain is responsible for memory impairments in Crouzon syndrome mouse model.

Crouzon syndrome with acanthosis nigricans (CAN, a rare type of craniosynostosis characterized by premature suture fusion and neurological impairments) has been linked to a gain-of-function mutation (p.Ala391Glu) in fibroblast growth factor receptor 3 (FGFR3). To characterize the CAN mutation's impact on the skull and on brain functions, we developed the first mouse model (Fgfr3A385E/+) of this syndrome. Surprisingly, Fgfr3A385E/+ mice did not exhibit craniosynostosis but did show severe memory impairments, a structurally abnormal hippocampus, low activity-dependent synaptic plasticity, and overactivation of MAPK/ERK and Akt signaling pathways in the hippocampus. Systemic or brain-specific pharmacological inhibition of FGFR3 overactivation by BGJ398 injections rescued the memory impairments observed in Fgfr3A385E/+ mice. The present study is the first to have demonstrated cognitive impairments associated with brain FGFR3 overactivation, independently of skull abnormalities. Our results provide a better understanding of FGFR3's functional role and the impact of its gain-of-function mutation on brain functions. The modulation of FGFR3 signaling might be of value for treating the neurological disorders associated with craniosynostosis.

Management of sagittal craniosynostosis: morphological comparison of eight surgical techniques.

The aim of this study was to carry out a retrospective multicentre study comparing the morphological outcome of 8 techniques used for the management of sagittal synostosis versus a large cohort of control patients. Computed tomographic (CT) images were obtained from children CT-scanned for non-craniosynostosis related events (n = 241) and SS patients at preoperative and postoperative follow-up stages (n = 101). No significant difference in morphological outcomes was observed between the techniques considered in this study. However, the majority of techniques showed a tendency for relapse. Further, the more invasive procedures at older ages seem to lead to larger intracranial volume compared to less invasive techniques at younger ages. This study can be a first step towards future multicentre studies, comparing surgical results and offering a possibility for objective benchmarking of outcomes between methods and centres.

Scaphocephaly and increased intra-cranial pressure in non-operated adults: A controlled anthropological study on 21 skulls.

AIM AND SCOPE: The prevalence of increased intra-cranial pressure (ICP) in patients with scaphocephaly is controversial. Here, based on anthropological material, we aimed to determine whether adults with non-operated sagittal synostosis show indirect signs of increased ICP. MATERIALS AND METHODS: Thirty-eight dry skulls (21 skulls with sagittal craniosynostosis and 17 controls) were selected from the collections of the National Museum of Natural History (Paris, France). All skulls registered as 'fused sagittal suture' or 'scaphocephaly' in the registry of the Museum were included. All had total fusion of the sagittal suture. Controls were selected within skulls of similar origin (France), without visible craniofacial anomalies. The 38 skulls were CT-scanned using a standard medical CT-scan with a protocol dedicated to dry bone imaging. Eight radiological signs associated with raised ICP were assessed: (1) calvaria and (2) skull base thinning, (3) dorsum sellae erosion, (4) sella turcica lengthening, (5) copper beaten skull, (6) suture diastasis, (7) persistent metopic suture, and (8) small frontal sinus. Scaphocephaly was assessed based on head circumference, cranial index, intra-cranial volume, fronto-nasal angle, and inter-zygomatic distance. Linear and non-linear logistic models were used to compare groups. RESULTS: 19/21 skulls with sagittal synostosis were significantly scaphocephalic. None of the criteria for ICP were significantly different in skulls with scaphocephaly relative to controls. Nevertheless, 5 individual skulls with scaphocephaly had ≥ 3 signs in favor of a history of raised ICP. We do not report the significant prevalence of indirect signs of raised ICP in adults with scaphocephaly. These results do not allow ruling out a history of early raised ICP or of minor prolonged raised ICP. Even though our findings support the fact that scaphocephaly is not significantly associated with prolonged raised ICP, individual cases (5/21) with clear signs in favor of a history of brain compression indicate that scaphocephaly correction should be considered as a functional procedure until the production of clear evidence. Cognitive assessments of non-operated adult patients with scaphocephaly could contribute to tackle this recurring question in craniofacial surgery.

Ophthalmological findings in children with unicoronal craniosynostosis.

INTRODUCTION: Among non-syndromic, single-suture craniosynostoses, unicoronal craniosynostosis (UCS) presents the highest rate of ophthalmic manifestations requiring a visual follow-up, due to the high risk of amblyopia. After birth or during childhood, children with UCS have a high risk to present an aniso-astigmatism and a strabismus. The aim of this study was to characterize clinical ophthalmologic findings associated with UCS in a paediatric cohort. METHODS: This retrospective study included children admitted in our unit between 2015 and 2021, with isolated UCS treated in our institution and complete ophthalmological assessment comprising visual assessment, refractive status and oculomotor examination. Children with associated craniofacial disorders were excluded. RESULTS: A total of 28 children met the inclusion criteria. Median age was 62 [13-192] months with a large proportion of girls (86%) and 71% of right-sided UCS. The mean best corrected visual acuity was 0.07 (±0.13) LogMAR, including 10 (36%) children with an amblyopia or history of amblyopia. Astigmatism was significantly higher on the contralateral side of the UCS than on the ipsilateral side, with a refractive cylinder error of 0.97 (±1.06) vs 0.56 (±0.68) diopters, respectively (p = 0.03). Strabismus was observed in 20 patients (71%) with a main pattern of esotropia with a vertical component. A pseudo-superior oblique palsy was found in 13 children (65%) with a median cyclodeviation of 8.7° [-5,4°-20.6°]. CONCLUSION: Children with UCS experience a high rate of various visual manifestations. This study highlights their need for a strict ophthalmological follow-up, in order to early diagnose and prevent visual complications.