A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens.

Changes in gene regulatory elements play critical roles in human phenotypic divergence. However, identifying the base-pair changes responsible for the distinctive morphology of Homo sapiens remains challenging. Here, we report a noncoding single-nucleotide polymorphism (SNP), rs41298798, as a potential causal variant contributing to the morphology of the skull base and vertebral structures found in Homo sapiens. Screening for differentially regulated genes between Homo sapiens and extinct relatives revealed 13 candidate genes associated with basicranial development, with TBX1, implicated in DiGeorge syndrome, playing a pivotal role. Epigenetic markers and in silico analyses prioritized rs41298798 within a TBX1 intron for functional validation. CRISPR editing revealed that the 41-base-pair region surrounding rs41298798 modulates gene expression at 22q11.21. The derived allele of rs41298798 acts as an allele-specific enhancer mediated by E2F1, resulting in increased TBX1 expression levels compared to the ancestral allele. Tbx1-knockout mice exhibited skull base and vertebral abnormalities similar to those seen in DiGeorge syndrome. Phenotypic differences associated with TBX1 deficiency are observed between Homo sapiens and Neanderthals (Homo neanderthalensis). In conclusion, the regulatory divergence of TBX1 contributes to the formation of skull base and vertebral structures found in Homo sapiens.

In utero nicotine exposure affects murine palate development.

OBJECTIVES: Despite data linking smoking to increased risk of fetal morbidity and mortality, 11% of pregnant women continue to smoke or use alternative nicotine products. Studies confirm that nicotine exposure during pregnancy increases the incidence of birth defects; however, little research has focused on specific anatomic areas based on timing of exposure. We aim to determine critical in utero and postnatal periods of nicotine exposure that affect craniofacial development, specifically palate growth. Malformation of the palatal structures can result in numerous complications including facial growth disturbance, or impeding airway function. We hypothesized that both in utero and postnatal nicotine exposure will alter palate development. MATERIALS AND METHODS: We administered pregnant C57BL6 mice water supplemented with 100 µg/mL nicotine during early pregnancy, throughout pregnancy, during pregnancy and lactation, or lactation only. Postnatal day 15 pups underwent micro-computed tomography (µCT) analyses specific to the palate. RESULTS: Resultant pups revealed significant differences in body weight from lactation-only nicotine exposure, and µCT investigation revealed several dimensions affected by lactation-only nicotine exposure, including palate width, palate and cranial base lengths, and mid-palatal suture width. CONCLUSIONS: These results demonstrate the direct effects of nicotine on the developing palate beyond simple tobacco use. Nicotine exposure through tobacco alternatives, cessation methods, and electronic nicotine delivery systems (ENDS) may disrupt normal growth and development of the palate during development and the postnatal periods of breastfeeding. Due to the recent dramatic increase in the use of ENDS, future research will focus specifically on this nicotine delivery method.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Diagnostic accuracy of intrathecal fluorescein versus other radiological modalities in evaluating non-congenital skull base defects: a systematic review and meta-analysis.

PURPOSE: The intraoperative detection of cerebrospinal fluid (CSF) leaks during endoscopic skull base surgery is critical to ensure watertight sealed defects. Intrathecal fluorescein (ITF) is a valuable adjunct to intraoperative investigation. Hence, our aim is to summarize the evidence of the efficacy of ITF as an accurate diagnostic modality and reconstruction guide for non-congenital skull base defects. METHODS: Using the Cochrane Central, MEDLINE, and Embase databases, we identified studies involving the use of ITF in non-congenital CSF leaks which were published until November 2023. The STATA 18 software was used for meta-analysis. RESULTS: Fourteen studies met the inclusion criteria, in which seven studies were included in the meta-analysis. ITF was used in 1898 (90.3%) of patients, with a detection rate of 88.1%. The overall detection rate of non-congenital CSF leaks among ITF concentrations of 5% and 10% had a statistically significant pooled effect size of 2.6 (95% CI = 2.25, 2.95), while when comparing the ITF to other alternative radiological tests, it was not statistically significant with a mean difference of 0.88 (95% CI = - 0.4, 2.16). Moreover, the pooled prevalence was statistically significant in regards of the complications associated with ITF with an effect size of 0.6 (95% CI = 0.39, 0.82), indicating that 60% of patients who underwent ITF would experience at least one of the measured complications. CONCLUSION: ITF is considered as an efficient tool in localizing skull base defects. However, there was no significant results when comparing the ITF to other alternative radiological tests. Accordingly, if the ITF intervention is indicated, patients should be carefully selected based on their clinical need.

Current trends in craniofacial reconstruction.

Reconstruction of the head and neck continues to pose a variety of difficult functional and aesthetic challenges to the plastic surgeon. While the surgical treatment for midfacial and skull base tumours continues to advance, the three-dimensional reconstruction predicaments continue to increase in complexity. Reconstructive strategies of the head and neck require the restoration of intricate skeletal architecture and large volumes of both internal and external soft tissue envelopes that can withstand adjuvant therapies. Vascularized bone grafts in combination with microsurgical techniques is the current trend of most reconstruction and has replaced local and pedicle flaps as the preferred modality for large defects. This article will focus on concise areas of difficulty in craniofacial reconstruction, including mandibular, midfacial, scalp and base of skull reconstruction. As our goals now move from flap survival to refinement, more complex and innovative reconstructions are executed. The problems with each modality are examined, and the frontiers of head and neck reconstruction are explored. With the potential combination of virtual surgery and tissue engineered biotechnology, we may someday be able to expand our reconstructive capabilities beyond free tissue transfer.

Cranial Neural Crest Specific Deletion of Alpl (TNAP) via P0-Cre Causes Abnormal Chondrocyte Maturation and Deficient Cranial Base Growth.

Bone growth plate abnormalities and skull shape defects are seen in hypophosphatasia, a heritable disorder in humans that occurs due to the deficiency of tissue nonspecific alkaline phosphatase (TNAP, Alpl) enzyme activity. The abnormal development of the cranial base growth plates (synchondroses) and abnormal skull shapes have also been demonstrated in global Alpl-/- mice. To distinguish local vs. systemic effects of TNAP on skull development, we utilized P0-Cre to knockout Alpl only in cranial neural crest-derived tissues using Alpl flox mice. Here, we show that Alpl deficiency using P0-Cre in cranial neural crest leads to skull shape defects and the deficient growth of the intersphenoid synchondrosis (ISS). ISS chondrocyte abnormalities included increased proliferation in resting and proliferative zones with decreased apoptosis in hypertrophic zones. ColX expression was increased, which is indicative of premature differentiation in the absence of Alpl. Sox9 expression was increased in both the resting and prehypertrophic zones of mutant mice. The expression of Parathyroid hormone related protein (PTHrP) and Indian hedgehog homolog (IHH) were also increased. Finally, cranial base organ culture revealed that inorganic phosphate (Pi) and pyrophosphate (PPi) have specific effects on cell signaling and phenotype changes in the ISS. Together, these results demonstrate that the TNAP expression downstream of Alpl in growth plate chondrocytes is essential for normal development, and that the mechanism likely involves Sox9, PTHrP, IHH and PPi.

Cranial Base Angle in Patients With Cleft Lip and Palate-A Systematic Review and Meta-Analysis.

Background: Diverse findings have been reported for the cranial base angle (CBA) in patients with CLP (cleft lip and palate) and non-CLP controls. Objective: The aim of this study is to assess and evaluate the CBA in patients with CLP and non-CLP controls. Methods: Data from PubMed, OVID Technologies, Inc., Cochrane, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scopus, Web of Science, and EMBASE for Excerpta Medica dataBASE (EMBASE) with relevant terms was extracted until December 31, 2020. Inclusion criteria were data of patients with non-syndromic unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP). In the case of UCLP and BCLP, patients with craniofacial syndromes were excluded. The study proposal was registered with PROSPERO (Registration number: CRD42021228632). Results: Fifteen studies with a total of 2032 participants were included for the systematic review and 14 studies with a total of 1972 participants were included for the meta-analysis. The risk of bias was assessed using the Modified Newcastle Ottawa scale under seven domains by two authors. Thirteen studies were graded as "good" and two as "satisfactory." The CBA in patients with CLP were greater than the non CLP Class I controls in six of the 15 studies. CBA was greater in patients with CLP than non-CLP controls by 1.21° (95% CI of 0.19-2.22). Meta-analysis reported considerable heterogeneity (I2 = 86%). Anterior (ACB) and posterior cranial base (PCB) lengths were shorter in patients with CLP than in the non-cleft Class I controls by 2.14 mm (95% CI of 0.99-3.30) and 2.06 mm (95% CI of 1.52-2.60), respectively. Conclusion: Most studies were graded as good. Patients with CLP had greater CBA and shorter ACB and PCB lengths when compared to non-CLP controls.

Timing of Spheno-Occipital Synchondrosis Closure in Cleft Lip and Palate Patients in Iranian Population.

This study aimed to evaluate the chronological age range associated with each stage of spheno-occipital synchondrosis (SOS) fusion in patients with cleft lip and palate compared to the noncleft group, using cone-beam computed tomography (CBCT) images.In this study, the degree of SOS fusion was assessed using a 4-stage scoring system on CBCT images of 190 individuals (92 patients with cleft lip and palate, 98 noncleft individuals). A χ2 test was performed to assess the correlation between age and fusion stage. The independent sample t tests were used to evaluate the differences in the mean values of the samples of each group and each sex, as well as the mean value of each stage (P < .05).The results showed that there was no significant difference in the timing of the SOS fusion stages between the patients with cleft palate and the noncleft group. Although the fusion process of SOS begins about one year earlier in females, the complete ossification occurs at the mean age of 18.5 for both sexes in the experimental group and the mean age of 19.0 in the noncleft group.The present study found no differences in the fusion stages of the spheno-occipital synchondrosis between patients with cleft lip and palate and healthy individuals.

Position of the anterior ethmoidal foramen and trauma to the cranial base during transconjunctival medial orbital decompression: a systematic literature review.

PURPOSE: To review the literature on the location of the anterior ethmoidal foramen (AEF) and trauma during transconjunctival medial wall decompression. METHODS: A comprehensive literature search was conducted using the PubMed, Embase, and Scopus databases, combining the terms "olfactory fossa" and "fovea ethmoidalis" with "trauma," "cerebrospinal fluid leak," "pneumocephalus," "orbital decompression," and "anterior ethmoidal artery" (AEA). All cases of cranial base trauma during medial orbital decompression and the anatomical studies on the location of the AEF and the course of the AEA were reviewed. RESULTS: Ninety-four articles were identified, of which 37 were related to the AEF, 41 reported the course of the AEA, and 16 to reported cases of cranial base trauma. Out of these cases, 10 were related to transconjunctival medial orbital decompression, affecting 11 patients. Most AEFs are situated at the frontoethmoidal suture, but up to 38.15% of AEFs are located above the suture on the frontal bone. Most AEFs are adjacent to the roof of the ethmoidal sinus. The distance of the AEF to the cranial base increases in the presence of supraorbital ethmoidal cells (SOEC). CONCLUSIONS: The position of the AEF is variable and should not be considered a safe landmark for all patients.

Comparative Evaluation of Cranial Base Length and Flexure on Facial Parameters in Hypodivergent, Normodivergent and Hyperdivergent Patients: A Retrospective Cephalometric Study.

AIM: The aim of the study was to assess the influence of cranial base length (CBL) and Flexure on facial parameters in Hypodivergent, Normodivergent, and Hyperdivergent patients. MATERIALS AND METHODS: Around 60 standardized cephalograms were divided into Hypodivergent, Normodivergent, and Hyperdivergent groups (20 each) based on the FMA angle. The CBL, cranial flexure (CF), and various facial parameters were measured for each case. The results were analyzed for the correlation between Cranial and facial parameters in each of the three study groups. RESULTS: Comparison and Pairwise Comparison of variables between study groups were done using ANOVA and Tukey's post hoc Test. Cranial base length, mandibular body length, LAFH, N-Me-Go angle (p-value <0.001), and Jarabak's ratio were found to be significantly different between the groups. Pearson's Correlation showed that most of the facial parameters had a significant correlation with CBL in Hypodivergent groups. CONCLUSION: The CBL is more closely related to facial parameters in vertical dysplasia individuals than CF. The CBL is positively correlated to facial variables, especially in Hypodivergent individuals. The N-Me-Go Angle introduced in the study was significantly different in all three vertical facial types studied; hence, it cannot be used as a valuable diagnostic tool. CLINICAL SIGNIFICANCE: Changes in the length and flexure of the cranial base influence the anteroposterior position of jaw bases. The influence of the cranial base on the development of vertical dysplasias is not studied much, hence the present study aims at resolving this lacuna in literature.

Beyond the beak: Brain size and allometry in avian craniofacial evolution.

Birds exhibit an enormous variety of beak shapes. Such remarkable variation, however, has distracted research from other important aspects of their skull evolution, the nature of which has been little explored. Key aspects of avian skull variation appear to be qualitatively similar to those of mammals, encompassing variation in the degree of cranial vaulting, cranial base flexure, and the proportions and orientations of the occipital and facial regions. The evolution of these traits has been studied intensively in mammals under the Spatial Packing Hypothesis (SPH), an architectural constraint so-called because the general anatomical organization and development of such skull parts makes them evolve predictably in response to changes in relative brain size. Such SPH predictions account for the different appearances of skull configurations across species, either in having longer or shorter faces, and caudally or ventrally oriented occiputs, respectively. This pattern has been morphometrically and experimentally proven in mammals but has not been examined in birds or other tetrapods, and so its generality remains unknown. We explored the SPH in an interspecific sample of birds using three-dimensional geometric morphometrics. Our results show that the dominant trend of evolutionary variation in the skull of crown-group birds can be predicted by the SPH, involving concomitant changes in the face, the cranial vault and the basicranium, and with striking similarities to craniofacial variation among mammals. Although craniofacial variation is significantly affected by allometry, these allometric effects are independent of the influence of the SPH on skull morphology, as are any effects of volumetric encephalization. Our results, therefore, validate the hypothesis that a general architectural constraint underlies skull homoplasy evolution of cranial morphology among avian clades, and possibly between birds and mammals, but they downplay encephalization and allometry as the only factors involved.

Expression of Cre recombinase in chondrocytes causes abnormal craniofacial and skeletal development.

The cranial base synchondroses are growth centers that drive cranial and upper facial growth. The intersphenoid synchondrosis (ISS) and the spheno-occipital synchondrosis (SOS) are two major synchondroses located in the middle of the cranial base and are maintained at early developmental stages to sustain cranial base elongation. In this study, we report unexpected premature ossification of ISS and SOS when Cre recombinase is activated in a chondrocyte-specific manner. We used a Cre transgenic line expressing Aggrecan enhancer-driven, Tetracycline-inducible Cre (ATC), of which expression is controlled by a Col2a1 promoter. Neonatal doxycycline injection or doxycycline diet fed to breeders was used to activate Cre recombinase. The premature ossification of ISS and/or SOS led to a reduction in cranial base length and subsequently a dome-shaped skull. Furthermore, the mice carrying either heterozygous or homozygous conditional deletion of Tsc1 or Fip200 using ATC mice developed similar craniofacial abnormalities, indicating that Cre activity itself but not conditional deletion of Tsc1 or Fip200 gene, is the major contributor of this phenotype. In contrast, the Col2a1-Cre mice carrying Cre expression in both perichondrium and chondrocytes and the mice carrying the conditional deletion of Tsc1 or Fip200 using Col2a1-Cre did not manifest the same skull abnormalities. In addition to the defective craniofacial bone development, our data also showed that the Cre activation in chondrocytes significantly compromised bone acquisition in femur. Our data calls for the consideration of the potential in vivo adverse effects caused by Cre expression in chondrocytes and reinforcement of the importance of including Cre-containing controls to facilitate accurate phenotype interpretation in transgenic research.

Transcranial extradural subtemporal repair for sphenoid sinus lateral recess meningoencephalocele: technical note.

Cranial meningoencephalocele is a rare condition consisting of the herniation of meninges, CSF, and brain tissue through a cranial or skull base defect. Sphenoid sinus lateral recess meningoencephalocele is of particular interest due to the complex anatomy surrounding the bone defect and their demanding surgical management. In this technical note, we reported a step-by-step description of a rare case of sphenoid sinus lateral recess meningoencephalocele causing headache due to recurrent cerebrospinal fluid leak treated with a subtemporal craniotomy with extradural middle cranial fossa drilling and meningoencephalocele removal with multilayer reconstruction. The transcranial route is a safe and effective treatment for sphenoid sinus lateral recess meningoencephalocele repair. The subtemporal extradural approach allows for an optimal exposure of the relevant anatomy minimizing risks and improving the possibility to perform an effective multilayer skull base reconstruction.

Hemangiopericytoma/solitary fibrous tumor of the cranial base: a case series and literature review.

BACKGROUND: Hemangiopericytomas (HPCs) are uncommon soft tissue tumors. HPCs that grow in the cranial base are rare. Therefore, skull-base surgeons tend to overlook this disease. This study aimed to increase the awareness of HPCs by summarizing case data from our institution and related publications. We also aimed to contribute to the number of reported cases for future systematic reviews of HPCs. METHODS: This study included all patients who underwent surgery for HPC/solitary fibrous tumor (SFT) between August 2015 and August 2019. All surgeries were performed at Xiangya Hospital Central South University. We analyzed clinical characteristics, surgical highlights, treatment modalities, and outcomes. RESULTS: We included six patients, aged 32-64 years. Lesions were located in the parapharyngeal space in three patients, pterygopalatine fossa in two, and saddle area in one. All patients underwent nasal endoscopic endonasal surgery. In five patients, tumors involved the internal carotid artery (ICA). The exposure and protection of the ICA during surgery are challenging but critical to complete tumor removal. The 3-year overall survival(OS) rate was 66.7%. CONCLUSIONS: HPC/SFTs are rare tumors of the cranial base that are prone to recurrence. Cranial base HPC/SFTs are often closely associated with the ICA. To our knowledge, this case series reports the largest number of cases of HPCs associated with the ICA. We believe that there is a strong relationship between patient prognosis and whether the tumor encircles the ICA and whether the tumor is completely resected. To confirm this suggestion, more cases are needed for further analysis.

Cranial Base Synchondrosis: Chondrocytes at the Hub.

The cranial base is formed by endochondral ossification and functions as a driver of anteroposterior cranial elongation and overall craniofacial growth. The cranial base contains the synchondroses that are composed of opposite-facing layers of resting, proliferating and hypertrophic chondrocytes with unique developmental origins, both in the neural crest and mesoderm. In humans, premature ossification of the synchondroses causes midfacial hypoplasia, which commonly presents in patients with syndromic craniosynostoses and skeletal Class III malocclusion. Major signaling pathways and transcription factors that regulate the long bone growth plate-PTHrP-Ihh, FGF, Wnt, BMP signaling and Runx2-are also involved in the cranial base synchondrosis. Here, we provide an updated overview of the cranial base synchondrosis and the cell population within, as well as its molecular regulation, and further discuss future research opportunities to understand the unique function of this craniofacial skeletal structure.

Cranial Base Synchondrosis Lacks PTHrP-Expressing Column-Forming Chondrocytes.

The cranial base contains a special type of growth plate termed the synchondrosis, which functions as the growth center of the skull. The synchondrosis is composed of bidirectional opposite-facing layers of resting, proliferating, and hypertrophic chondrocytes, and lacks the secondary ossification center. In long bones, the resting zone of the epiphyseal growth plate houses a population of parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to the formation of columnar chondrocytes. Whether PTHrP+ chondrocytes in the synchondrosis possess similar functions remains undefined. Using Pthrp-mCherry knock-in mice, we found that PTHrP+ chondrocytes predominantly occupied the lateral wedge-shaped area of the synchondrosis, unlike those in the femoral growth plate that reside in the resting zone within the epiphysis. In vivo cell-lineage analyses using a tamoxifen-inducible Pthrp-creER line revealed that PTHrP+ chondrocytes failed to establish columnar chondrocytes in the synchondrosis. Therefore, PTHrP+ chondrocytes in the synchondrosis do not possess column-forming capabilities, unlike those in the resting zone of the long bone growth plate. These findings support the importance of the secondary ossification center within the long bone epiphysis in establishing the stem cell niche for PTHrP+ chondrocytes, the absence of which may explain the lack of column-forming capabilities of PTHrP+ chondrocytes in the cranial base synchondrosis.

Defining the critical period of hedgehog pathway inhibitor-induced cranial base dysplasia in mice.

BACKGROUND: The hedgehog signaling pathway is critical for developmental patterning of the limb, craniofacial and axial skeleton. Disruption of this pathway in mice leads to a series of structural malformations, but the exact role and critical period of the Hh pathway in the early development of the cranial base have been rarely described. RESULTS: Embryos exposed to vismodegib from E7.5, E9.5, and E10.5 had a higher percentage of cranial base fenestra. The peak incidence of hypoplasia in sphenoid winglets and severe craniosynostosis in cranial base synchondroses was observed when vismodegib was administered between E9.5 and E10.5. Cranial base craniosynostosis results from accelerating terminal differentiation of chondrocytes and premature osteogenesis. CONCLUSIONS: We define the critical periods for the induction of cranial base deformity by vismodegib administration at a meticulous temporal resolution. Our findings suggest that the Hh pathway may play a vital role in the early development of the cranial base. This research also establishes a novel and easy-to-establish mouse model of synostosis in the cranial base using a commercially available pathway-selective inhibitor.

Cell lineage- and expression-based inference of the roles of forkhead box transcription factor Foxc2 in craniofacial development.

BACKGROUND: Foxc2 is a member of the winged helix/forkhead (Fox) box family of transcription factors. Loss of function of Foxc2 causes craniofacial abnormalities such as cleft palate and deformed cranial base, but its role during craniofacial development remains to be elucidated. RESULTS: The contributions of Foxc2-positive and its descendant cells to the craniofacial structure at E18.5 were examined using a tamoxifen-inducible Cre driver mouse (Foxc2-CreERT2) crossed with the R26R-LacZ reporter mouse. Foxc2 expression at E8.5 is restricted to the cranial mesenchyme, contributing to specific components including the cranial base, sensory capsule, tongue, upper incisor, and middle ear. Expression at E10.5 was still positively regulated in most of those regions. In situ hybridization analysis of Foxc2 and its closely related gene, Foxc1, revealed that expression domains of these genes largely overlap in the cephalic mesenchyme. Meanwhile, the tongue expressed Foxc2 but not Foxc1, and its development was affected by the neural crest-specific deletion of Foxc2 in mice (Wnt1-Cre; Foxc2fl/fl ). CONCLUSIONS: Foxc2 is expressed in cranial mesenchyme that contributes to specific craniofacial tissue components from an early stage, and it seems to be involved in their development in cooperation with Foxc1. Foxc2 also has its own role in tongue development.

Intraorbital and intracranial extension of adenoid cystic carcinoma without clinical or radiological lacrimal gland involvement.

Adenoid cystic carcinoma (AdCC) is a rare epithelial neoplasm of the head and neck, most commonly found in the salivary glands. Orbital AdCC is an uncommon clinical entity arising from the lacrimal glands, however primary orbital AdCC has been previously described in a small number of case reports. The exact origin of the neoplasm with uninvolved lacrimal gland in the orbit is unknown, however it may arise from ectopic lacrimal or salivary gland tissue, or extension from nearby epithelial structures. We describe the clinical characteristics, investigations and management of a 55-year-old man presenting with vertical diplopia, found to have left posterior orbital AdCC invading the skull base with intracranial extension involving the inferotemporal fossa, pterygopalatine fossa, left carotid artery, cavernous sinus and temporal lobe dura, without clinical or radiological lacrimal gland involvement or systemic metastases.

Ontogeny of cranial base during the first two years of life.

The integration of the growth of the brain and the cranial base suggests that each system may influence the other, notably during the first three years of life, although this influence has never been proven to be exclusive. The aim of our work was to analyse the dynamics of normal growth on the one hand, and the development and ontogenetic allometry of the cranial base in the infant on the other hand. MATERIAL AND METHOD: A total of 32 infants (17 males/15 femeles) having been included in the unexpected infant death french protocol were analyzed. Three-dimensional reconstructions of the cranial base were performed from CT scans. The technique combined manual segmentation of regions of interest, contour extraction and surface reconstruction. Nineteen landmarks were positioned on each of the bone surfaces. RESULTS: No correlation was observed between sex assigned at birth and shape, weight, crown-heel length, or head circumference. Principal component analysis showed that 85.5% of the variance observed on the first component was secondary to growth. After Procrustes superimposition, 25% of the shape variance observed was explained by the first principal component. It showed anteroposterior lengthening of the cranial base. In addition, the height, width and length of the posterior fossa increased and the relative position of the basion was displaced inferiorly and anteriorly with flexion of the sphenoid angle. Negative allometry was also observed. CONCLUSION: Our study, carried out in a rigorously selected population of infants, presents a fundamental approach to ontogeny through study of shape, growth and ontogenetic allometry.