Skull Base Embryology: a Multidisciplinary Review

Childs Nerv Syst (2014) 30:991–1000 DOI 10.1007/s00381-014-2411-x

REVIEW PAPER

Skull base embryology: a multidisciplinary review

Antonio Di Ieva & Emiliano Bruner & Thomas Haider & Luigi F. Rodella & John M. Lee & Michael D. Cusimano & Manfred Tschabitscher

Received: 11 March 2014 /Accepted: 25 March 2014 /Published online: 17 April 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract promises to expand our knowledge and enhance our ability to Introduction The skull base represents a central and complex treat associated anomalies. bone structure of the skull and forms the floor of the cranial cavity on which the brain lies. Anatomical knowledge of this Keywords Anatomy . Comparative anatomy . Embryology . particular region is important for understanding several path- Skull base . Encephalocele . Pharyngeal arches . Functional ologic conditions as well as for planning surgical procedures. craniology Embryology of the cranial base is of great interest due to its pronounced impact on the development of adjacent regions including the brain, neck, and craniofacial skeleton. Introduction Materials and methods Information from human and comparative anatomy, anthropology, embryology, surgery, and com- The skull base represents a central and complex bone structure puted modelling was integrated to provide a perspective to of the skull and forms the floor of the cranial cavity on which interpret skull base formation and variability within the cranial the brain lies. Nerves and blood vessels cross skull base functional and structural system. foramina while the foramen magnum allows anatomical con- Results and conclusions The skull base undergoes an elabo- tinuation between the spinal cord and the brain. Anatomical rate sequence of development stages and represents a key knowledge of this particular region is important for under- player in skull, face and brain development. Furthering our standing several pathologic conditions as well as for planning holistic understanding of the embryology of the skull base surgical procedures. Embryology of the cranial base is of great interest due to its pronounced impact on the development of : A. Di Ieva (*) M. D. Cusimano adjacent regions including the brain, neck and craniofacial Division of Neurosurgery, Department of Surgery, St. Michael’s skeleton [1–9]. Hospital, University of Toronto, 30 Bond Street, Toronto, ON, Canada M5B 1W8 e-mail: [email protected] Anatomical synopsis of the skull base A. Di Ieva : T. Haider : M. Tschabitscher Centre for Anatomy and Cell Biology, Department of Systematic Figure 1 shows the intracranial and exocranial surfaces of the Anatomy, Medical University of Vienna, Vienna, Austria skull base. The intracranial portion of the skull base can be E. Bruner divided into three parts: the anterior, the middle and the Centro Nacional de Investigación sobre la Evolución Humana, posterior cranial fossa. Two paired frontal bones, the sphenoid Burgos, Spain and ethmoid bone give rise to the anterior cranial fossa bearing L. F. Rodella : M. Tschabitscher the ventral part of the frontal lobe (orbital gyri). The frontal Department of Clinical and Experimental Sciences, University of bone originates from two symmetric bones after fusion of the Brescia, Brescia, Italy metopic suture forming the main portion of this fossa and the roof of both orbits [10]. The cribriform plate of the ethmoid J. M. Lee Department of Otolaryngology-Head and Neck Surgery, St. bone is located between the two frontal bones and Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada allows connection between the olfactory filiae and the nasal 992 Childs Nerv Syst (2014) 30:991–1000

abducens nerve runs upwards to the cavernous sinus. After its extradural course the sixth nerve first enters the sphenopetroclival venous gulf to reach Dorello’s canal located below the ligament of Gruber and finally passes through the cavernous sinus. [14]. The posterior fossa is bounded laterally by the temporal and the occipital bone and behind and above by the parietal bone. It is the largest cranial fossa and contains the cerebellum, pons and medulla oblongata and allows connection to the cervical spinal cord through the foramen magnum [15]. Further important foramina within this fossa are the internal acoustic canal, the vestibular aqueduct and the jugular foramen containing the glossopharyngeal, the vagus and the accessory nerve as well as the internal jugular vein [15, 16]. Fig. 1 Intracranial (left) and exocranial (right) surfaces of the mature The inferior (exocranial) surface of the skull base is not skull base divided in three compartments and needs to be described separately. Besides the largest portion, the palatine process of the maxilla, the zygomatic process of the maxilla and the cavity. Anteriorly, the ethmoid bone also comprises the crista palatine bone represent the anterior external part. The middle galli, an anchor for the falx cerebri. While the lesser wing of part of the cranial base comprises the body of the sphenoid, the sphenoid bone marks the dorsal boundary of the anterior the petrous part of temporal bones and the basiocciput and cranial fossa, the body and greater wing represent the ventral extends to a virtual transverse line dividing the foramen mag- and lateral part of the middle cranial fossa. Also the squamous num. The bones of the posterior part of the external skull base part of the temporal bone and the parietal bone form the lateral correspond with the intracranial posterior cranial fossa with its border of the middle fossa. In the middle of this fossa, a prominent occipital bone. Most prominent structures are the prominent concave structure is arranged, the sella turcica, foramen magnum and the occipital condyles connecting the containing the hypophysis and building the roof of the sphe- skull to the cervical spine [15]. Variants of occipital condyles noidal sinus. The cavernous sinus is located to both sides of have been described, such as appearance of a third condyle the sella, comprising important structures. The internal carotid with occasional articulation with the dens axis, and a rare artery passes through the cavernous sinus in an S-shaped variant of duplicated occipital condyles [2, 17–19]. manner forming the so-called carotid siphon. Branches from this part of the internal carotid artery supply the hypophysis, part of the dura mater, the optic chiasm, the sixth nerve and the Embryologic aspect of the skull base trigeminal ganglion [11]. Also the abducens nerve proceeds straight through the cavernous sinus, while the maxillary, Pharyngeal arches ophthalmic, trochlear and oculomotor nerves run within the lateral wall [12]. The maxillary nerve originates from the Development of the vertebrate head require the formation of trigeminal ganglion (ganglion Gasseri) where the nerve breaks the neural crest, which represents the origin for connective and down into its three branches, the ophthalmic, the maxillary skeletal tissue of the neck, face and skull [8]. In contrast to and the mandibular nerve located within a duplication of dura trunk neural crest cells, cranial neural crest cells migrate called trigeminal or Meckel’s cave. Foramina in the middle before neural folds fuse to form the neural tube, which is not cranial fossa allow passage towards the viscerocranium, the case for the cranial crest in non-mammalian vertebrates [8, namely the superior orbital fissure for the ophthalmic nerve, 20]. The rostral population of neural crest cells is the major the foramen rotundum for the maxillary nerve and the foramen contributor to skull formation being the origin of the whole ovale for the mandibular nerve. A variant “oval canal” has viscerocranium and the rostral part of the neurocranium [8, 9]. been described, where an osseous lamina continuous with the In adolescents, the coronal suture between the frontal and the pterygoid plate canopies the foramen ovale [13]. The temporal parietal bones marks the boundary between neural crest and lobe is located within the middle cranial fossa supporting its cranial mesoderm origin [10, 20]. Gradual migration of neural distinct shape. The posterior aspect of the sella turcica, the crest cells around the embryonic pharynx leads to formation of dorsum sellae, the posterior part of the sphenoid bone and the five pairs of embryonic arches, each containing epithelial basilar part of the occipital bone represent the anterior border covered ecto- and endoderm as well as mesenchyme originat- of the posterior cranial fossa. Both also contribute to the ing mainly from the neural crest. Neural crest cells of the first formation of the clivus, a sloped bone structure on which the two arches contribute to cranial skeletal elements with Childs Nerv Syst (2014) 30:991–1000 993 associated connective tissue. Condensation of neural crest- base foramina before bones are formed [8]. Defective devel- derived mesenchyme leads to sub-sequential chondrification. opment of the cranial base has been described to be associated After completion of chondrogenesis, dorsal extension con- with anencephaly underlining its importance in development tinues until it reaches the cranial base located laterally to the of the whole skull and brain [4]. The rostral tip of the noto- hindbrain. Arch cartilage undergoes endochondral ossifica- chord (chorda dorsalis) reaches a location caudal to the hy- tion, ligamentous ossification, and a combination of both or pophysis and represents the start of the development of the remains cartilage [8]. Most parts of the skull vault and face cranial base. This part of the notochord is rich in sulphated undergo intramembranous ossification through mesenchymal glycosaminoglycans inducing condensation and chon- condensation while endochondral ossification of the skull drification of adjacent occipital sclerotome-derived base is predominant [8, 9, 15, 21]. mesenchemye. This leads to the formation of the parachordal Figure 2 shows the cranial view of the skull base during cartilage, which by week 7 forms the basioccipital element of 12th week of fetal development. the occipital bone and therefore the occipital part of the foramen magnum. Before reaching the prechordal plate, the Chondrocranium notochord makes contact with the endoderm of the primitive pharynx followed by formation of the pharyngeal The first skeletal structures to differentiate are cartilages of the (Tornwaldt’s) bursa [29–31]. Its possible relationship to the skull base, the sensory capsules, the viscerocranium and the adjacent variable fossa navicularis has been described previ- occipital bone. Development of the cranial base is regulated ously [29]. Exooccipital components chondrify thereafter and by a variety of genes like genes from the Dickkopf family, build the rostral boundary of the foramen magnum. Deduced matrix metallopeptidase 9, Indian hedgehog and Sonic hedge- from the observation on somitic contribution to its develop- hog (Shh) [22–26]. It has been stated that skull base chondro- ment it is believed that the occipital bone represents a vertebral genesis compared to chondrogenesis of the axial skeleton is element that has expanded to support the brain [25, 27, 28, delayed during embryological development due to its unre- 32–34]. Variant forms of occipital condyles have been de- sponsiveness to Shh signaling [25]. Both mesoderm and ec- scribed as mentioned before. Hayek proposed in 1924 that a toderm represent tissue origins for the development of the tertiary condyle is the result of incomplete regression of the cranial base [8, 25, 27]. Neural crest derived cells contribute proatlas, a hypochordal plate needed for proper development to development of parts anterior to the notochord while the of the occipital bone and its condyles and usually disappears posterior skull base originates from mesoderm [8, 25, 27, 28]. during development [35, 36]. Variant proatlas development Interestingly, cartilage development through mesenchymal can furthermore lead to hypoplastic condyles and occipital condensation takes place after cranial nerves and blood ves- encephaloceles causing problems in the craniovertebral junc- sels have developed resulting in a specific location of skull tion [36, 37] Below the occipital bone, deficient differentiation

Fig. 2 Cranial view of the skull base during 12th week of fetal Supraoccipital cartilage development Foramen magnum

Jugular foramen Occipital bone Hypoglossal canal

Internal auditory meatus Meckel`s cartilage Trigeminal passage Dorsum sellae Carotid foramen

Sup. orbital fisssure Parietal cartilage Optic canal Sphenoid bone

Cribriform plate Frontal cartilage

Ethmoid bone Nasal bone 994 Childs Nerv Syst (2014) 30:991–1000 can lead to ossification of the atlanto–occipital joint, a so- apoptosis are important during the final process of skull de- called “occipitalization” of the atlas bone [38, 39]. Also intra- velopment and were shown to be regulated mainly by MMP-9 cranial manifestation of the atlas has been described, where a and genes from the Dickkopf (Dkk) family [22]. During week prominent structure broadens the margin of the foramen mag- 5 of embryological development, ossification is initiated [44]. num [40]. Between the parachordal and the exooccipital car- Various results considering the location of initiation of ossifi- tilages, roots of the hypoglossal nerve are localized leading to cation have been reported ranging from the region surround- the hypoglossal canal after fusion. Rostrally, ongoing differ- ing the Rathke’s pouch to areas tangent to neural structures entiation leads to development of the hypophysial cartilages such as nerves [21, 44, 45]. Bilateral symmetry of ossification located on each side of the hypophysial pouch followed by is regulated by the centrally localized chordal cartilage pro- merging of the median plane to form the primordium of the ducing chordin, a regulator of bone morphogenetic protein 7 postsphenoid around the hypophysial stalk. During formation (BMP-7) [21]. In rare cases, fibrous dysplasia alters ossifica- of skull base cartilage, the adenohypophysial pouch remains tion of the skull resulting in replacement of the bone structure connected to the roof of the oral cavity (Rathke’spouch)until with fibrous tissue [46, 47]. further differentiation leads to closure and the formation of the Because of its central position and regulation of adjacent sella turcica with its hypophysial fossa [15]. In rare cases this differentiation during ongoing craniofacial development, perforation persists, leading to formation of the malformations like craniosynostosis will most commonly craniopharyngeal canal [41, 42]. The presphenoid cartilages, manifest within the spheno-occipital synchondrosis [48]. the cartilaginous basis for the jugum of the sphenoid body, Physiologically, this synchondrosis closes between the age differentiate last within the medial aspect of the cranial base of 13 and 18 [49]. and bridge the gap between the postsphenoid and the cartilaginous nasal capsule, which is already well developed by the third month of fetal development. A transient opening in the anterior skull base anterior to the crista galli, the foramen The skull base in vertebrates cecum, allows dura to pass through toward the prenasal space located inferoposterior to the nasal bones and anterosuperior The cranial base has important integrative and functional roles to the nasal cartilage. A temporary fontanelle, the fonticulus in the skull, many of which reflect its phylogenetic history frontalis, divides the inferior frontal bone from nasal bone [50]. The shape of the cranial base is therefore a multifactorial [43].Thesetransitoryspaces(foramencecum,prenasalspace product of numerous phylogenetic, developmental, and func- and fonticulus frontalis) regress during physiological devel- tional interactions. opment. Incomplete involution cause different pathologies as In their New Head Hypothesis (NHH), Gans and Northcutt discussed later in this article. The nasal conchae ossify during [51] proposed that vertebrates evolved by adding a “new the fifth month and become part of the ethmoid bone (superi- head” rostral to the notochord, made of ectodermally derived or/middle concha) or form a separate bone (inferior concha), sense organs and nervous structures, to aid in predatory be- while the ossification of lateral parts of the nasal capsule haviour. Subsequent work described this building of a new creates the orbital plate and the ethmoidal labyrinth. The rest head as including, among other things, an “anterior extension of the nasal capsule undergoes intramembranous ossification of the connective tissues providing a connection among the (vomer, nasal bones) or remains cartilaginous (septum, alae) sensory capsules” and specifically posited that these rostral [8, 15]. Ossification of the orbit excludes the most rostral part, connective tissues are neomorphic, developing from neural- which forms a cartilaginous bridge to become continuous with crest derived mesenchyme. The NHH predicts that the the presphenoid cartilage representing the caudal boundary of prechordal–chordal boundary should be coincident with the the optic foramen and consequently enclosing the optic nerve. neural crest–mesoderm boundary and that connective tissues Later, this bridge ossifies and becomes the lesser wing of the of the prechordal head, including bone and cartilage, should sphenoid bone. Around the otocyst, mesenchymal condensa- be derived from the neural crest. So far, the skeletal and tion leads to formation of the cochlea and semicircular canals connective tissues of the rostral cranium, from fishes to mam- followed by chondrogenesis around the vestibulocochlear malian, have been shown to be derived from the neural crest nerve to create the internal acoustic meatus. Adjacent chon- while cranial muscles are derived from prechordal and cephal- drogenesis around the carotid arteries forms the carotid canals. ic paraxial mesoderm [52, 53]. Anatomically, the cranial base Passage of the jugular vein is sustained by differentiation of represents the most inferior area of the skull, composed of the parachordal cartilage around the vein to build up the jugular endocranium and lower parts of the skull roof. The foramen [8, 15, 21]. endocranium shows several differences among different clas- Ongoing chondrogenesis of mesenchyme connects sepa- ses of animals. We generally observe a reduction in the num- rate cartilages and forms a continuous framework after ber of bones that constitute the skull base. This reduction is 9 weeks of fetal development [15]. Skeletogenesis and accompanied by a specialization of maxillofacial skeleton. Childs Nerv Syst (2014) 30:991–1000 995

The endocranium of fishes is composed of the neuro- in the basioccipital, except for its anterolateral and posterolat- cranium, the jaws (or mandibular arch), the hyoid arch eral corners. The jugular foramina are large, formed between and the branchial arches. In some fishes, like jawless fish and the exoccipital and opisthotic, and on their concave sharks, the endocranium is cartilaginous (Chondrichthyes), posteromedial borders, a pair of small foramina are present. with both the upper and lower jaws being separate elements. These are confluent with the condylar canal for the passage of In other fishes (Osteichthyes), the endocranium is ossified. As the hypoglossal nerves. the name implies, the endocranium encases the brain and In birds, the cranial base extends caudal to the optic nerve further houses nerves and blood vessels. The neurocranium and includes basioccipital and pre-sphenoid bones which de- also contains the paired sensory organs: paired nasal capsules rive from mesoderm. It has different lengths among birds at the anterior, paired orbital capsules (or eye) behind those resulting in neurocranial differences [55]. The ventral convex- and paired otic (or ear) capsules posterior to the orbital ity of the cranial base in avians would be topologically equiv- capsules. alent to the retroflexion of the rats cranial base. Moreover, the In amphibians, of the 11 bones comprising the anterior portion of the avian cranial base does not ossify in neurocranium, only four, the parasphenoid, the basioccipital, many avians, whereas in mammals this region of the cranial the paired epipterygoids and the stapes, are distinct and un- base is always ossified. There is a recent hypothesis of an fused [53]. The other bones, however, are inseparably united additional bone, namely the intra-parietal located between to others to form two larger bony units, which are delimited by the parietal and the supraoccipital bones. Birds with greater flight sutures externally, but are confluent on their endocranial faces. mobility have a much more rounded cranial architecture [56]. The lateral sphenoids, which had not been recognized previ- The endocranium in mammals is reduced in relative size ously, are evident as plates, which extend from the and number of bones compared to the condition in the ances- basisphenoid region to the roof of the skull, and from the tral land vertebrates [8]. The mouse has became a popular trigeminal nerve foramina to the rostral part of the basi- model organism for studies of craniofacial development. In sphenoid (optic nerve region). The other mass of bone is adult mice the cranial base is composed of the ethmoid, placed posteriorly and consists of the exoccipitals, presphenoid, basisphenoid and basioccipital bones along with paroccipitals, prootics and the supraoccipital. These elements the auditory capsules of the temporal bones. In mammals, all house the internal ear and cover the upper and lateral parts of four occipital elements typically fuse to form a single occipital the brain stem. Save for the exoccipital, whose external limits bone. are marked by suture lines, these elements are fused entirely to one another. The skull base in anthropology and functional craniology Reptilian skull base is similar to that of mammals and includes the ethmoid, the sphenoid, the temporal and the Cranial base has been always a major topic in anthropology occipital bones. Reptiles possess an extensively chondrified and evolution. In his famous book, Evidence as to Man’sPlace endocranium composed of parachordal cartilage and broad in Nature (1863), Thomas Henry Huxley [57] introduced the orbital cartilage that directly surrounds the neural tube [54]. importance of the cranial base suggesting pioneering geomet- The basisphenoid and parasphenoid are fused, except at the ric models to investigate the differences among human popu- anterior end of the basisphenoid dorsally, where a slight lations (Fig. 3). Because of its role as interface between vault, separation is present in the region of the trabecular attachment face, and body, the cranial base morphology has always to the basisphenoid. The tip of the cultriform process of the represented a debated issue in evolutionary biology. Despite parasphenoid is sutured anteriorly to the pterygoids, and the the attention dedicated to its anatomy and variations, few process extends posteriorly between the interpterygoid vacu- agreements have been achieved concerning its role in human ities. At this point the cultriform process bears a ventral keel, evolution, mostly because of its complex structure and multi- and in the region between the prominent internal carotid ple functional factors involved in its morphology. The limited foramina, it expands and bears five small teeth on a roughened information we have also on the current human populations area. From this area, the wings of the parasphenoid expand for many epigenetic traits like sutures, foramina, and anatom- and pass back over the basioccipital in a squamous suture, the ical variants of the endocranial characters, further hampers a full extent of which is obscured by breakage. There is a small proper knowledge of the cranial base dynamics [58]. gap between the basioccipital and basisphenoid (known as The cranial base anatomy is a major determinant of the unossified region), which was undoubtedly filled with carti- cranial architecture in primates, and a major constrain of the lage. The basioccipital is a hexagonal bone and bears paired overall cranial form [7, 59]. During human evolution, cranial oval depressions on the ventral surface. The otic region shows base morphology has been deeply influenced by both facial a fenestra ovalis. Posteriorly, the fenestra ovalis is confluent and brain variations [60, 61]. The flexion of the cranial base with the jugular foramen. Anterior to the fenestra ovalis, a has been hypothesized to be a relevant factor in the deep recess is present in the skull base. It is formed principally encephalization process associated with human evolution, 996 Childs Nerv Syst (2014) 30:991–1000

hypothesized that dismorphologies and craniosynostosis are actually the result of morphogenetic imbalance between the cranial base and such connective tensors [69]. The constraints associated with the cranial base produced some co-evolution between its traits and characters, and it has been hence interpreted as an evolutionary anatomical unit [70]. Nonetheless, because of the multifactorial influences, at evolutionary and ontogenetic levels, in functions as well as in structural relationships, the cranial base cannot be regarded as an integrated morphological unit. As a matter of fact, at least considering the modern human variation, the three endocranial fossae display a scarce reciprocal integration in terms of morphology [71]. Similarly, the midsagittal elements display a scarce integration with the lateral elements [72]. Such limited integration within the components of the cranial base is the result of the multiple and independent influences of the other cranial districts on the morphology of the cranial fossae. Low integration practically means that every part has a relatively independent morphogenesis and common patterns influencing the whole cranial base are weak. Thus, the morphology of a specific area of the cranial base is not informative on the possible morphology of other areas, because its morphogenesis is not channelled through few global processes, but rather moulded by many local influences. The anterior fossa is strongly constrained by the orbital and upper face structures [66, 73, 74]. The morphology of the middle fossa is associated with the mandibular anatomy and biomechanics [72]. The posterior fossa is sensitive to the Fig. 3 In 1863, Thomas Huxley demonstrated the importance of the parieto–occipital integration schemes and by the cerebro- cranial base as major determinant of the cranial architecture. He used cerebellar dynamics [75, 76]. Apart from these specific cranial geometrical models and cranial base superimposition to compare human groups, stressing that future development of these techniques will be interactions, the cranial base is also largely influenced by other necessary to understand the complex organization of the cranial anatomy functional components like speech (phonation system) or posture (head position and balancing). This multifactorial system, in terms of evolutionary patterns, has generated mo- because of its role in spatial packing of the brain mass. saic changes in the different hominid lineages, instead of Nonetheless, there are major disagreements in this sense, linear, homogeneous, or gradual variations [77]. mostly because of difficulties in quantitative and comparative As predicted by Huxley, biostatistics has now developed approaches when dealing with homology and anatomical further his geometrical models by using computer science references [62, 63]. In terms of ontogenetic changes, the both to investigate anatomy (digital anatomy and biomedical flexion of the cranial base is almost completed at the second imaging) and to analyze its variation (geometric morphomet- year [64]. However, the morphogenesis of this area is ex- rics) [78]. Such techniques have been soon applied to evaluate tremely complex, not linear, and formed by stages of flexion cranial integration in ontogeny and evolution [79]. In shape and retro-flexion [6, 65]. Such morphogenetic complexity analysis, geometric coordinates are superimposed as to mini- generates operational problems in terms of developing com- mize shape differences, and then the correlation between the parative studies among primates. coordinate variation is analyzed through multivariate statistics An important biomechanical interaction within the face is and functions for spatial interpolation [80–82]. If we analyze represented by the ethmo–maxillary complex [66]. The cranial the endocranial base in adult humans by this way, we can base matures earlier than the facial block, and in this sense it recognize and quantify the underlying relationships associated constraints the following splanchnocranial morphogenesis with the observed morphological variability (Fig. 4)[71]. As [67]. On the other hand, the structural relationships between mentioned, the morphological integration of the endocranial endocranial base and vault are probably influenced by the base is poor and there are no strong correlation patterns redistribution of growth forces exerted by meningeal tensors characterizing the overall phenotypic differences. However, like the falx cerebri and tentorium cerebelli [68]. It has been the structure of the shape variation displays two main patterns, Childs Nerv Syst (2014) 30:991–1000 997 which, despite their limited strength, must be intended as the The limited integration involves also a scarce influence of principal vectors of variability. Considering the endocranial size: in adults, dimensions have a limited influence on view in two dimensions, the first component is associated with endocranial shape. Males are generally larger than females, widening and enlargement of the temples and shortening of and sexual differences are generally related to this minor the posterior fossa. The second component is associated with allometric component: men use to have relatively shorter antero-posterior shortening of the temples and lengthening of anterior fossa and longer and taller sphenoid. It is worth noting the middle fossa. In lateral projection, the first component is that in all these analyses the median elements (foramina, sella, associated with flexion of the cranial base, stretching of the petrous apex) display a remarkable stability in their spatial sphenoid and shortening of the posterior fossa. The second position. component is associated with flattening of the cranial base and stretching of the sphenoid. If we analyze the whole structure in three dimensions, the first component Skull base embryology: clinical implications for congenital is associated with narrowing and heightening of the defects of the anterior skull base endocranial base, while the second component is linked to reduction of the posterior fossa with heightening and Congenital defects of the skull base are rare anomalies that can flexion of the cranial base. Of the whole transformation, result from altered embryogenesis and has significant clinical these two 3D components explain 15 % and 12 % respec- implications in the pediatric population. As it has been tively. Hence, together they account only for the 27 % discussed in this paper, formation of the skull base and facial of the variability, while the rest of the variance associ- skeleton results from a complex interaction of cellular prolif- ated with other minor scattered patterns. eration and regression involving migration of neural crest cells

Fig. 4 The endocranial variation in adult humans can be analysed by using a system of geometric coordinates to evidence the main spatial patterns generating the phenotypic variability. Color maps show such patterns (PC1 and PC2: first and second principal components of variation) in upper and lateral 2D projections, on deformation grids based on a thin-plate spline interpolation functions (red: dilation; blues: compression). Wireframes show the same patterns in 3D (upper and lateral views), and the mean differences between males (blue links)and females. Models have been symmetrized. Data after Bruner and Ripani [71] computed with PAST 2.14 (http://nhm2.uio.no/ norlex/past/download.html), and MorphoJ 1.05f (http://www. flywings.org.uk/MorphoJ_guide/ frameset.htm?changelog.htm) 998 Childs Nerv Syst (2014) 30:991–1000 through ectodermal and mesodermal derived structures. all encephaloceles involves removing the herniated brain tis- Anteriorly, as the frontal bone, nasal bone, ethmoid bone sue and reconstructing the bony defect. Ultimately, this re- and nasal capsule fuse, potential spaces are created which quires an intimate knowledge of the embryologic origins of normally regress by birth. Persistence of these spaces includ- the skull base anatomy. ing the fonticulus nasofrontalis (region between frontal and nasal bones), pre-nasal space (region between nasal bones and nasal capsule) and the foramen cecum (region between frontal Conclusion and ethmoid bone) may lead to the herniation of intracranial contents or glial tissue forming either encephaloceles or glio- Being one of the most complex bones known, the skull base mas. Alternatively, ectodermal and mesodermal tissue may be undergoes an elaborate sequence of development stages and entrapped in these spaces, which lead to the formation of represents a key player in skull, face and brain development as dermoids. discussed in this review paper. Achieving its distinct form was From a clinical standpoint, dermoids are the most common obligatory in human evolution allowing encephalisation and midline congenital nasal mass and can present as a non- brain augmentation. Its intricate anatomical properties togeth- pulsatile cyst, sinus or fistula on the external nose. Because er with the extensive interplay during embryologic develop- of its embryologic origins, 30 % of dermoids can communi- ment with adjacent regions pose a great challenge for holistic cate with the dura and proper imaging is required to determine understanding of the skull base. Rapidly increasing knowl- their exact attachment site. On the other hand, gliomas repre- edge of its embryological development formed the corner- sent herniated glial tissue along the skull base and facial stone of understanding different skull base pathologies and skeleton fusion planes but do not have any communication its underlying pathophysiology, ultimately improving surgical with the cerebrospinal fluid (CSF). As such, they also present treatment. clinically as non-pulsatile masses and can be either extranasal (60 %), intranasal (30 %), or combined (10 %). Furthermore, up to 15 % of gliomas can have attachments to the dura [83]. Encephaloceles are by definition a herniation of brain tissue that maintains a connection to the subarachnoid space References that contains CSF. If the tissue also contains meninges, they are referred to as meningoencephaloceles. Traditionally, 1. Ross C, Henneberg M (1995) Basicranial flexion, relative brain size, encephaloceles have been classified as being either occipital, and facial kyphosis in Homo sapiens and some fossil hominids. Am J sincipital, or basal [84]. In North America and Europe, occip- Phys Anthropol 98:575–593 2. Tubbs RS, Salter EG, Oakes WJ (2005) Duplication of the occipital ital encephaloceles are the most common and are often asso- condyles. Clin Anat 18:92–95 ciated with other congenital disorders. They can vary in size 3. Ross CF, Ravosa MJ (1993) Basicranial flexion, relative brain size, but can be large enough to involve the foramen magnum and and facial kyphosis in nonhuman primates. Am J Phys Anthropol 91: be associated with microcephaly. Sincipital encephaloceles 305–324 4. Lomholt JF, Fischer-Hansen B, Keeling JW, Reintoft I, Kjaer I (2004) refer to encephaloceles which are visible on the face. They Subclassification of anencephalic human fetuses according to mor- occur either at or anterior to the foramen cecum, a small phology of the posterior cranial fossa. Pediatr Dev Pathol 7:601–606 foramina located in the frontal–ethmoidal suture between the 5. Jeffery N (2005) Cranial base angulation and growth of the human frontal bone and the crista galli of the ethmoid bone [85]. fetal pharynx. Anat Rec A: Discov Mol Cell Evol Biol 284:491–499 6. Jeffery N, Spoor F (2002) Brain size and the human cranial base: a These malformations typically extend to the facial skeleton prenatal perspective. 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