Craniofacial embryology and postnatal development of relevant parts of the upper respiratory system.

OBJECTIVES: To compare historical and current knowledge relating to the development of the paranasal sinuses, the nose and face, the Eustachian tube and temporal bones, particularly with respect to chronic inflammation during childhood. METHODOLOGY: Traditional literature data, mainly emanating from text books, were supplemented with information based on a non-structured PubMed search covering the last two decades. RESULTS: Historical knowledge has most often been confirmed, sometimes supplemented and only rarely challenged by present-day studies. Recent studies focus mainly on the clinical application of modern imaging techniques. CONCLUSIONS: Interest in the development of relevant parts of the upper respiratory system remains as lively as ever. Imaging techniques with low or absent radiation exposure may give rise to a novel field of research, especially with respect to paediatric rhinosinusitis.

The Comparison of the Right and Left Sigmoid Sinus Cross-Sectional Areas in Fetal Period and the Factors Affecting the Venous Dominance.

OBJECTIVES: Skull base is an important and a challenging area for surgeons. Success in skull base surgery depends on various factors such as pre-operative evaluation, appropriate surgical technique, anesthesia duration, intraoperative neuromonitorization and wound care. MATERIALS AND METHODS: This study was performed in the Anatomy dissection laboratory of M.U. Medical Faculty (Ethical committee approval number 2010-103). Twelve fetuses between 17-33 gestational weeks fixed with formaldehyde were enrolled to the study. RESULTS: This study was planned to investigate the cross sectional areas of the sigmoid sinus in three levels to compare the right-left sides and the probable relationship among the levels in fetuses to further delineate the developmental factors on jugular foramen asymmetry. The cross-sectional measurements of sigmoid sinus lumen were done on 3 levels which are described as A1 level; sinodural angle, A2 level; the midpoint between the sinodural angle and endocranial orifice and A3 level as the entrance (endo-cranial orifice) of the jugular foramen. There is a strong positive correlation between left (L) A1 and L A2 and also the same for L A1 and right (R) A2. These strong and positive correlations are all valid between L A2-L A3, L A2-R A2, L A2-R A3, L A3-R A3, R A1-R A2. CONCLUSION: Multicenter studies would be beneficial to investigate the topic with greater number of fetuses also on the different regions for genetic differences.

Mesencephalic innervation of the vibrissal follicle-sinus complex in the mouse embryo.

Peripheral projections of neurones whose cell bodies lie in the mesencephalic nucleus of the fifth cranial nerve, situated between the central grey and mesencephalic reticular formation, were studied in mouse embryos aged between day 9 and 15 and in postnatal day 1 mice. Nonspecific neural antibody staining allowed visualisation of the developing cranial nerves, in particular the descending mesencephalic tract. This facilitated successful dissection of the descending mesencephalic tract and trigeminal ganglion in the heads of fresh mouse embryos and postnatal mice. The fluorescent dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil), was injected into the descending mesencephalic tract in mouse embryos aged 12.5, 13.5 and 15 days of gestation and also into postnatal day 1 mice. Following a period of incubation, 100 microm sections were viewed under visible light and episcopic fluorescence. Mesencephalic neurones were observed to pass superiorly over the trigeminal ganglion and enter the maxillary division to innervate vibrissal follicle-sinus complexes, whilst none was observed innervating mandibular and maxillary intraoral structures. There was no fluorescent labelling in non-Dil injected control specimens. Using a highly specific neuronal tracer, this study shows that mesencephalic neurones in the periphery project exclusively to follicle sinus complexes in the developing mouse embryo and remain at least until postnatal day 1. These observations, contrary to those made in other animals, indicate a species specificity of mesencephalic peripheral projections.

The early development of sino-nasal mucosa.

The development of human nasal mucosa was studied in 20 fetal heads between 8 and 24 weeks of gestation. Initially the nasal cavity is lined by a single layer of flattened cells, which produces two to three layers of undifferentiated spherical cells. Olfactory epithelium lines the cranial portion of the human fetal nasal cavity at 8 weeks of gestation. Pseudostratified ciliated cuboidal or columnar epithelium appears at 9 weeks of gestation in the nasal cavity and between 14 and 16 weeks of gestation in the primitive ethmoid sinuses and maxillary sinus infundibulum. Goblet cells and glandular acini appear between 12 and 14 weeks of gestation. Initially these goblet cells/glands are found predominantly in the anterior nasal cavity but are more evenly distributed at 24 weeks of gestation. The epithelial development of the nasal septum generally precedes that of the lateral nasal wall. This study documents nasal mucosal maturation and associated anatomic development in the human fetus.

Maxillary sinus development in patients with cleft palates as compared to those with normal palates.

Maxillary sinusitis appears to be more prevalent in the cleft palate population than in the normal population. The increase in sinusitis may be due to the fact that the maxillary sinus develops differently embryonically in cleft palate patients than in those patients with normal palates. A double blind study was done by measuring the maxillary sinus cephalometric x-rays in cleft palate patients and then comparing them to patients with normally developed palates. The groups studied were 3 months to 20 years of age. It was concluded that in each of these groups there was no significant difference in size, shape, or rate of development of the maxillary sinus in cleft palate patients compared to the normal population. It is probable that the increased incidence of maxillary sinusitis in cleft palate patients is due mainly to the open palate with constant contamination of the nasal mucosa by food pushed into the nares and sinus ostia, resulting in maxillary sinusitis.

Sinonasal anatomy.

Recent advances in paranasal sinus imaging have been driven by the development of functional endoscopic sinus surgery. The goal of most sinus imaging is to provide a surgical road map delineating the anatomy, defining the obstructing lesions, and noting anatomic variations that may predispose to operative complications. We review the embryology and development of the nose and paranasal sinuses; review the radiographic anatomy of the adult sinuses and their drainage pathways; and point out variations in the normal anatomic pattern, concentrating on those variations that are significant for the functional endoscopic sinus surgeon.

Atmospheric pressure as a force that fills developing bones with marrow and air.

Many theories try to explain the existence and function of paranasal sinuses. This paper is an attempt to correlate process of paranasal sinus development in human with bone pneumatization processes in animals. It is here proposed that this mechanism starts in utero and continues after birth. During endochondral development, a solid hyaline cartilage model transforms into long bones. Central chondrocytes hypertrophy and their lacunae become confluent. Dissolving of the cartilage intercellular matrix forms a primitive marrow cavity. It is soon invaded by the periostal bud. Once circulation is established in the developing bone, the dissolved hyaline matrix can be slowly washed away from the bone cavity. Circulation in the bone cavity can develop slight subatmospheric pressures, similar to negative interstitial pressures in subcutaneous tissues. The amniotic fluid conducts atmospheric pressure to the fetal body. The pressure is trying to fill enlarging bone cavities through the existing vascular openings, or to create new openings. Bone walls of developing paranasal bones are to weak to resist the pressure gradient on their walls. New openings form on the weakest spots allowing airway mucosa to form initial paranasal sinuses. The enlarging cavities of long bones that are remote from the body surface and airway also develop a slightly subatmospheric pressure that fills them with cellular elements. These elements enter bone through the feeding vessels and form bone marrow. During after birth skeletal growth, bone remodeling shapes paranasal sinuses in a process of slow evolution that do not require measurable pressure gradients. When two sinuses come in vicinity, their growth rate declines, since the remaining thin and fragile bone lamella between them does not retract anymore.

[Unilateral choanal atresia and paranasal sinus growth]. / Atrésie choanale unilatérale et croissance sinusienne.

Mechanisms regulating sinus growth are poorly understood. We report a series of six cases of unilateral choanal atresia and discuss the role of nasal ventilation on sinus growth. The presence and the size of the sinus cavities are the main parameters. Our preliminary results suggest that sinus growth is independent of nasal ventilation.

Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis.

OBJECTIVES/HYPOTHESIS: Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF. STUDY DESIGN: Animal/basic science research. METHODS: Sinus development was studied in a porcine CF model. RESULTS: Porcine sinus epithelia expressed CFTR and exhibited transepithelial anion transport. Disruption of the CFTR gene eliminated both. Sinuses of newborn CF pigs were not infected and showed no evidence of inflammation, yet were hypoplastic at birth. Older CF pigs spontaneously developed sinus disease similar to that seen in humans with CF. CONCLUSIONS: These results define a role for CFTR in sinus development and suggest the potential of the CF pig as a genetic model of CF-sinus disease in which to test therapeutic strategies to minimize sinus-related CF morbidity.

The drainage system of the paranasal sinuses: a review with possible implications for balloon catheter dilation.

BACKGROUND: Intersinus connections and accessory ostia of the maxillary sinus are well known to rhinologic surgeons but are less known for the remaining paranasal sinuses. Probing and dilatation of the natural ostia of diseased sinuses is being popularized currently by the clinical value of balloon catheter dilation (BCD). Although short-term high success rates with treatment of the dilated ostia/duct have been reported with this technique, the potential impact of fractures of adjacent bony septae on accessory sinus ostia, on mucosally lined surfaces, and on intersinus drainage pathways still has not been considered. The aim of this study was to review the literature on accessory sinus ostia, intersinus connections, and mucociliary drainage pathways for the entire sinus system that are relevant to BCD. METHODS: A literature review was performed. RESULTS: Accessory sinus ostia exist for each paranasal sinus. Many sinuses drain not only directly into the nasal cavity but also indirectly through adjacent sinuses. Of note, one major drainage pathway of the frontal sinus is over the ethmoid sinuses and via the ethmoids into the maxillary sinus and subsequently into the nose. Drainage of the sphenoid sinus exists both through posterior ethmoidal cells and directly into the nasopharynx. CONCLUSION: Accessory ostia are not only common for the maxillary sinus but also for the entire paranasal sinus system. BCD may potentially inadvertently impair mucociliary clearance of the sinuses through effects on secondary drainage pathways.

Revisiting human nose anatomy: phylogenic and ontogenic perspectives.

This review suggests revisiting nose anatomy by considering the ethmoidal labyrinths as part of the olfactory nose and not as paranasal sinuses. Phylogenetically, the olfactory and respiratory organs of the most primitive vertebrates are separated. Exaptation, a mechanism of evolution, may explain the fusion of the olfactory and respiratory organs in dipnoi. The respiratory and olfactory noses remain anatomically separated by the transverse lamina in most mammals, whose olfactory labyrinth is a blind recess housing the ethmoturbinates. In humans, the partitioning between the olfactory cleft and the ethmoid labyrinth seems to be a consequence of ethmoid bone remodeling induced by the acquisition of an upright posture. The ethmoid bone is derived from the cartilaginous nasal capsule of primitive vertebrates and considered to be a highly conserved region among the bony elements of the skull base. It appears to be involved only in housing and protecting the olfactory function. During the early stages of human fetal development, rupture of the oronasal membrane leads to the integration of the primary olfactory sac in the future respiratory organ. The cartilaginous nasal capsule appears in the tissue under the brain and around the olfactory channels. Its early fetal development is classically regarded as the beginning of paranasal sinus formation. From phylogenic and ontogenic perspectives, it may be regarded as the development of the olfactory labyrinth as modified by the remodeling process of the human face and skull base. The endochondral bony origin of the ethmoid labyrinths makes them substantially different from the other paranasal sinuses.

The maxillary sinus in three genera of new world monkeys: factors that constrain secondary pneumatization.

The air filled cavities of paranasal sinuses are thought by some to appear opportunistically in spatial "gaps" within the craniofacial complex. Anthropoid primates provide excellent natural experiments for testing this model, since not all species possess a full complement of paranasal sinuses. In this study, two genera of monkeys (Saguinus and Cebuella) which form maxillary sinuses (MS) as adults were compared to squirrel monkeys (Saimiri spp.), in which a MS does not form. Using microCT and histomorphometric methods, the spatial position of paranasal spaces was assessed and size of the adjacent dental sacs was measured. In Saguinus, secondary pneumatization is underway perinatally, and the sinus extends alongside deciduous premolars (dp). The MS overlaps all permanent molars in the adult. In Saimiri, the homologous space (maxillary recess) extends no farther posterior than the first deciduous premolar at birth and extends no farther than the last premolar in the adult. Differences in dental size and position may account for this finding. For example, Saimiri has significantly larger relative dp volumes, and enlarged orbits, which encroach on the internasal space to a greater degree when compared to Saguinus. These factors limit space for posterior expansion of the maxillary recess. These findings support the hypothesis that secondary pneumatization is a novel, opportunistic growth mechanism that removes "unneeded" bone. Moreover, paranasal spaces occur in association with semiautonomous skeletal elements that border more than one functional matrix, and the spatial dynamics of these units can act as a constraint on pneumatic expansion of paranasal spaces.

Fate of the nasal capsular cartilages in prenatal and perinatal tamarins (Saguinus geoffroyi) and extent of secondary pneumatization of maxillary and frontal sinuses.

Development of the nasal capsule cartilages was studied in seven Geoffroy's tamarins (Saguinus geoffroyi), including one fetus, five neonates and one infant. Four additional postnatal specimens of the genus were studied (one 5-month-old and three adults) to determine the magnitude of postnatal expansion of the paranasal sinuses. Alcian blue histochemistry and osteopontin immunohistochemistry were employed in selected subadult specimens to characterize cartilage matrix. The fetal S. geoffroyi possesses a continuous nasal capsule, including a zona anularis; the primordial maxillary sinuses are surrounded by cartilage. Secondary pneumatization is in progress in all older specimens, which have sinuses that are more than twofold larger compared to that of the fetus. Results indicate that extensive ossification of the middle part of the nasal capsule (pars intermedia) is occurring in the perinatal timeframe, forming portions of the ethmoid bone. Anteriorly, the nasal capsule comprises isolated fragments in perinatal specimens, which are fewer and smaller in the infant and in a 5-month-old S. midas, and nearby multinucleate cells suggest that osteoclasts break apart these initially continuous elements. Fragments of the pars intermedia and the tectum nasi are found transiently between mucosa and the sites of secondary pneumatization. The maxillary sinus mucosa is highly vascular in most perinatal specimens. Histochemical and immunohistochemical findings show that cartilage of endochondral bones and non-ossifying parts are distinct in the perinatal time period. These results indicate that breakdown of the capsular cartilage precedes secondary pneumatization as previously suggested. There are portions of the cartilage of the recessus maxillaris and tectum nasi that transiently block mucosa from interfacing directly with bone. Vascularization may play a role in the breakdown of cartilages as well as the onset of secondary pneumatization. Since cartilage has the capacity to produce substances that trigger angiogenesis and bone resorption, further detailed characterization of the cartilage bordering sites of secondary pneumatization is merited.