Metopic synostosis: Defining the temporal sequence of normal suture fusion and differentiating it from synostosis on the basis of computed tomography images

Only the metopic suture normally fuses during early childhood; all other cranial sutures normally fuse much later in life. Despite this, metopic synostosis is one of the least common forms of craniosynostosis. The temporal sequence of normal physiologic metopic suture fusion remains undefined and controversial. Therefore, diagnosis of metopic synostosis on the basis of computed tomography images alone can prove misleading. The present study sought to determine the normal sequence of metopic suture fusion and characterize both endocranial and ectocranial suture morphology. An analysis of computed tomography scans of 76 trauma patients, ranging in age from 10 days to 18 months, provided normative craniofacial data that could be compared to similar data obtained from the preoperative computed tomography scans of 30 patients who had undergone surgical treatment for metopic synostosis. Metopic suture fusion was complete by 6 to 8 months in all nonsynostotic patients, with initiation of suture fusion evident as early as 3 months of age. Fusion was found to commence at the nasion, proceed superiorly in progressive fashion, and conclude at the anterior fontanelle. Although an endocranial ridge was not commonly seen in synostotic patients, an endocranial metopic notch was virtually diagnostic of premature suture fusion and was seen in 93 percent of synostotic patients. A metopic notch was not seen in any nonsynostotic patient. The morphologic and normative craniofacial data presented permit diagnosis of metopic synostosis based on computed tomography images obtained beyond the normal fusion period.     

Facial suture synostosis of newborn Fgfr1(P250R/+) and Fgfr2(S252W/+) mouse models of Pfeiffer and Apert syndromes

Apert and Pfeiffer syndromes are hereditary forms of craniosynostosis characterized by midfacial hypoplasia and malformations of the limbs and skull. A serious consequence of midfacial hypoplasia in these syndromes is respiratory compromise due to airway obstruction. In this study, we have evaluated Fgfr1(P250R/+) and Fgfr2(S252W/+) mouse models of these human conditions to study the pathogenesis of midfacial hypoplasia. Our histologic and micro-CT evaluation revealed premature synostosis of the premaxillary-maxillary, nasal-frontal, and maxillary-palatine sutures of the face and dysplasia of the premaxilla, maxilla, and palatine bones. These midfacial abnormalities were detected in the absence of premature ossification of the cranial base at postnatal day 0. Our results indicate that midfacial hypoplasia is not secondary to premature cranial base ossification but rather primary synostosis of facial sutures. Birth Defects Research (Part A), 2011.     

Blood gases in craniocerebral hypothermia

Experiments were conducted on dogs; cranio-cerebral hypothermia (a reduction of body temperature from 38 to 28 degrees C) led to increase of oxygen and to reduction of carbon dioxide tension in the blood. In case of marked hypothermia (24 degrees C) the blood gaseous concentration became less than at 28 degrees C, but remained above the initial level. This indicates prolonged preservation of adequate lung ventilation in the hypothermic organism.     

The sutural pattern of skull-roof bones in Lower Permian Discosauriscus austriacus from Moravia

Sutures between ornamented bones of Discosauriscus austriacus are mostly simple, but there are also more complicated, rarely serrated, sutures between some bones. In small individuals, the sutures are simple, but the same sutures also occur in the largest specimens. The character of the sutures and the incomplete ossification of bones around the pineal foramen indicate the larva type of organization of Discosauriscus The fenestra between premaxillaries and nasals appears to be absent. In the majority of specimens, a squamosal-intertemporal sutural contact is present, althought it is sometimes reduced and in a few cases interrupted by a postorbital and supratemporal contact Therefore the character 'intertemporal-squamosal suture present or absent' cannot be used in this rigorous sense for testing the relationships of early tetrapods. The configuration of the suture between both parietals in osteolepiforms, Discosauriscus , and various early amphibians and reptiles indicates that the bones enclosing the pineal foramen in osteolepifonns are frontals. *** D iscosauriscus . Seymouriamorpha, Lower Permian tetrapod, skull exoskeleton, sutures.     

A Phylogenetic Study of Late Growth Events in a Mammalian Evolutionary Radiation—The Cranial Sutures of Terrestrial Artiodactyl Mammals

We recorded the relative timing of fusion of 29 ectocranial sutures in 480 skulls belonging to 35 extant and four fossil species from all major clades of terrestrial artiodactyls. The resulting data were studied in a phylogenetic context, using mapping of event-pairing of suture fusion events and Parsimov. As phylogenetic framework we generated a compound phylogeny from several previously published analyses. Overall suture closure per species ranged from five to all 29 sutures in Hexaprotodon. All living non-ruminants (suids, camelids, and hippopotamids) fuse more than 50% of the studied sutures (most over 75%), whereas in almost all ruminants less than 50% of the sutures fuse completely. Phylogenetic regression found a significant correlation between suture closure and body mass. In all species we observed an early fusion of the sutures surrounding the foramen magnum (Exoccipital-Supraoccipital, Exoccipital-Basioccipital), a consistent scheme also among other mammals. Scaling the number of changes to the number of sutures in each of the usually recognized skull modules reveals relatively equal numbers of changes in the cranial vault, the zygomatic-sphenoid region, the orbit, and the anterior oral-nasal region. Only the basicranium shows a much smaller number in terms of absolute and relative amount of suture fusion change. Some species show a unique pattern of suture fusion, such as the early fusion of many sutures in the palatal region in Pecari or that of premaxillary sutures in †Cainotherium, perhaps related to feeding mode. A strategy to strengthen the skull by obliterating the sutures could explain the pattern of increased sutural fusion in ruminant species with large cranial appendages.     

Calvarial sutural abnormalities: metopic synostosis and coronal deformation--an anatomic, three-dimensional radiographic, and pathologic study

The purposes of this study were (1) to evaluate the histologic differences between synostotic versus deformational suture abnormalities and (2) to correlate these histologic findings with anatomic and three-dimensional computed tomographic (CT) scans. We examined three infants with premature metopic synostosis; one infant also had microcephaly trisomy 13 and curious overriding of the coronal sutures. The three-dimensional CT scans demonstrated obliteration of the metopic suture inferiorly. Histologic sections of this suture showed complete bony stenosis. The same pattern was found in all three infants, including the two infants with trigonocephaly who did not have trisomy 13 or microcephaly. In the trisomy 13 infant, the overlapped inferior coronal suture was obliterated on CT examination. However, histologic sections in this region showed a merging of bone; there was no synostosis. In summary, three-dimensional CT re-formation correlated with metopic suture histology. "Stenotic" fusion existed in all infants with trigonocephaly, those with normal and abnormal karyotypes, with and without microcephaly. However, three-dimensional CT re-formation of the trisomic infant showed opacification of the coronal suture in the areas of greatest overlap, whereas histology revealed a curious bone remodeling pattern, possibly a precursor to "deformational" craniosynostosis.     

Mechanical properties of cranial sutures

Many bones in mammalian skulls are linked together by cranial sutures, connective tissue joints that are morphologically variable and show different levels of interdigitation among and within species. The goal of this investigation was to determine whether sections of skull with cranial sutures have different mechanical properties than adjacent sections without sutures, and if these properties are enhanced with increased interdigitation. To test these hypotheses, bending strength and impact energy absorption were measured for samples of goat (Capra hircus) cranial bone without sutures and with sutures of different degrees of interdigitation. Bending strength was measured under both dynamic (9.7 mm displacement s-1) and relatively static (0.8 mm s-1) conditions, and at either speed, increased sutural interdigitation provided increased strength during three-point bending. However, except for very highly interdigitated sutures loaded slowly, sutures were not as strong in bending as bone. In contrast, sutures absorbed from 16% to 100% more energy per unit volume during impact loading than did bone. This five-fold increase in energy absorption by the sutures was significantly correlated with increased sutural interdigitation.     

Characteristics of the infant Apert skull and its subsequent development

The purpose of the paper is to describe and analyze the infant Apert skull with emphasis on the calvaria and its early postnatal development. Skull radiographs of 16 Apert syndrome patients were examined (12 American, 4 Danish; 8 males, 8 females). The criterion for inclusion in the study was that the first skull film had to be obtained before 1 year of age. Study methods employed included plain skull radiographs, roentgencephalometric films in several projections, CT-scans, and 3-D reconstructions. Data from 2 dry skulls and 2 early cases from the literature were also evaluated The following findings were common to all cases during early infancy (less than 3 months): The coronal suture area was prematurely closed and was represented by a bone condensation line beginning at the cranial base, extending upwards, and having a characteristic posterior convexity. Anterior and posterior fontanelles were widely patent. The midline of the calvaria had a gaping defect which extended from the glabellar area to the posterior fontanelle via the metopic suture area, anterior fontanelle, and sagittal suture area. Bony islands of varying sizes were observed in the midline defect. The calvaria was hypomineralized. During the first 2-4 years of life, the midline defect was obliterated by coalescence of the enlarging bony islands without evidence of any proper formation of sutures. The calvaria became thicker with time and several cases developed increased digital markings and enlargement of the sella turcica. During infancy, the Apert skull with its gaping midline defect appears to permit adequate accommodation of the growing brain, albeit distorted in shape. Normal metopic, sagittal, and coronal sutures with interdigitations were not observed in a single instance; in contrast, the lambdoidal sutures appeared normal in all cases. The invariable findings of an extremely short squama and orbital part of the frontal bone together with the posterior convexity of the coronal bone condensation line suggest that growth inhibition in the sphenofrontal and coronal suture area has its onset very early in fetal life.     

Nervous reactivity disturbances in patients with late post-traumatic encephalic syndromes.

A polygraphic study performed on 184 patients with late post-traumatic encephalic syndromes has shown marked nervous reactivity disturbances. The disturbances, estimated by testing for the electrographic components of the orienting reflex elicited by a repetitive auditory stimulus and for their habituation, were expressed by alterations in the intensity, resistance to habituation and sequence of habituation of the somatic, autonomic and EEG components. The character and severity of these disturbances depended on the mechanism behind the syndrome-inducing cranio-cerebral trauma, site of the impact and clinical picture of the syndrome.     

Humeroradial synostosis

Summary A 1-year-old female child with congenital humeroradial synostosis, who also had microphthalmia and coloboma of the iris and choroidea is described. This is the second case in the literature in which chromosomal studies have revealed no abnormalities. Dermatoglyphic studies are also described.     

A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plastiCity among diplomonads and significant lateral gene transfer in eukaryote genome evolution

Background

Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. To better understand the molecular control of human suture morphogenesis we used microarray analysis to identify genes differentially expressed during suture fusion in children with craniosynostosis. Expression differences were also analysed between each unfused suture type, between sutures from syndromic and non-syndromic craniosynostosis patients, and between unfused sutures from individuals with and without craniosynostosis.

Results

We identified genes with increased expression in unfused sutures compared to fusing/fused sutures that may be pivotal to the maintenance of suture patency or in controlling early osteoblast differentiation (i.e. RBP4, GPC3, C1QTNF3, IL11RA, PTN, POSTN). In addition, we have identified genes with increased expression in fusing/fused suture tissue that we suggest could have a role in premature suture fusion (i.e. WIF1, ANXA3, CYFIP2). Proteins of two of these genes, glypican 3 and retinol binding protein 4, were investigated by immunohistochemistry and localised to the suture mesenchyme and osteogenic fronts of developing human calvaria, respectively, suggesting novel roles for these proteins in the maintenance of suture patency or in controlling early osteoblast differentiation. We show that there is limited difference in whole genome expression between sutures isolated from patients with syndromic and non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR. Furthermore, distinct expression profiles for each unfused suture type were noted, with the metopic suture being most disparate. Finally, although calvarial bones are generally thought to grow without a cartilage precursor, we show histologically and by identification of cartilage-specific gene expression that cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal sutures.

Conclusion

This study has provided further insight into the complex signalling network which controls human calvarial suture morphogenesis and craniosynostosis. Identified genes are candidates for targeted therapeutic development and to screen for craniosynostosis-causing mutations.     

Nasal capsular cartilage is required for rat transpalatal suture morphogenesis

In the cranial vault, suture morphogenesis occurs when the growing cranial bones approximate and overlap or abut one another. Patency of developing sutures is regulated by the underlying dura mater. Once cranial sutures form, bone growth proceeds from the sutures in response to growth signals from the rapidly expanding neurocranium. Facial sutures do not develop in contact with the dura mater. It was therefore hypothesized that facial suture morphogenesis and bone growth from facial sutures are regulated by tissues with an equivalent role to the dura mater. The present study was designed to test this hypothesis by characterizing the morphology and growth factor expression in developing transpalatal (TP) sutures and their surrounding tissues, and then assessing the role of the overlying nasal capsular (NC) cartilages in maintaining suture patency. TP sutures develop as overlapping sutures, similar to cranial coronal sutures, and expression of Tgf-betas in TP sutures was similar to their distribution in cranial coronal sutures. To establish whether NC cartilages play a role in regulating TP suture morphogenesis, fetal rat TP sutures were cultured with associated attached NC cartilages or with NC cartilages removed. Sutures cultured for upward of 5 days with intact NC cartilages remained patent and maintained their cellular and fibrous components. However, in the absence of NC cartilages, the cellular nature of the sutures was not maintained and they became progressively acellular, with bony bridging across the suture. This finding is similar to that for cranial vault sutures cultured in the absence of dura mater, indicating that NC cartilages play an equivalent role to dura mater in maintaining the patency of developing sutures. These studies indicate that tissue interactions likely regulate morphogenesis of all cranial and facial sutures.     

Fusion Patterns in the Skulls of Modern Archosaurs Reveal That Sutures Are Ambiguous Maturity Indicators for the Dinosauria

The sutures of the skulls of vertebrates are generally open early in life and slowly close as maturity is attained. The assumption that all vertebrates follow this pattern of progressive sutural closure has been used to assess maturity in the fossil remains of non-avian dinosaurs. Here, we test this assumption in two members of the Extant Phylogenetic Bracket of the Dinosauria, the emu, Dromaius novaehollandiae and the American alligator, Alligator mississippiensis, by investigating the sequence and timing of sutural fusion in their skulls. As expected, almost all the sutures in the emu skull progressively close (i.e., they get narrower) and then obliterate during ontogeny. However, in the American alligator, only two sutures out of 36 obliterate completely and they do so during embryonic development. Surprisingly, as maturity progresses, many sutures of alligators become wider in large individuals compared to younger, smaller individuals. Histological and histomorphometric analyses on two sutures and one synchondrosis in an ontogenetic series of American alligator confirmed our morphological observations. This pattern of sutural widening might reflect feeding biomechanics and dietary changes through ontogeny. Our findings show that progressive sutural closure is not always observed in extant archosaurs, and therefore suggest that cranial sutural fusion is an ambiguous proxy for assessing maturity in non-avian dinosaurs.     

Experimental and clinical applications of fibrin glue

A 2-year experience with laboratory and clinical applications of fibrin glue is presented. An autologous technique, which eliminates the danger of multidonor preparations, has been developed in our blood bank. While one can obtain different fibrinogen concentrations from the same amount of a patient's blood, in vitro mechanical testing demonstrated that at higher fibrinogen concentrations there is an increase in shear adhesive strength. Evaluation of skin-graft take in 16 Sprague-Dawley rats did not demonstrate significant differences in healing when adhesive use was compared with suture technique. In a clinical study, four different groups of patients (facial burns, hand burns, difficult graft sites, and miscellaneous surgical applications) benefited from autologous or single-donor fibrin glue for a total of 82 cases. There are several distinct advantages to the use of fibrin adhesive: The autologous technique eliminates the risk of transmissible viral diseases (AIDS, hepatitis); it can be used as a sealant in the treatment of seromas, dural leaks, and lymphoceles; and it improves hemostasis and early graft adherence. Face and hands are resurfaced with sheet grafts in a single procedure, obtaining a better aesthetic result with complete graft take and immediate start of physical therapy. Neither sutures nor pressure dressings are required. The minimal postoperative care associated with early return to normal activities seems to increase the satisfaction of patients and nurse personnel.