Embryonic requirements for Tcf12 in the development of the mouse coronal suture.

A major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in either of the bHLH transcription factors TWIST1 and TCF12. Although compound heterozygous Tcf12; Twist1 mice display severe coronal synostosis, the individual role of Tcf12 had remained unexplored. Here, we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement for Tcf12 in suture formation, as combined deletion of Tcf12 in embryonic neural crest and mesoderm, but not in postnatal suture mesenchyme, disrupts the coronal suture. We also detected asymmetric distribution of mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. In Tcf12 mutants, reduced asymmetry is associated with bones meeting end-on-end, possibly contributing to synostosis. Our results support embryonic requirements of Tcf12 in proper formation of the overlapping coronal suture.

Onabotulinumtoxina (craniotomy scar combined with cranial suture line injections) for persistent post craniotomy headache: Case series with long-term follow-up.

BACKGROUND: There is no defined preventive treatment protocol for persistent post-craniotomy headache. In several small case series and individual case reports onabotulinumtoxinA injected into the craniotomy scar has shown possible efficacy. What is lacking is long term follow-up and if focusing on the cranial suture lines along with the craniotomy scar can enhance improvement and provide more sustained benefit. METHODS: Retrospective chart review with case series. RESULTS: Four patients (three women, one man) with ICHD-3 defined persistent post craniotomy headache were treated using a novel onabotulinumtoxinA injection protocol. All the patients presented with continuous head pain of moderate to severe intensity. All had severe allodynia on the side of their craniotomy. All had significant reduction in quality of life. Our application of onabotulinumtoxinA involved injection into both the surgical scar and the transected/irritated cranial suture lines noted on neuroimaging and physical examination. With treatment all patients demonstrated significant benefit including a reduction in daily pain intensity (75%-100%), developing periods of pain freedom (2-7 days per week) and having a dramatic improvement in quality of life (close to 100% in all). The benefit was sustained for at least five years of follow-up. CONCLUSION: From our case series it appears that injection not only along the painful craniotomy scar but into the involved cranial suture lines provides positive efficacy and sustained improvement in patients with persistent post craniotomy headache.

Age estimation from median palatine suture using computed tomography reconstructed 3D images: a comparison of Northern and Southwestern Chinese populations.

To investigate the potential of computed tomography (CT) images of median palatine suture (MP) for adult age estimation in the Northern and Southwestern Chinese populations. A total of 1110 cranial CT scans from individuals aged 10-79 years, including 557 northern Chinese and 553 southwestern Chinese, were collected for analysis. After volume reformation and multiplanar reconstruction, a total of 20 slices of median palatine suture were selected from each individual. The closure of sutures was analyzed into four stages, and the cumulative scores of 20 slices were recorded as the suture closure score (SCS). The correlations between SCS and age were compared among the two Chinese populations residing in diverse geographic regions. Regression models were established for age estimation. The estimation accuracy was evaluated based on the test set. The mean absolute error (MAE) and the correlation between predicted age and chronological age were calculated to evaluate estimation accuracy. The SCS of MP exhibited a significant correlation with age (0.613, northern male; 0.678, southwestern male; 0.730, northern female; 0.704, Southwestern female; 0.662, total). Furthermore, there were statistically significant differences in SCS among different regions and sex groups (p < 0.001). The cubic regression model had the highest R2 value in all subjects, especially among Northern females and Southwestern males, while the power and quadratic regression models showed the highest R2 value in Northern males and Southwestern females, respectively. In the test set, the Northern cohort demonstrated a lower MAE (9.06 ± 7.32 years, males; 9.17 ± 5.28 years, females) compared to the Southwestern cohort (9.19 ± 7.49 years, male; 10.61 ± 6.83 years, female). Additionally, it was observed that males exhibited a lower MAE than females in both regional groups. This study demonstrated the potential utility of CT images of the MP for age estimation in Chinese populations, emphasizing the significance of incorporating regional and sex factors within this context.

Spatial transcriptomics reveals a role for sensory nerves in preserving cranial suture patency through modulation of BMP/TGF-ß signaling.

The patterning and ossification of the mammalian skeleton requires the coordinated actions of both intrinsic bone morphogens and extrinsic neurovascular signals, which function in a temporal and spatial fashion to control mesenchymal progenitor cell (MPC) fate. Here, we show the genetic inhibition of tropomyosin receptor kinase A (TrkA) sensory nerve innervation of the developing cranium results in premature calvarial suture closure, associated with a decrease in suture MPC proliferation and increased mineralization. In vitro, axons from peripheral afferent neurons derived from dorsal root ganglions (DRGs) of wild-type mice induce MPC proliferation in a spatially restricted manner via a soluble factor when cocultured in microfluidic chambers. Comparative spatial transcriptomic analysis of the cranial sutures in vivo confirmed a positive association between sensory axons and proliferative MPCs. SpatialTime analysis across the developing suture revealed regional-specific alterations in bone morphogenetic protein (BMP) and TGF-ß signaling pathway transcripts in response to TrkA inhibition. RNA sequencing of DRG cell bodies, following direct, axonal coculture with MPCs, confirmed the alterations in BMP/TGF-ß signaling pathway transcripts. Among these, the BMP inhibitor follistatin-like 1 (FSTL1) replicated key features of the neural-to-bone influence, including mitogenic and anti-osteogenic effects via the inhibition of BMP/TGF-ß signaling. Taken together, our results demonstrate that sensory nerve-derived signals, including FSTL1, function to coordinate cranial bone patterning by regulating MPC proliferation and differentiation in the suture mesenchyme.

Craniosynostosis: orofacial and oral health perspectives with masticatory insights.

BACKGROUND: Craniosynostosis (CS), premature fusion of one or more cranial sutures, leads to abnormal skull development, impacting both facial esthetics and oral function. This study aimed to evaluate the specific orofacial and oral health characteristics, including masticatory performance, in Thai patients with CS. METHODS: A comparative study was conducted with Thai CS patients aged 6-17 years and a control group of healthy individuals with similar age distribution. Assessments included craniofacial morphology, oral health status, and masticatory performance. Intergroup comparisons utilized appropriate statistical tests. RESULTS: The study included 24 CS patients with a mean age of 10.11 ± 2.98 years and 30 controls. CS patients exhibited a significantly higher prevalence of various oral conditions compared to controls: cleft palate (20.8%), anterior open bite (41.7%), anterior crossbite (54.2%), posterior crossbite (50%), combined anterior-posterior crossbite (45.8%), dental crowding in both maxilla and mandible (50% and 45.8% respectively), congenitally missing teeth (50%), supernumerary teeth (12.5%), and eruption failure (54.2%). Furthermore, CS patients exhibited significantly higher caries prevalence and susceptibility, alongside poorer oral hygiene, compared to controls. Regarding jaw relationships, CS patients exhibited a significantly higher proportion of Angle's Class III malocclusion (50%) compared to the control group, where Class I malocclusion was predominant (50%). Masticatory performance, assessed using the two-color gum mixing ability test, showed significantly higher hue variance in CS patients (0.12 ± 0.07) compared to the control group, indicating reduced chewing performance. CONCLUSION: This study underscores the significant orofacial and oral health challenges faced by children with CS, including a high prevalence of malocclusions, dental anomalies, elevated caries experience, and compromised masticatory function. These findings emphasize the importance of tailored interventions and comprehensive oral healthcare strategies to address the unique needs of this population and improve their overall quality of life.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

Technical evolution of pediatric neurosurgery: craniosynostosis from 1972 to 2023 and beyond.

Very few clinical entities have undergone so many different treatment approaches over such a short period of time as craniosynostosis. Surgical treatments for this condition have ranged from simple linear craniectomies, accounting for the specific role of cranial sutures in assuring the normal growth of the skull, to more complex cranial vault reconstructions, based on the perceived role of the skull base in affecting the growth of the skull. While a great deal of evolution has occurred, there remains controversy regarding the ideal treatment including the best surgical technique, the optimal age for surgery, and the long-term morphological and neurodevelopmental outcomes. The evolution of the surgical management of craniosynostosis in the last 50 years has been affected by several factors. This includes the awareness of needing to operate on affected children during infancy to achieve the best results, the use of multistage operations, the availability of more sophisticated surgical tools, and improved perioperative care. In some forms of craniosynostosis, the operations can be carried out at a very young age with low morbidity, and with the postoperative use of a molding helmet, springs, or distractors, these operations prove to be as effective as traditional larger cranial reconstructions performed in older children. As a consequence, complex surgical operations have become progressively less utilized. A second relevant advance was the more recent advent of a molecular diagnosis, which allowed us to understand the pathogenesis of some associated malformations and neurodevelopmental issues that were observed in some children despite appropriate surgical treatment. Future research should focus on improving the analysis of longer-term outcomes and understanding the natural history of craniofacial conditions, including what issues persist despite optimal surgical correction. Progress in molecular investigations concerning the normal and pathological development of cranial sutures could be a further significant step in the management of craniosynostosis, possibly favoring a "medical" treatment in the near future. Artificial intelligence will likely have a role in establishing the diagnosis with less reliance on radiographic studies and in assisting with surgical planning. Overall, much progress has been made, but there remains much to do.

UCSQ Method Applied on 3D Photogrammetry: Non-Invasive Objective Differentiation Between Synostotic and Positional Plagiocephaly.

OBJECTIVE: Objective differentiation between unilateral coronal synostosis (UCS) and positional posterior plagiocephaly (PPP) based on 3D photogrammetry according to Utrecht Cranial Shape Quantificator (UCSQ). DESIGN: Retrospective study. SETTING: Primary craniofacial center. PATIENTS, PARTICIPANTS: Thirty-two unoperated patients (17 UCS; 15 PPP) (age < 1 year). INTERVENTIONS: Extraction of variables from sinusoid curves derived using UCSQ: asymmetry ratio forehead and occiput peak, ratio of gradient forehead and occiput peak, location forehead and occiput peak. MAIN OUTCOME MEASURE(S): Variables, derived using 3D photogrammetry, were analyzed for differentiation between UCS and PPP. RESULTS: Frontal peak was shifted to the right side of the head in left-sided UCS (mean x-value 207 [192-220]), and right-sided PPP (mean x-value 210 [200-216]), and to the left in right-sided UCS (mean x-value 161 [156-166]), and left-sided PPP (mean x-value 150 [144-154]). Occipital peak was significantly shifted to the right side of the head in left-sided PPP (mean x-value 338 [336-340]) and to the left in right-sided PPP (mean x-value 23 [14-32]). Mean x-value of occipital peak was 9 (354-30) in left- and 2 (350-12) in right-sided UCS. Calculated ratio of gradient of the frontal peak is, in combination with the calculated asymmetry ratio of the frontal peak, a distinctive finding. CONCLUSIONS: UCSQ objectively captures shape of synostotic and positional plagiocephaly using 3D photogrammetry, we therefore developed a suitable method to objectively differentiate UCS from PPP using radiation-free methods.

A study of 285 cases of cranial vault suture closure in Chinese adults.

PURPOSE: To examine the presence and characteristics of cranial vault suture closure in Chinese adults and to explore whether craniosacral therapy (CST) manipulation is rational from the anatomical perspective. METHODS: Anthropological non-metric observation and craniometry were used to study 285 dry skull specimens of Chinese adults. RESULTS: A total of 91 specimens with closed extracranial sutures were observed, with an occurrence rate of 31.93%. Based on the mode of closure, there were 32 cases of single type closure, with sagittal suture closure predominating with 20 cases (21.98%); 59 cases of composite closure, with a partial closure of coronal suture + sagittal suture + lambdoid suture predominating with 26 cases (28.57%). In terms of the degree of closure, there were 13 cases (14.28%) of sagittal suture grade 0 closure and 78 cases (85.72%) of grade 1 - 4 closure; 34 cases (37.36%) of coronal suture grade 0 closure and 57 cases (62.64%) of grade 1 - 4 closure; 47 cases (51.65%) of lambdoid suture grade 0 closure and 44 cases (48.35%) of grade 1 - 4 closure. The segment and degree of coronal suture closure (46, 80.7%) and lambdoid suture (31, 70.45%) were mostly left-right symmetrical. The bone surfaces on either side of the cranial vault sutures are embedded in each other, forming a rough, complex and interlocking bone-suture-bone structure. CONCLUSION: This study observed the closure of the cranial vault suture, summarized its characteristics, and explored the irrationality of the CST manipulation. The anatomical characteristics of the cranial suture dictate that manipulation cannot push the cranial suture at will.

Developmental changes in the occipital cranial sutures of children less than 2 years of age.

PURPOSE: The occipital bone is located on the boundary between the membranous and cartilage bones and contains a wide variety of accessory sutures. In this study, we describe the age distribution of pediatric patients who are less than 2 years of age with occipital cranial sutures using a three-dimensional computed tomography (3D-CT). METHODS: A total of 167 consecutive patients who are less than 2 years of age and underwent computed tomography for head trauma were included in this study. RESULTS: Based on the results of this study, various types of sutures were observed among the pediatric participants. In particular, superior median fissures, mendosal sutures, other interparietal segment's accessory sutures, and interparietal sutures were noted in 21%, 35%, 9%, and 6% of the participants, respectively. Additionally, Wormian bones within the lambdoid suture were noted in 32% of the patients. The median age of children with superior median fissure and mendosal suture was 0 month. Meanwhile, superior median fissure was not observed among children older than 5 months of age. In this population, 13 patients (8%) were found to have skull fracture. CONCLUSIONS: Knowledge of the normal cranial anatomy and developmental patterns of cranial sutures is crucial in the evaluation of questionable fractures in the occipital region. A combination of 3D-CT and axial bone window imaging is useful in differentiating normal structures from pathological changes in the cranium.