Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

Most cases of Apert syndrome are caused by mutations in the FGFR2 gene, either Ser252Trp or Pro253Arg. In these patients, over the last decades, spring-assisted posterior vault expansion (SA-PVE) has been the technique of choice for cranial vault expansion in the Craniofacial Unit of Great Ormond Street Hospital for Children (GOSH), London. The aim of this study was to investigate if there is a difference in preoperative intracranial volume (ICV) in patients with Apert syndrome with Ser252Trp or Pro253Arg mutation and whether these mutations affect the change in ICV achieved by SA-PVE. The GOSH craniofacial SA-PVE database was used to select patients with complete genetic testing and preoperative and postoperative computed tomography scans. ICV was calculated using FSL (FMRIB Analysis Group, Oxford) and adjusted based on Apert-specific growth curves. Sixteen patients were included with 8 having Ser252Trp mutation and 8 having Pro253Arg mutation. The mean preoperative adjusted computed tomography volume for patients in the Ser252Trp group was 1137.7 cm3 and in the Pro253Arg group was 1115.8 cm3 (P=1.00). There was a significant increase in ICV following SA-PVE in all patients (P<0.001) with no difference in mean change in ICV between the groups (P=0.51). Four (50%) patients with Ser252Trp mutation and 3 (37.5%) with Pro253Arg mutations required a second operation after primary SA-PVE. The results demonstrate that regardless of the mutation present, SA-PVE was successful in increasing ICV in patients with Apert syndrome and that a repeat volume expanding procedure was required by a similar number of patients in the 2 groups

A new efficient trial design for assessing reliability of ankle-brachial index measures by three different observer groups

BACKGROUND: The usual method of assessing the variability of a measure such as the ankle brachial index (ABI) as a function of different observer groups is to obtain repeated measurements. Because the number of possible observer-subject combinations is impractically large, only a few small studies on inter- and intraobserver variability of ABI measures have been carried out to date. The present study proposes a new and efficient study design. This paper describes the study methodology. METHODS: Using a partially balanced incomplete block design, six angiologists, six primary-care physicians and six trained medical office assistants performed two ABI measurements each on six individuals from a group of 36 unselected subjects aged 65–70 years. Each test subject is measured by one observer from each of the three observer groups, and each observer measures exactly six of the 36 subjects in the group. Each possible combination of two observers occurs exactly once per patient and is not repeated on a second subject. The study involved four groups of 36 subjects (144), plus standbys. RESULTS: The 192 volunteers present at the study day were similar in terms of demographic characteristics and vascular risk factors: mean age 68.6 ± 1.7; mean BMI 29.1 ± 4.6; mean waist-hip ratio 0.92 ± 0.09; active smokers 12%; hypertension 60.9%; hypercholesterolemia 53.4%; diabetic 17.2%. A complete set of ABI measurements (three observers performing two Doppler measurements each) was obtained from 108 subjects. From all other subjects at least one ABI measurement was obtained. The mean ABI was 1.08 (± 0.13), 15 (7.9%) volunteers had an ABI <0.9, and none had an ABI >1.4, i.e. a ratio that may be associated with increased stiffening of the arterial walls. CONCLUSION: This is the first large-scale study investigating the components of variability and thus reliability in ABI measurements. The advantage of the new study design introduced here is that only one sixth of the number of theoretically possible measurements is required to obtain information about measurement errors. Bland-Altman plots show that there are only small differences and no systematic bias between the observers from three occupational groups with different training backgrounds

Computational modelling of patient specific spring assisted lambdoid craniosynostosis correction

Lambdoid craniosynostosis (LC) is a rare non-syndromic craniosynostosis characterised by fusion of the lambdoid sutures at the back of the head. Surgical correction including the spring assisted cranioplasty is the only option to correct the asymmetry at the skull in LC. However, the aesthetic outcome from spring assisted cranioplasty may remain suboptimal. The aim of this study is to develop a parametric finite element (FE) model of the LC skulls that could be used in the future to optimise spring surgery. The skull geometries from three different LC patients who underwent spring correction were reconstructed from the pre-operative computed tomography (CT) in Simpleware ScanIP. Initially, the skull growth between the pre-operative CT imaging and surgical intervention was simulated using MSC Marc. The osteotomies and spring implantation were performed to simulate the skull expansion due to the spring forces and skull growth between surgery and post-operative CT imaging in MSC Marc. Surface deviation between the FE models and post-operative skull models reconstructed from CT images changed between ± 5 mm over the skull geometries. Replicating spring assisted cranioplasty in LC patients allow to tune the parameters for surgical planning, which may help to improve outcomes in LC surgeries in the future

Intracranial volume measurement: A systematic review and comparison of different techniques

The ability to calculate intracranial volume (ICV) from 3-dimensional imaging is a useful tool in a craniofacial team's armamentarium. Intracranial volume uses range from decision making to assessment. Various methods to calculate ICV exist including fully manual, semiautomatic, and fully automatic techniques and they are used with varying frequency in craniofacial centres globally.This study aimed to systematically analyze and compare ICV calculations across the 3 methods and provide information to allow the reader to utilize these processes in practice.Twenty-six computed tomography scans from Apert patients were used to compare ICV measurements calculated using the following techniques: fully manual segmentation with OsiriX (taken as the gold standard); semiautomatic segmentation using Simpleware ScanIP; and fully automatic segmentation using FSL neuroimaging software. In addition, to assess the effect that a reducing CT scan slice number had on ICV measurement, 13 scans were remeasured using half, quarter, and an eighth of the slices of the full scan.The manual and semiautomatic techniques had intraclass correlation coefficients of 0.997, and 0.993 respectively. Intracranial volume measurements using the semi- and fully automatic techniques showed high linear correlation with manual techniques (R = 0.993 and R = 0.995). The coefficients of determination for full scan versus half, quarter, and eighth scan were R = 0.98, 0.96, and 0.94 respectively.Similar ICV results can be obtained using manual, semiautomatic, or automatic techniques with decreasing amount of time required to perform each method. Command line code for the fully automatic method is provided

Three-dimensional surface scanners compared with standard anthropometric measurements for head shape

Three-dimensional (3D) surface imaging devices designed to capture and quantify craniofacial surface morphology are becoming more common in clinical environments. Such scanners overcome the limitations of two-dimensional photographs while avoiding the ionizing radiation of computed tomography. The purpose of this study was to compare standard anthropometric cranial measurements with measurements taken from images acquired with 3D surface scanners.Two 3D scanners of different cost were used to acquire head shape data from thirteen adult volunteers: M4D scan and Structure Sensor. Head circumference and cephalic index were measured directly on the patients as well as on 3D scans acquired with the two scanners. To compare head volume measurements with a gold standard, magnetic resonance imaging scans were used. Repeatability and accuracy of both devices were evaluated.Intra-rater repeatability for both scanners was excellent (intraclass correlation coefficients > 0.99, p < 0.001). Direct and digital measures of head circumference, cephalic index and head volume were strongly correlated (0.85 < . r < 0.91, p < 0.001). Compared to direct measurements, accuracy was highest for M4D scan.Both 3D scanners provide reproducible data of head circumference, cephalic index and head volume and show a strong correlation with traditional measurements. However, care must be taken when using absolute values

Assessment of spring cranioplasty biomechanics in sagittal craniosynostosis patients

OBJECTIVE Scaphocephaly secondary to sagittal craniosynostosis has been treated in recent years with spring-assisted cranioplasty, an innovative approach that leverages the use of metallic spring distractors to reshape the patient skull. In this study, a population of patients who had undergone spring cranioplasty for the correction of scaphocephaly at the Great Ormond Street Hospital for Children was retrospectively analyzed to systematically assess spring biomechanical performance and kinematics in relation to spring model, patient age, and outcomes over time. METHODS Data from 60 patients (49 males, mean age at surgery 5.2 ± 0.9 months) who had received 2 springs for the treatment of isolated sagittal craniosynostosis were analyzed. The opening distance of the springs at the time of insertion and removal was retrieved from the surgical notes and, during the implantation period, from planar radiographs obtained at 1 day postoperatively and at the 3-week follow-up. The force exerted by the spring to the patient skull at each time point was derived after mechanical testing of each spring model-3 devices with the same geometry but different wire thicknesses. Changes in the cephalic index between preoperatively and the 3-week follow-up were recorded. RESULTS Stiffer springs were implanted in older patients (p < 0.05) to achieve the same opening on-table as in younger patients, but this entailed significantly different-higher-forces exerted on the skull when combinations of stiffer springs were used (p < 0.001). After initial force differences between spring models, however, the devices all plateaued. Indeed, regardless of patient age or spring model, after 10 days from insertion, all the devices were open. CONCLUSIONS Results in this study provide biomechanical insights into spring-assisted cranioplasty and could help to improve spring design and follow-up strategy in the future

Validation of an in-silico modelling platform for outcome prediction in spring assisted posterior vault expansion

BACKGROUND: Spring-Assisted Posterior Vault Expansion has been adopted at Great Ormond Street Hospital for Children, London, UK to treat raised intracranial pressure in patients affected by syndromic craniosynostosis, a congenital calvarial anomaly which causes premature fusion of skull sutures. This procedure aims at normalising head shape and augmenting intracranial volume by means of metallic springs which expand the back portion of the skull. The aim of this study is to create and validate a 3D numerical model able to predict the outcome of spring cranioplasty in patients affected by syndromic craniosynostosis, suitable for clinical adoption for preoperative surgical planning. METHODS: Retrospective spring expansion measurements retrieved from x-ray images of 50 patients were used to tune the skull viscoelastic properties for syndromic cases. Pre-operative computed tomography (CT) data relative to 14 patients were processed to extract patient-specific skull shape, replicate surgical cuts and simulate spring insertion. For each patient, the predicted finite element post-operative skull shape model was compared with the respective post-operative 3D CT data. FINDINGS: The comparison of the sagittal and transverse cross-sections of the simulated end-of-expansion calvaria and the post-operative skull shapes extracted from CT images showed a good shape matching for the whole population. The finite element model compared well in terms of post-operative intracranial volume prediction (R2 = 0.92, p < 0.0001). INTERPRETATION: These preliminary results show that Finite Element Modelling has great potential for outcome prediction of spring assisted posterior vault expansion. Further optimisation will make it suitable for clinical deployment

Cranial bone structure in children with sagittal craniosynostosis: Relationship with surgical outcomes

BACKGROUND: Whilst spring-assisted cranioplasty has become a widespread technique to correct scaphocephaly in children with sagittal synostosis, predicting head shape changes induced by the gradual opening of the springs remains challenging. The aim of this study was to explore the role of cranial bone structure on surgical outcomes. METHODS: Patients with isolated sagittal synostosis undergoing spring-assisted cranioplasty at GOSH (London, UK) were recruited (n=18, age: 3-8 months). Surgical outcome was assessed by the change in cephalic index measured on 3D head scans acquired before spring insertion and after their removal using a 3D handheld scanner. Parietal bone samples routinely discarded during spring-assisted cranioplasty were collected and scanned using micro-computed tomography. Based upon visual assessment of such scans, bone structure was classified into one- or three-layered, the latter indicating the existence of a diploё cavity. Bone average thickness, volume fraction and surface density were computed and correlated with changes in cephalic index. RESULTS: Cephalic index increased for all patients (p<0.001), but individual improvement varied. While the patient age and treatment duration were not significantly correlated with changes in cephalic index, bone structural parameters were. The increase of cephalic index was smaller with increasing bone thickness (Pearson’s r =-0.79, p<0.001) and decreasing bone surface density (r=0.77, p<0.001), associated with the three-layered bone structure. CONCLUSIONS: Variation in parietal bone micro-structure was associated with the magnitude of head shape changes induced by spring-assisted cranioplasty. This suggests that bone structure analysis could be a valuable adjunct in designing surgical strategies that yield optimal patient-specific outcomes