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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 cm 3and in the Pro253Arg group was 1115.8 cm 3(P=1.00). There was a significant increase in ICV following SA-PVE in all patients (P

OBJECTIVE Endoscopic strip craniectomy with postoperative helmet orthosis therapy (ESCH) has emerged as a less invasive alternative to fronto-orbital remodeling for correction of trigonocephaly. However, there is no standardized objective method for monitoring morphological changes following ESCH. Such a method should be reproducible and avoid the use of ionizing radiation and general anesthesia for diagnostic imaging. The authors analyzed a number of metrics measured using 3D stereophotogrammetry (3DSPG) following ESCH, an imaging alternative that is free of ionizing radiation and can be performed on awake children. METHODS 3DSPG images obtained at two time points (perisurgical and 1-year follow-up [FU]) of children with metopic synostosis who had undergone ESCH were analyzed and compared to 3DSPG images of age-matched control children without craniofacial anomalies. In total, 9 parameters were measured, the frontal angle and anteroposterior volume in addition to 7 novel parameters: anteroposterior area ratio, anteroposterior width ratios 1 and 2, and right and left anteroposterior diagonal ratios 30 and 60. RESULTS Six eligible patients were identified in the operated group, and 15 children were in the control group. All 9 parameters differed significantly between perisurgical and age-matched controls, as well as from perisurgical to FU scans. Comparison of FU scans of metopic synostosis patients who underwent surgery to scans of age-matched controls without metopic synostosis revealed that all parameters were statistically identical, with the exception of the right anteroposterior diagonal ratio 30, which was not fully corrected in the treated patients. The left anterior part of the head showed the most change in surface area maps. CONCLUSIONS In this pilot study, ESCH showed satisfactory results at 1 year, with improvements in all measured parameters compared to perisurgical results and normalization of 8 of 9 parameters compared to an age-matched control group. The results indicate that these parameters may be useful for craniofacial units for monitoring changes in head shape after ESCH for trigonocephaly and that 3DSPG, which avoids the use of anesthesia and ionizing radiation, is a satisfactory monitoring method.

Atlantoaxial rotatory fixation (AARF) is a rare condition that occurs most commonly in children. The torticollis caused by AARF usually presents as abnormal posturing of the head and neck, with rotation of the chin to the opposite side. AARF in children could occur due to congenital bony malformation, minor trauma, upper respiratory tract infections (Grisel's syndrome), postoperatively after head and neck (ENT) surgery, and unknown reasons. AARF in the postoperative patient is a rare and poorly understood entity.The authors present a case report of a 2-year-old boy with Crouzon Syndrome undergoing posterior calvarial vault expansion (PVE) surgery that developed AARF as a complication.The authors believe that cranial vault surgery should be considered a potential risk procedure for AARF, especially if it is done in susceptible populations (syndromic craniosynostosis patients) with other underlying sequelae (tonsillar ectopia or syringomyelia). During surgery, careful attention should be paid to maintaining a neutral alignment of the patient's cervical spine as rotatory movements under anaesthesia and muscle relaxation may be contributory factors.AARF should be suspected and investigated in children with painful torticollis after craniofacial surgery.

Aims To assess the diagnostic accuracy of fundoscopy and visual evoked potentials (VEPs) in detecting intracranial hypertension (IH) in patients with craniosynostosis undergoing spring-assisted posterior vault expansion (sPVE). Methods Children with craniosynostosis undergoing sPVE and 48-hour intracranial pressure (ICP) monitoring were included in this single-centre, retrospective, diagnostic accuracy study. Data for ICP, fundoscopy and VEPs were analysed. Primary outcome measures were papilloedema on fundoscopy, VEP assessments and IH, defined as mean ICP > 20 mmHg. Diagnostic indices were calculated for fundoscopy and VEPs against IH. Secondary outcome measures included final visual outcomes. Results Fundoscopic examinations were available for 35 children and isolated VEPs for 30 children, 22 of whom had at least three serial VEPs. Sensitivity was 32.1% for fundoscopy (95% confidence intervals [CI]: 15.9–52.4) and 58.3% for isolated VEPs (95% CI 36.6–77.9). Specificity for IH was 100% for fundoscopy (95% CI: 59.0–100) and 83.3% for isolated VEPs (95% CI: 35.9–99.6). Where longitudinal deterioration was suspected from some prVEPs but not corroborated by all, sensitivity increased to 70.6% (95% CI: 44.0–89.7), while specificity decreased to 60% (95% CI: 14.7–94.7). Where longitudinal deterioration was clinically significant, sensitivity decreased to 47.1% (23.0–72.2) and specificity increased to 100% (47.8–100). Median final BCVA was 0.24 logMAR (n = 36). UK driving standard BCVA was achieved by 26 patients (72.2%), defined as ≥0.30 logMAR in the better eye. Conclusion Papilloedema present on fundoscopy reliably indicated IH, but its absence did not exclude IH. VEP testing boosted sensitivity at the expense of specificity, depending on method of analysis.

Purpose Children affected by premature fusion of the cranial sutures due to craniosynostosis can present with raised intracranial pressure and (turri)brachycephalic head shapes that require surgical treatment. Spring-assisted posterior vault expansion (SA-PVE) is the surgical technique of choice at Great Ormond Street Hospital for Children (GOSH), London, UK. This study aims to report the SA-PVE clinical experience of GOSH to date. Methods A retrospective review was carried out including all SA-PVE cases performed at GOSH between 2008 and 2020. Demographic and clinical data were recorded including genetic diagnosis, craniofacial surgical history, surgical indication and assessment, age at time of surgery (spring insertion and removal), operative time, in-patient stay, blood transfusion requirements, additional/secondary (cranio)facial procedures, and complications. Results Between 2008 and 2020, 200 SA-PVEs were undertaken in 184 patients (61% male). The study population consisted of patients affected by syndromic (65%) and non-syndromic disorders. Concerns regarding raised intracranial pressure were the surgical driver in 75% of the cases, with the remainder operated for shape correction. Median age for SA-PVE was 19 months (range, 2–131). Average operative time for first SA-PVE was 150 min and 87 for spring removal. Median in-patient stay was 3 nights, and 88 patients received a mean of 204.4 ml of blood transfusion at time of spring insertion. A single SA-PVE sufficed in 156 patients (85%) to date (26 springs still in situ at time of this analysis); 16 patients underwent repeat SA-PVE, whilst 12 underwent rigid redo. A second SA-PVE was needed in significantly more cases when the first SA-PVE was performed before age 1 year. Complications occurred in 26 patients with a total of 32 events, including one death. Forty-one patients underwent fronto-orbital remodelling at spring removal and 22 required additional cranio(maxillo)facial procedures. Conclusions Spring-assisted posterior vault expansion is a safe, efficient, and effective procedure based on our 12-year experience. Those that are treated early in life might require a repeat SA-PVE. Long-term follow-up is recommended as some would require additional craniomaxillofacial correction later in life.

Patients with Apert syndrome experience midfacial hypoplasia, hypertelorism, and downslanting palpebral fissures which can be corrected by midfacial bipartition distraction with rigid external distraction device. Quantitative studies typically focus on quantifying rigid advancement and rotation postdistraction, but intrinsic shape changes of bone and soft tissue remain unknown. This study presents a method to quantify these changes. Pre- and post-operative computed tomography scans from patients with Apert syndrome undergoing midfacial bipartition distraction with rigid external distraction device were collected. Digital Imaging and Communications in Medicine files were converted to three-dimensional bone and soft tissue reconstructions. Postoperative reconstructions were aligned on the preoperative maxilla, followed by nonrigid iterative closest point transformation to determine local shape changes. Anatomical point-to-point displacements were calculated and visualized using a heatmap and arrow map. Nine patients were included.Zygomatic arches and frontal bone demonstrated the largest changes. Mid-lateral to supra-orbital rim showed an upward, inward motion. Mean bone displacements ranged from 3.3 to 12.8 mm. Soft tissue displacements were relatively smaller, with greatest changes at the lateral canthi. Midfacial bipartition distraction with rigid external distraction device results in upward, inward rotation of the orbits, upward rotation of the zygomatic arch, and relative posterior motion of the frontal bone. Local movements were successfully quantified using a novel method, which can be applied to other surgical techniques/syndromes.

OBJECTIVESThe goal of this study was to characterize the complications and morbidity related to the surgical management of pediatric fourth ventricle tumors.METHODSAll patients referred to the authors’ institution with posterior fossa tumors from 2002 to 2018 inclusive were screened to include only true fourth ventricle tumors. Preoperative imaging and clinical notes were reviewed to extract data on presenting symptoms; surgical episodes, techniques, and adjuncts; tumor histology; and postoperative complications.RESULTSThree hundred fifty-four children with posterior fossa tumors were treated during the study period; of these, 185 tumors were in the fourth ventricle, and 167 fourth ventricle tumors with full data sets were included in this analysis. One hundred patients were male (mean age ± SD, 5.98 ± 4.12 years). The most common presenting symptom was vomiting (63.5%). The most common tumor types, in order, were medulloblastoma (94 cases) > pilocytic astrocytoma (30 cases) > ependymoma (30 cases) > choroid plexus neoplasms (5 cases) > atypical teratoid/rhabdoid tumor (4 cases), with 4 miscellaneous lesions. Of the 67.1% of patients who presented with hydrocephalus, 45.5% had an external ventricular drain inserted (66.7% of these prior to tumor surgery, 56.9% frontal); these patients were more likely to undergo ventriculoperitoneal shunt (VPS) placement at a later date (p = 0.00673). Twenty-two had an endoscopic third ventriculostomy, of whom 8 later underwent VPS placement. Overall, 19.7% of patients had a VPS sited during treatment.Across the whole series, the transvermian approach was more frequent than the telovelar approach (64.1% vs 33.0%); however, the telovelar approach was significantly more common in the latter half of the series (p < 0.001). Gross-total resection was achieved in 70.7%. The most common postoperative deficit was cerebellar mutism syndrome (CMS; 28.7%), followed by new weakness (24.0%), cranial neuropathy (18.0%), and new gait abnormality/ataxia (12.6%). Use of intraoperative ultrasonography significantly reduced the incidence of CMS (p = 0.0365). There was no significant difference in the rate of CMS between telovelar or transvermian approaches (p = 0.745), and multivariate logistic regression modeling did not reveal any statistically significant relationships between CMS and surgical approach.CONCLUSIONSSurgical management of pediatric fourth ventricle tumors continues to evolve, and resection is increasingly performed through the telovelar route. CMS is enduringly the major postoperative complication in this patient population.

OBJECTIVE Sagittal craniosynostosis (SC) is the most commonly encountered form of craniosynostosis. Despite its relative frequency, there remains significant heterogeneity in both operative management and follow-up between centers and a relative paucity of long-term outcome data in the literature. At the authors’ institution, families of children presenting with SC are offered the following options: 1) conservative management with ophthalmic surveillance, 2) minimally invasive surgery at < 6 months of age (spring-assisted cranioplasty [SAC]) or 3) calvarial vault remodeling at any age (CVR). The authors reviewed outcomes for all children presenting with SC during a 5-year period, regardless of the treatment received. METHODS Consecutive children born between January 1, 2008, and December 31, 2012, presenting with SC were identified, and detailed chart reviews were undertaken. Demographic, surgical, perioperative, head shape, scar, and neurodevelopmental (behavioral, education, speech, and language) data were analyzed. The cohort was divided by type of surgery (none, SAC, or CVR) and by age at surgery (early, defined as ≤ 6 months; or late, defined as > 6 months) for comparison purposes. RESULTS A total of 167 children were identified, 129 boys and 38 girls, with a median age at presentation of 5.0 (range 0.4–135) months. Three families opted for conservative management. Of the 164 children who underwent surgery, 83 underwent SAC, 76 underwent CVR, and 5 underwent a "hybrid" procedure (CVR with springs). At a median age of 7.0 (range 0.5–12.3) years, there was no significant difference in concerns regarding head shape, scar, or neurodevelopmental outcomes between the early and late intervention groups over all procedures performed, or between the early or late SAC and CVR cohorts. There were more head shape concerns in the SAC group than in the CVR group overall (25.7% vs 11.8%, respectively; p = 0.026), although most of these concerns were minor and did not require revision. CONCLUSIONS In this cohort, regardless of operative intervention and timing of intervention, infants achieved similar neurodevelopmental outcomes. Minimally invasive surgery (SAC) appears to result in less complete correction of head shape than CVR, but this may be balanced by advantages in reduced operative time, hospitalization, and blood loss. SAC was equal to CVR in neuropsychological outcomes.

Endoscopic suturectomy with postoperative helmeting (ESCH) has emerged as a successful treatment for craniosynostosis, initially in North America. We report early outcomes from the first cohort of ESCH patients treated in the United Kingdom (UK).

Spring-assisted cranioplasty (SAC) is a minimally invasive technique for treating sagittal synostosis in young infants. Yet, follow-up data on cranial growth in patients who have undergone SAC are lacking. This project aimed to understand how the cranial shape develops during the postoperative period, from spring insertion to removal. 3D head scans of 30 consecutive infants undergoing SAC for sagittal synostosis were acquired using a handheld scanner pre-operatively, immediately postoperatively, at follow-up and at spring removal; 3D scans of 41 age-matched control subjects were also acquired. Measurements of head length, width, height, circumference, and volume were taken for all subjects; cephalic index (CI) was calculated. Statistical shape modeling was used to compute 3D average head models of sagittal patients at the different time points. SAC was performed at a mean age of 5.2 months (range 3.3-8.0) and springs were removed 4.3 months later. CI increased significantly (P < 0.001) from pre-op (69.5% ± 2.8%) to spring removal (74.4% ± 3.9%), mainly due to the widening of head width, which became as wide as for age-matched controls; however, the CI of controls was not reached (82.3% ± 6.8%). The springs did not constrain volume changes and allowed for natural growth. Population mean shapes showed that the bony prominences seen at the sites of spring engagement settle over time, and that springs affect the overall 3D head shape of the skull. In conclusion, results reaffirmed the effectiveness of SAC as a treatment method for nonsyndromic single suture sagittal synostosis.

Supplemental Digital Content is available in the text, Objective: Craniosynostosis can be associated with raised intracranial pressure (ICP), which can pose deleterious effects on the brain and vision if untreated. Estimating ICP in children is challenging, whilst gold standard direct intracranial measurement of ICP is invasive and carries risk. This systematic review aims to evaluate the role of optical coherence tomography (OCT), a noninvasive imaging technique, for detecting raised ICP in children with craniosynostosis. Methods: The authors conducted a systematic review of the literature published from inception until 19 August, 2019 in the Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, and EMBASE. Eligible studies evaluated the role of OCT in detecting raised ICP in children aged 0 to 16 years with craniosynostosis. Main outcome measures were sensitivity and specificity of OCT parameters for raised ICP. Quality assessment was performed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. Results: Out of 318 records identified, data meeting the inclusion criteria were obtained from 3 studies. The quality of 2 studies was poor whilst 1 was fair. Optical coherence tomography demonstrated higher sensitivity and specificity for detecting raised ICP compared to fundus examination, clinical history, radiological testing, and visual field testing. Conclusions: This systematic review demonstrated a lack of quality evidence for OCT as a screening tool for children with craniosynostosis. Further research is required to clarify the strength of OCT in this role and to determine which OCT parameters are most appropriate.

Unicoronal craniosynostosis is the second most common type of nonsyndromic craniosynostosis: it is characterized by ipsilateral forehead and fronto-parietal region flattening with contralateral compensatory bossing. It is a complex condition; therefore, which is difficult to treat because of the asymmetry in the orbits, cranium, and face. The aim of this study is to understand optimal osteotomy locations, dimensions, and force requirements for surgical operations of unicoronal craniosynostosis using a patient-specific finite element model and - at the same time - to evaluate the potential application of a new device made from Nitinol which was developed to expand the affected side of a unicoronal craniosynostosis skull without performing osteotomies. The model geometry was reconstructed using Simpleware ScanIP. The bone and sutures were modeled using elastic properties to perform the finite element analyses in MSc Marc software. The simulation results showed that expanding the cranium without osteotomy requires a significant amount of force. Therefore, expansion of the cranium achieved by Nitinol devices may not be sufficient to correct the deformity. Moreover, the size and locations of the osteotomies are crucial for an optimal outcome from surgical operations in unicoronal craniosynostosis.

OBJECTIVE Endoscopic strip craniectomy with postoperative molding helmet therapy (ESC-H) and spring-assisted cranioplasty (SAC) are commonly used minimally invasive techniques for correction of nonsyndromic sagittal craniosynostosis, but it is unclear which, if either, is superior. Therefore, the authors undertook a systematic review to compare ESC-H with SAC for the surgical management of nonsyndromic single-suture sagittal craniosynostosis. METHODS Studies were identified through a systematic and comprehensive search of four databases (Embase, MEDLINE, and two databases in the Cochrane Library). Databases were searched from inception until February 19, 2021. Pediatric patients undergoing either ESC-H or SAC for the management of nonsyndromic single-suture sagittal craniosynostosis were included. Systematic reviews and meta-analyses, single-patient case reports, mixed cohorts of nonsyndromic and syndromic patients, mixed cohorts of different craniosynostosis types, and studies in which no outcomes of interest were reported were excluded. Outcomes of interest included reoperations, blood transfusion, complications, postoperative intensive care unit (ICU) admission, operative time, estimated blood loss, length of hospital stay, and cephalic index. Pooled summary cohort characteristics were calculated for each outcome of interest. Methodological quality was assessed using the Newcastle-Ottawa Scale. The study was reported in accordance with the 2020 PRISMA statement. RESULTS Twenty-two studies were eligible for inclusion in the review, including 1094 patients, of whom 605 (55.3%) underwent ESC-H and 489 (44.7%) underwent SAC for nonsyndromic sagittal craniosynostosis. There was no difference between the pooled estimates of the ESC-H and SAC groups for operative time, length of stay, estimated blood loss, and cephalic index. There was no difference between the groups for reoperation rate and complication rate. However, ESC-H was associated with a higher blood transfusion rate and higher postoperative ICU admission. CONCLUSIONS The available literature does not demonstrate superiority of either ESC-H or SAC, and outcomes are broadly similar for the treatment of nonsyndromic sagittal craniosynostosis. However, the evidence is limited by single-center retrospective studies with low methodological quality. There is a need for international multicenter randomized controlled trials comparing both techniques to gain definitive and generalizable data.

IntroductionPaediatric intracranial hypertension (IH) is a rare but serious condition that can pose deleterious effects on the brain and vision. Estimating intracranial pressure (ICP) in children is difficult. Gold standard direct ICP measurement is invasive and carries risk. It is impractical to routinely perform direct ICP measurements over time for all children at risk of IH. This study proposes to assess the diagnostic accuracy of handheld optical coherence tomography (OCT), a non-invasive ocular imaging method, to detect IH in children.Methods and analysisThis is a prospective study evaluating the diagnostic accuracy of handheld OCT for IH in at risk children. Inclusion criteria include clinical and/or genetic diagnosis of craniosynostosis, idiopathic intracranial hypertension, space occupying lesion or other conditions association with IH and age 0–18 years old. Exclusion criteria include patients older than 18 years of age and/or absence of condition placing the child at risk of IH. The primary outcome measures are handheld OCT and 48-hour ICP assessments, which will be used for diagnostic accuracy testing (sensitivity, specificity, positive predictive value, negative predictive value and accuracy). Main secondary outcome measures include visual acuity, fundoscopic examination, contrast sensitivity, visual field testing and visual evoked potentials, wherever possible.Ethics and disseminationEthical approval was granted for this study by the East Midlands Nottingham 2 Research Ethics committee (UOL0348/IRAS 105137). Our findings will be disseminated through presentation at relevant meetings, peer-reviewed publication and via the popular media.Trial registration numberISRCTN52858719

The aim of the study was to investigate whether different head shapes show different volumetric changes following spring-assisted posterior vault expansion (SA-PVE) and to investigate the influence of surgical and morphological parameters on SA-PVE. Preoperative three-dimensional skull models from patients who underwent SA-PVE were extracted from computed tomography scans. Patient head shape was described using statistical shape modelling (SSM) and principal component analysis (PCA). Preoperative and postoperative intracranial volume (ICV) and cranial index (CI) were calculated. Surgical and morphological parameters included skull bone thickness, number of springs, duration of spring insertion and type of osteotomy. In the analysis, 31 patients were included. SA-PVE resulted in a significant ICV increase (284.1 ± 171.6 cm3, p < 0.001) and a significant CI decrease (-2.9 ± 4.3%, p < 0.001). The first principal component was significantly correlated with change in ICV (Spearman ρ = 0.68, p < 0.001). Change in ICV was significantly correlated with skull bone thickness (ρ = -0.60, p < 0.001) and age at time of surgery (ρ = -0.60, p < 0.001). No correlations were found between the change in ICV and number of springs, duration of spring insertion and type of osteotomy. SA-PVE is effective for increasing the ICV and resolving raised intracranial pressure. Younger, brachycephalic patients benefit more from surgery in terms of ICV increase. Skull bone thickness seems to be a crucial factor and should be assessed to achieve optimal ICV increase. In contrast, insertion of more than two springs, duration of spring insertion or performing a fully cut through osteotomy do not seem to impact the ICV increase. When interpreting ICV increases, normal calvarial growth should be taken into account.

Background This study aims to capture the 3D shape of the human skull in a healthy paediatric population (0–4 years old) and construct a generative statistical shape model. Methods The skull bones of 178 healthy children (55% male, 20.8 ± 12.9 months) were reconstructed from computed tomography (CT) images. 29 anatomical landmarks were placed on the 3D skull reconstructions. Rotation, translation and size were removed, and all skull meshes were placed in dense correspondence using a dimensionless skull mesh template and a non-rigid iterative closest point algorithm. A 3D morphable model (3DMM) was created using principal component analysis, and intrinsically and geometrically validated with anthropometric measurements. Synthetic skull instances were generated exploiting the 3DMM and validated by comparison of the anthropometric measurements with the selected input population. Results The 3DMM of the paediatric skull 0–4 years was successfully constructed. The model was reasonably compact - 90% of the model shape variance was captured within the first 10 principal components. The generalisation error, quantifying the ability of the 3DMM to represent shape instances not encountered during training, was 0.47 mm when all model components were used. The specificity value was, Highlights • 3D morphable model of the paediatric skull (0–4 years) was created from 178 CT scans. • The model was validated using compactness, generalisation and specificity. • Validation experiments demonstrated that the model can produce realistic novel skull samples. • Skull shape was shown to be a good indicator of age for the study population. • Gender was not shown to play a role in skull shape for the study population.

BACKGROUND: Paediatric High Grade Gliomas (HGG) have poor outcomes with conventional treatment. HGG in association with constitutional DNA mismatch repair deficiency (CMMRD) are hypermutated and have shown dramatic response to checkpoint inhibitors. Salvage following progression or failure to respond to check point inhibitors has rarely been reported. We describe a successful alternative therapeutic approach targeting the activated pathway (mTOR) in a hypermutated HGG. CASE SUMMARY: A 6-year-old girl presenting with seizures was diagnosed with left frontal lobe HGG with concurrent neck mass (Pilomatrixoma). Presence of synchronous tumours raised the possibility of cancer predisposition; the HGG was hypermutated with germline PMS2 mutation confirming diagnosis of CMMRD. Near total resection was undertaken followed by focal radiotherapy 54 Gy, with 1 cycle of concomitant CCNU. MRI post radiotherapy showed tumour progression. Anti-PDl inhibitor Nivolumab was commenced. CTLA-4 antibody, Ipilimumab was added after 4 cycles of Nivolumab due to poor response. Tumour response was seen, but dual therapy had to be discontinued due to toxicity. The tumour progressed following further single agent Nivolumab. In view of multiple mutations in the mTOR pathway (NF1, PIK3/PTEN, TSC1, TSC2), a mTOR inhibitor, Everolimus was commenced. There was 25% tumour reduction after 4 weeks treatment and further reduction after 6 months. Resection of residual tumour showed necrotic tissue only. There continues to be a sustained response to Everolimus for over 12 months. DISCUSSION: Approximately a third of CMMRD HGG respond to checkpoint inhibitors. For those that don’t, these hypermutated tumours offers the possibility of targeting specific molecular pathways. Response to Everolimus in HGG harbouring mTOR aberrations have been described. To our knowledge this is the first report of successful use of mTOR inhibitor in CMMRD HGG. CONCLUSION: Targeted molecular treatment for patients with CMMRD hypermutated brain tumours should be considered according to the mutated pathways.

Management of infant medulloblastoma remains a challenge. Front-line chemotherapy can successfully avoid radiation in low-risk infant medulloblastoma. Patients that do relapse can be salvaged long-term with radiotherapy. We report 4 cases of infants with medulloblastoma treated with chemotherapy (HIT2000 protocol) with residual or progressive disease. RESULTS: Four cases of infant medulloblastoma, all MBEN/nodular desmoplastic SHH type B, p53 WT, no MYC / MYCN amplification. CASE 1: 16 month old girl, metastatic lesions in the cerebellum and meningeal enhancement. Germline SUFU mutation. After 3 cycles of chemotherapy MRI showed more enhancement of the residual disease. To inform management, second look surgery was performed. Pathology showed fibrous tissue only, no malignant cells. The child continues to be treated as per HIT2000. CASE 2: 5 month old girl, metastatic lesions in the cerebellum. Germline SUFU mutation. 2 months after end of treatment, MRI demonstrated progression of cerebellar lesion. Surgical resection was performed, pathology showed differentiated mature neuronal tissue. No further treatment; remains in remission 1 year after suspected progression. CASE 3: 27 month old boy, metastatic lesions in cerebellum. Germline SUFU mutation. 1 month post-completion of treatment progressive prominent nodules along the cerebellum and cerebellar leptomeningeal enhancement. Biopsy not feasible so close MRI surveillance was initiated. MRI remains stable 1 year after suspected progression. CASE 4: 30 months old boy, non-metastatic disease. Complete resection. No germline mutation. End-of-treatment MRI showed subtle new intraspinal leptomeningeal deposits and a suspicious left optic tract nodule, subsequent MRI 8 weeks later showed clear progressive disease. Unfortunately, the child died before radiotherapy could be delivered. CONCLUSION: Salvage radiotherapy for infants with medulloblastoma who progress following chemotherapy treatment can be life-saving but risk significant cognitive impairment. Differentiation of medulloblastoma following radio/chemotherapy has been reported. We recommend considering tissue confirmation prior to embarking on further treatment for suspected relapse.

Purpose To determine whether handheld optical coherence tomography (OCT) is feasible and repeatable in children with craniosynostosis. Methods This was a prospective cross-sectional study. Children with syndromic and non-syndromic craniosynostosis 0 to 18 years of age were recruited between February 13, 2020, and October 1, 2020. Main outcome measures included feasibility (patient recruitment and handheld OCT success rates) and repeatability, which were assessed using intraclass correlation coefficients (ICCs) where repeated images of the optic nerve head (ONH) within the same visit were available. ONH parameters used for repeatability analysis included cup depth, width, and area; disc width; rim height; retinal thickness; retinal nerve fiber layer thickness; and Bruch's membrane opening minimum rim width. Results Fifty children were approached, and all 50 (100%) were successfully recruited. Median age was 51.1 months (range, 1.9-156.9; interquartile range, 37.0-74.2), and 33 of the children (66%) were male. At least one ONH image was obtained in 43 children (86%), and bilateral ONH imaging was successful in 38 children (76%). Factors boosting the likelihood of success included good understanding and cooperation of the child and parent/guardian and availability of an assistant. Repeatability analysis was performed in 20 children, demonstrating good repeatability (ICC range, 0.77-0.99; the majority exceeded 0.90). OCT correctly identified two cases of intracranial hypertension, one of which was undetected by prior fundoscopy. Conclusions Handheld OCT is feasible and repeatable in children with syndromic and non-syndromic forms of craniosynostosis. Translational relevance Our handheld OCT approach could be used for the clinical surveillance of children with craniosynostosis.

Sagittal craniosynostosis consists of premature fusion (ossification) of the sagittal suture during infancy, resulting in head deformity and brain growth restriction. Spring-assisted cranioplasty (SAC) entails skull incisions to free the fused suture and insertion of two springs (metallic distractors) to promote cranial reshaping. Although safe and effective, SAC outcomes remain uncertain. We aimed hereby to obtain and validate a skull material model for SAC outcome prediction. Computed tomography data relative to 18 patients were processed to simulate surgical cuts and spring location. A rescaling model for age matching was created using retrospective data and validated. Design of experiments was used to assess the effect of different material property parameters on the model output. Subsequent material optimization—using retrospective clinical spring measurements—was performed for nine patients. A population-derived material model was obtained and applied to the whole population. Results showed that bone Young’s modulus and relaxation modulus had the largest effect on the model predictions: the use of the population-derived material model had a negligible effect on improving the prediction of on-table opening while significantly improved the prediction of spring kinematics at follow-up. The model was validated using on-table 3D scans for nine patients: the predicted head shape approximated within 2 mm the 3D scan model in 80% of the surface points, in 8 out of 9 patients. The accuracy and reliability of the developed computational model of SAC were increased using population data: this tool is now ready for prospective clinical application.

Current computational tools for planning and simulation in plastic and reconstructive surgery lack sufficient precision and are time-consuming, thus resulting in limited adoption. Although computer-assisted surgical planning systems help to improve clinical outcomes, shorten operation time and reduce cost, they are often too complex and require extensive manual input, which ultimately limits their use in doctor-patient communication and clinical decision making. Here, we present the first large-scale clinical 3D morphable model, a machine-learning-based framework involving supervised learning for diagnostics, risk stratification, and treatment simulation. The model, trained and validated with 4,261 faces of healthy volunteers and orthognathic (jaw) surgery patients, diagnoses patients with 95.5% sensitivity and 95.2% specificity, and simulates surgical outcomes with a mean accuracy of 1.1 ± 0.3 mm. We demonstrate how this model could fully-automatically aid diagnosis and provide patient-specific treatment plans from a 3D scan alone, to help efficient clinical decision making and improve clinical understanding of face shape as a marker for primary and secondary surgery.

Introduction: Endoscopic strip craniectomy with helmeting (ESCH) has been shown to be a safe and efficacious alternative to fronto-orbital remodeling (FOR) for selected children with craniosynostosis. In addition to clinical factors, there may be economic benefits from the use of ESCH instead of FOR. Methods: A retrospective review of 23 patients with nonsyndromic unicoronal craniosynostosis (UCS) treated with FOR was carried out at Great Ormond Street Hospital (GOSH) for Children in London, UK. Secondary data were used for the ESCH cohort from a paper published by Jimenez and Barone (2013). Data were collected on surgical time, transfusion rates, length of hospital stay, adverse event rates, reintervention rates, and overall costs. Costs were categorized and then assigned to the appropriate data sets. Results: The mean age of patients undergoing FOR (vs. ESCH) was 17.4 mo (vs. 3.1 mo) with a mean surgical time of 234 min (vs. 55 min), mean transfusion volume of 221.6 mL (vs. 80.0 mL), mean transfusion rate of 14/23 (vs. 2/115), and a total immediate overnight stay of 3.13 days (vs. 97% next-day discharge). The FOR group had a higher adverse event rate (5/23 vs. 4/115, p=

Cranial lacunae (foci of attenuated calvarial bone) are CT equivalents of “copper beating” seen on plain skull radiographs in children with craniosynostosis. The qualitative presence of copper beating has not been found to be useful for the diagnosis of intracranial hypertension (IH) in these patients. 3D morphometric analysis (3DMA) allows a more systematic and quantitative assessment of calvarial attenuation. We used 3DMA to examine the relationship between cranial lacunae and IH in children with Crouzon and Apert syndromic craniosynostosis. Patients were divided into IH and non-IH groups defined on an intention-to-treat basis. Pre-operative CT scans were converted into 3D skull models and processed to quantify lacunae as a percentage of calvarium surface area (LCP). This was done on individual bone and whole skull basis. Eighteen consecutive children with Crouzon’s syndrome and 17 with Apert syndrome were identified. Median age at CT scan was 135 days (range 6–1778). Of the 35 children, 21 required surgery for IH at median age of 364 days (range 38–1710). Of these 21 children, 14 had lacunae with mean LCP of 3% (0–28%). Of the 14 non-IH children, 8 had lacunae with mean LCP of 2% (0–8%). LCP was not significantly different between IH and non-IH groups. Parietal bones were most likely to show lacunae (IH 14/21, non-IH 9/14), followed by occipital (IH 8/21, non-IH 3/14), and frontal (IH 6/21, non-IH 2/14). Results suggest that cranial lacunae, measured using quantitative 3DMA, do not correlate with IH, in agreement with evidence from qualitative plain skull radiograph studies.

Purpose Late deformity/indentation is well-recognised following fronto-orbital remodelling (FOR) for metopic synostosis. We hypothesise that if damage to temporalis muscle were a contributor, the thickness of soft tissue and bone in the affected area would be reduced. Materials and methods Soft tissues and bone were separately segmented and reconstructed three-dimensionally from computed tomograms of 8 patients 1.5–18 years post-FOR performed at 16 ± 2 months for metopic synostosis and from 8 age-matched controls. Soft tissue (taken as proxy for temporalis muscle) and bone thickness overall and in the indented areas were computed. Results Post-FOR, three-dimensional soft tissue thickness maps demonstrated temporalis extending upwards but falling short of the indented area. Overall skull thickness increased with age post-FOR (logarithmic fit R2 = 0.71) and for controls (R2 = 0.90). Although immediately post-FOR the future indented area had a thickness of 98% of control, it decreased linearly to 64% 16 years later (Pearson's r = 0.84). Conclusion These findings suggest that late post-FOR deformity/indentation is enhanced by limited upward extension (or retraction downwards) of temporalis muscle, while bone thickness in the affected area gradually decreases. This supports the hypothesis that aberrant re-attachment of the temporalis muscle makes a material contribution to late deformity following FOR for metopic synostosis.

Patients with syndromic craniosynostosis have a molecularly identified genetic cause for the premature closure of their cranial sutures and associated facial and extra-cranial features. Their clinical complexity demands comprehensive management by an extensive multidisciplinary team. This review aims to marry genotypic and phenotypic knowledge with clinical presentation and management of the craniofacial syndromes presenting most frequently to the craniofacial unit at Great Ormond Street Hospital for Children NHS Foundation Trust.

BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged