Nonsyndromic Craniosynostosis Patients Research Articles

Neurocognitive outcomes and associated clinical factors 5 years after surgery in children with craniosynostosis.

Craniosynostosis involves early closure of one or more sutures, which is known to limit normal cranium growth and interfere with normal brain development. Various surgical methods are used, ranging from minimally invasive strip craniectomy to more extensive whole-vault cranioplasty. This study aimed to evaluate neurocognitive outcomes 5 years after surgical treatment in children with craniosynostosis and to evaluate relevant clinical factors. After exclusion of genetically confirmed syndromic craniosynostosis patients, a retrospective review was conducted on 112 nonsyndromic craniosynostosis patients who underwent surgical treatment and follow-up neurocognitive assessment. Ninety-seven patients underwent strip craniectomy with postoperative orthotic helmet therapy, and 15 received other surgical treatment: 4 with distraction osteotomy and 11 with craniofacial reconstruction. Neurocognitive assessment using the Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), was performed 5 years postoperatively. Clinical factors were assessed regarding neurocognitive outcomes. The mean age at surgery was significantly younger in the strip craniectomy group (strip craniectomy 4.6 months vs other surgical treatment 18.6 months, p < 0.01). Patients with 2 or more sutures involved were more likely to receive more extensive surgical treatment (16.5% in the strip craniectomy group vs 53.8% in the other group, p < 0.01). Four (3.5%) patients who showed evidence of increased intracranial pressure (ICP) also underwent more extensive surgical treatment. Multivariable linear regression revealed a significant correlation of age at neurocognitive testing (-3.18, 95% CI -5.95 to -0.40, p = 0.02), increased ICP (-34.73, 95% CI -51.04 to -18.41, p < 0.01), and the level of maternal education (6.11, 95% CI 1.01-11.20, p = 0.02) with the Full-Scale Intelligence Quotient (FSIQ). Age at surgery, involvement of 2 or more sutures, and type of operation demonstrated no correlation with FSIQ. Among the 97 patients who underwent strip craniectomy, the FSIQ ranged from mean ± SD 100.2 ± 10.2 (bicoronal) to 110.1 ± 12.7 (lambdoid), and there was no significant difference between the suture groups (p = 0.41). The 5 index scores were all within average ranges based on their age norms. Age at neurocognitive assessment, increased ICP, and maternal education level showed significant correlations with the neurocognitive function of craniosynostosis patients. Although children with craniosynostosis exhibited favorable 5-year postoperative neurocognitive outcomes across various synostosis sutures, longer follow-up is needed to reveal the incidence of neurocognitive dysfunction in these patients.

A diffusion tensor imaging comparison of white matter development in nonsyndromic craniosynostosis to neurotypical infants.

Nonsyndromic craniosynostosis (NSC) is associated with neurocognitive deficits, and intervention at infancy is standard of care to limit the negative effects of NSC on brain development. In this study, diffusion tensor imaging (DTI) was implemented to investigate white matter microstructure in infants with NSC undergoing cranial vault remodeling, and a comparison was made with white matter development in neurotypical controls. Infants presenting with NSC (n = 12) underwent DTI scans before and after cranial vault remodeling. Neurotypical infants (n = 5), age matched to NSC patients at preoperative scans, were compared to preoperative DTI scans. Pre- and postoperative NSC scans were compared in aggregate, and the sagittal synostosis (n = 8) patients were evaluated separately. Finally, neurotypical infants from the University of North Carolina/University of New Mexico Baby Connectome Project (BCP), who underwent DTI scans at timepoints matching the NSC pre- and postoperative DTI scans, were analyzed (n = 9). Trends over the same time period were compared between NSC and BCP scans. No significant differences were found between preoperative NSC scans and controls. White matter development was more limited in NSC patients than in BCP patients, with microstructural parameters of the corpus body and genu and inferior and superior longitudinal fasciculi consistently lagging behind developmental changes observed in healthy patients. Infant white matter development appears more limited in NSC patients undergoing cranial vault remodeling relative to that in neurotypical controls. Further investigation is needed to explore these differences and the specific effects of early surgical intervention.

Integrated Endoscopic Craniosynostosis Surgery and Cranial Orthosis Program

Introduction: Craniosynostosis results from premature fusion of the cranial sutures. There has been a continuous evolution of surgical correction techniques from an extensive open procedure to the minimally invasive technique. Aims and Objectives: This novel surgical technique has never been previously done in the UAE and this article documents the experience of the first team to endoscopically correct craniosynostosis with planning, surgical techniques, and customized helmet therapy. Methods: A retrospective case series of 16 nonsyndromic craniosynostosis patients with unicoronal (6), sagittal (5), bicoronal (1), frontosphenoidal (2), and metopic craniosynostoses (2) was corrected endoscopically and followed up with customized cranial helmet. Preoperative and postoperative photography, along with anthropometric measurements were taken. Results: The mean age of all patients at the time of surgery was 101 (90–117) days, mean duration of surgery was 70 minutes (38–129), mean blood loss was 120 mL (100–150), and mean duration of hospital stay 4 days (4–5). No complications and mortality were reported. Mean number of helmets was 2 (1–3). Cranial index improved in all patients with sagittal and bicoronal craniosynostosis. Close cooperation with the orthotist ensured timely helmet therapy and accurate laser scanning documentation in head molding. Conclusions: This case series has demonstrated that endoscopically craniosynostosis correction is safe, effective, and reliable and is the first reported series from the Middle East. The authors believe that every patient with nonsyndromic single‑suture craniosynostosis should be offered endoscopic correction before the age of 6 months. The orthotist forms an important part of the Multi-disciplinary team, enabling successful outcomes.

Minor Suture Fusion is Associated With Chiari Malformation in Nonsyndromic Craniosynostosis.

Here, we focused on the association between minor suture fusion and Chiari malformation (CM) occurrence in nonsyndromic craniosynostosis (NSC), and evaluated how the minor suture affects the posterior cranial fossa by measuring the posterior fossa deflection angle (PFA). In this retrospective study, the clinical records of 137 patients who underwent surgery for NSC at Aichi Children's Health and Medical Center between April 2010 and May 2022 were analyzed. Clinical data from Aichi Developmental Disability Center Central Hospital was collected for 23 patients as the external validation set. Among the 137 patients, 123 were diagnosed with NSC and the remaining 14 with syndromic craniosynostosis. Of the 123 NSC patients, 23 patients presented with CM. Multivariate analysis showed that occipito-mastoid fusion was the only significant risk factor for CM ( P =0.0218). Within the NSC group, CM patients had a significantly increased PFA (6.33±8.10 deg) compared with those without CM (2.76±3.29 deg, P =0.0487). Nonsyndromic craniosynostosis patients with occipito-mastoid suture fusion had a significantly increased PFA (6.50±7.60 deg) compared with those without occipito-mastoid fusion (2.60±3.23 deg, P =0.0164). In the validation cohort, occipito-mastoid suture fusion was validated as an independent risk factor for CM in univariate analysis. Minor suture fusion may cause CM associated with NSC. Chiari malformation could develop due to an increased PFA due to minor suture fusion, which causes growth disturbance in the affected side and compensatory dilation in the contralateral side within the posterior cranial fossa.

Treatment Delays in Nonsyndromic Craniosynostosis: A 30-Year Retrospective Case-Control Analysis of the Impact of Socioeconomic and Family Status on Access to Care.

Patients with nonsyndromic craniosynostosis (NSC) generally undergo corrective surgery before 1 year of age to the mitigate morbidities and risks of delayed repair. The cohort of patients who receive primary corrective surgery after 1 year and factors associated with their gaps to care is poorly characterized in literature. A nested case-control study was conducted for NSC patients who underwent primary corrective surgery at our institution and affiliates between 1992 and 2022. Patients whose surgery occurred after 1 year of age were identified and matched 1:1 by surgical date to standard-care control subjects. Chart review was conducted to gather patient data regarding care timeline and sociodemographic characteristics. Odds of surgery after 1 year of age were increased in Black patients (odds ratio, 3.94; P < 0.001) and those insured by Medicaid (2.57, P = 0.018), with single caregivers (4.96, P = 0.002), and from lower-income areas (+1% per $1000 income decrease, P = 0.001). Delays associated with socioeconomic status primarily impacted timely access to a craniofacial provider, whereas caregiver status was associated with subspecialty level delays. These disparities were exacerbated in patients with sagittal and metopic synostosis, respectively. Patients with multisuture synostosis were susceptible to significant delays related to familial strain (foster status, insurer, and English proficiency). Patients from socioeconomically strained households face systemic barriers to accessing optimal NSC care; disparities may be exacerbated by the diagnostic/treatment complexities of specific types of craniosynostosis. Interventions at primary care and craniofacial specialist levels can decrease health care gaps and optimize outcomes for vulnerable patients.

Sex Differences in Comorbidities of Pediatric Craniosynostosis at Presentation

Introduction: Craniosynostosis is a common pediatric presentation in which the premature fusion of one or more cranial sutures results in a misshapen skull. This birth defect is often associated with comorbidities due to structural impacts on nearby anatomical features. While there is some evidence for a male predominance among craniosynostosis patients, little has been investigated regarding sex differences in comorbidities of this condition. This study seeks to explore potential sexual dimorphisms in craniosynostosis patients at the time of presentation. Methods: We conducted a retrospective, cross-sectional review of male and female non-syndromic craniosynostosis (NSC) patients between the ages of 1 month and 9 years that were evaluated at a 500-bed academic hospital or a 977-bed private hospital in Lubbock, TX, USA. Common comorbidities including ophthalmologic diagnoses, developmental delays, obstructive sleep apnea, chronic otitis media, hearing loss, chronic headaches, and seizure disorders were evaluated. The NSC cohort was compared to a similarly aged trauma group that represented the normal population. Results: 175 NSC patients fit the inclusion criteria, of which 109 (62%) were male. A diagnosis of craniosynostosis was significantly associated with ophthalmological diagnoses (p < 0.0001), chronic otitis media (p < 0.0001), developmental delays (p < 0.0001), and hearing loss (p = 0.0047). Male NSC patients were less likely to present with ophthalmological diagnoses (p = 0.0010) or hearing loss (p = 0.0052) than females. Conclusions: Our findings expand on current literature evaluating possible comorbidities of NSC, particularly supporting the association with ophthalmological diagnoses, chronic otitis media, developmental delays, and hearing loss. We also report sex differences in ophthalmological diagnoses and hearing loss for NSC patients. These findings can serve to educate physicians of symptoms requiring prompt recognition and management in these patients.

P83. LATE PRESENTATION OF NON-SYNDROMIC CRANIOSYNOSTOSIS: DOES SOCIOECONOMIC STATUS MATTER?

PURPOSE: Non-syndromic craniosynostosis (NSC) patients can be treated before 12 months of age to attenuate difficulties associated with delayed care (e.g. more challenging/extensive surgery, greater risk of complications). NSC patients that undergo delayed treatment are not well characterized in the literature. This study aims to identify potential contributors to delayed care for late presenting (>12 months of age at primary surgery) NSC patients. METHODS: A retrospective review of patients who underwent primary surgery for late presenting NSC at a single institution. Data including ages at diagnosis and surgery, clinical features, and sociodemographic variables such as home zip code median household income (MHI) were analyzed. RESULTS: Eighty-three patients were included, with a median age at surgery of 580 days. Of these, 32 (39%) were diagnosed before 12 months of age. Black, Hispanic, and “other” races had a greater, though not significant, average time to surgery than White or Asian patients (p = 0.062). MHI ranged from $20,636-140,511 (median = $45,584), with a 100-day delay in surgery associated with each $10,000 decrease in MHI (p = 0.040). Suture involvement was not associated with surgical delay. CONCLUSION: The association between surgical delay and decreased MHI suggests that socioeconomic disparities may contribute to care gaps in late presenting NSC patients; anticipation of these characteristics can help surgeons in patient identification and management.

Genetic Influence on Neurodevelopment in Nonsyndromic Craniosynostosis.

Nonsyndromic craniosynostosis is one of the most common anomalies treated by craniofacial surgeons. Despite optimal surgical management, nearly half of affected children have subtle neurocognitive deficits. Whereas timing and type of surgical intervention have been studied, the possibility of genetic influence on neurodevelopment in nonsyndromic craniosynostosis patients remains unexplored. The authors performed whole-exome sequencing for 404 case-parent trios with sporadic nonsyndromic craniosynostosis. Statistical analyses were performed to assess the burden of de novo mutations in cases compared to both expectation and 1789 healthy control trios. Individuals with and without each mutation class were analyzed, and the presence or absence of various types of neurodevelopmental delay were recorded alongside demographic information. The authors identified a highly significant burden of damaging de novo mutations in mutation-intolerant [probability of loss of function intolerance (pLI) >0.9] genes in nonsyndromic craniosynostosis probands (p = 5.9 × 10-6). Children with these mutations had a two-fold higher incidence of neurodevelopmental delay (p = 0.001) and a more than 20-fold greater incidence of intellectual disability (p = 7.2 × 10-7), and were 3.6-fold more likely to have delays that persisted past 5 years of age (p = 4.4 × 10-4) in comparison with children with nonsyndromic craniosynostosis without these mutations. Transmitted loss of function mutations in high-pLI genes also conferred a 1.9-fold greater risk of neurodevelopmental delay (p = 4.5 ×10-4). These findings implicate genetic lesions concurrently impacting neurodevelopment and cranial morphogenesis in the pathoetiology of nonsyndromic craniosynostosis and identify a strong genetic influence on neurodevelopmental outcomes in affected children. These findings may eventually prove useful in determining which children with nonsyndromic craniosynostosis are most likely to benefit from surgical intervention. Risk, III.

Facial Dysmorphology in Saethre-Chotzen Syndrome.

Classic features of Saethre-Chotzen syndrome (SCS) described in the literature include a prominent nasal bridge, eyelid ptosis, telorbitism, maxillary hypoplasia, and mandibular prognathism. The purpose of this study was to evaluate objectively the bony features of SCS. Preoperative computer tomography scans of 15 SCS patients, 23 normal controls, 13 bicoronal nonsyndromic, and 7 unicoronal nonsyndromic craniosynostosis patients were included for analysis. Unaffected controls and nonsyndromic patients were age- and sex-matched to SCS patients. Morphometric cephalometrics were analyzed using three-dimensional computer tomography reconstructions. Mann-Whitney U were used to compare facial measurements between SCS and normal and nonsyndromic craniosynostosis controls. Telorbitism was present in bicoronal SCS patients only (P = 0.04) but absent in the unicoronal and bicoronal/metopic cohorts. The angle of the nasal bone relative to the sella was not different between SCS and controls (P = 0.536), although the angle of the nasal bone relative to the forehead was decreased in SCS by 15.5° (P < 0.001). Saethre-Chotzen syndrome had a 2.6° maxillary retrusion relative to controls (P = 0.03). In addition, SCS patients aged 4 to 7 months had a wider (39.34 versus 35.04, P = 0.017) and anteroposteriorly foreshortened (32.12 versus 35.06, P = 0.039) maxilla. There was no difference in mandibular prognathism among SCS patients as measured by the sella-nasion-B point angle compared to controls (P = 0.705). Despite classic descriptions, on morphometric analysis SCS patients did not demonstrate consistency across all suture subtypes in terms of telorbitism, a broad nasal bridge, or mandibular prognathism. Rather, SCS subtypes of SCS based on suture pathology more closely resemble nonsyndromic patients.

Ophthalmic features of craniosynostosis: A Malaysian experience.

This study aims to collect local Malaysian data regarding the ophthalmic features and complications in craniosynostosis patients who attended the Combined Craniofacial Clinic (CFC) in University Malaya Medical Centre (UMMC). Retrospective study of medical notes of craniosynostosis patients who attended the CFC in UMMC from 2014 to December 2020. Out of 37 patients, 29 had syndromic craniosynostosis, and 8 had non-syndromic craniosynostosis. Visual impairment was present in 32.1% of patients. Causes for visual impairment were as follows - amblyopia (25.0%), exposure keratopathy (3.6%), and optic atrophy (3.6%). Hypermetropia and myopia were each seen in 20.6% of patients. Astigmatism was seen in 47.1% of patients, and 29.1% had anisometropia. Proptosis was present in 78.6% and lagophthalmos in 53.3% of patients. Strabismus in primary position occurred in 51.7% of patients. Thirty-one percent of the patients had exposure keratopathy. Optic disc atrophy was seen in 13.7% of patients, and 8.3% had optic disc swelling. Optic disc swelling was resolved in all patients who underwent craniofacial surgery. Our experience in Malaysia was consistent with previously reported data on ophthalmic features of craniosynostosis patients. Additionally, we found that non-syndromic craniosynostosis patients are also at risk of ocular complications just as much as syndromic patients. Appropriate treatment of amblyogenic risk factors, ocular complications, and timely detection of papilledema, and prompt surgical intervention are crucial in preserving long-term visual function in these patients.

Neurologic Characterization of Craniosynostosis: Can Direct Brain Recordings Predict Language Development?

Nonsyndromic craniosynostosis (NSC) is associated with language deficits. Conventional tests, such as the Bayley Scales of Infant Development (BSID), may not reflect accurate long-term cognition. Alternatively, mismatch negativity (MMN) waves recorded via electroencephalogram (EEG) measure neural responses to speech and may objectively predict language development. This study aimed to (1) correlate infant MMN to future language achievement and (2) compare MMN among subtypes of NSC. Pre and postoperatively (mean operative age 9.5 months), NSC participants received the BSID and EEG phoneme-discrimination paradigm(80 dB,250 Hz). The MMN was the largest negative amplitude in the difference wave 80 to 300 ms after stimuli. To measure cognitive outcome, patients completed a neurodevelopmental battery (Wechsler-Abbreviated Scale of Intelligence and Wechsler-Fundamentals) at >6 years of age. Eleven NSC patients with EEG testing in infancy were neurocognitively tested (average age 8.0 years; 27% female; 55% sagittal, 27% metopic, 9% unicoronal, 9% sagittal/metopic). The left frontal cluster MMN strongly correlated with word-reading (r = 0.713, P = 0.031), reading-comprehension (r = 0.745, P = 0.021), and language-composites (r = 0.0771, P = 0.015). Conversely, BSID scores did not yield significant predictive value (r < 0.5, P > 0.05). Follow-up event related potentials (ERP) comparison included 39 normal control, 18 sagittal, 17 metopic, 6 unilateral-coronal infants. Preoperatively, sagittal (P = 0.003) and metopic (P = 0.003) patients had attenuated left frontal MMN compared to controls. Postoperatively, the sagittal cohort was normalized to controls while metopic patients retained attenuations (P = 0.041). ERP assessment in NSC had significantly better predictive value for future neurocognition than the BSID. Preoperatively, sagittal and metopic patients had attenuated neural response to language; postoperatively, sagittal patients had improved responses in comparison to metopic patients. Use of ERP assessment may help tailor treatment for language deficits earlier in development.

The Effect of Fronto-Orbital Advancement on Frontal Sinus Development and Function in Non-Syndromic and Syndromic Craniosynostosis.

The impact of fronto-orbital advancement (FOA) on frontal sinus development and function is anecdotally variable. The aim of this study was to assess the impact of FOA on development of frontal sinuses, and additionally to identify the complications that might arise out of such procedures. This was a retrospective case-control study. Non-syndromic and syndromic craniosynostosis patients (n = 58) who underwent FOA at an early age and also had a skull radiograph or CT scan after the age of 12 were selected. Age matched trauma patients with CT scans done beyond 12 years of age were used as controls. Age at first FOA surgery, total number of procedures and age at imaging was noted. Presence or absence of frontal sinuses was assessed using imaging studies initially. Patients with a formed frontal sinus and a CT scan were further chosen for volumetric studies. Complications related to frontal sinus and secondary surgeries were recorded. One of 27 non-syndromic patients had absent frontal sinuses. Seven of 31 syndromic patients had absent sinuses. Among 20 controls, only 1 patient did not develop frontal sinuses. The mean age at first FOA was 11.81 months and 18.25 months for non-syndromic and syndromic groups, respectively. The average number of procedures before 12 years of age was 1.25 and 1.51 for non-syndromic and syndromic patients, respectively. The mean age at imaging was 17.74, 20.96, and 20.25 years for non-syndromic, syndromic and control groups, respectively. The mean frontal sinus volumes were 13050.36, 15039.02, and 8459.48 mm for non-syndromic, syndromic and control groups, respectively. In conclusion, FOA does not seem to have an impact on rate of pneumatization in the background of similar rates in the non-syndromic and control groups. The low pneumatization rate in syndromic group might be a virtue of the disease itself. There were significant frontal sinus complications that occurred after fronto orbital advancement and this should be borne in mind during the surgical consenting process.

Management of Chiari malformation in syndromic and nonsyndromic craniosynostosis

OBJECTIVEAlthough the association between Chiari malformation (CM) and craniosynostosis is well recognized, management remains controversial. There are differences in the clinical course of CM in syndromic craniosynostosis (SC) patients and nonsyndromic craniosynostosis (NSC) patients. Still unclear is whether cranial expansion surgery, foramen magnum decompression (FMD), or both should be conducted and when the appropriate timing of surgery should be. Here, the authors retrospectively reviewed the clinical data at their institution to investigate the optimal management of CM associated with SC and NSC.METHODSThe authors retrospectively analyzed the clinical records of 163 children with craniosynostosis who underwent surgical treatment at the National Center for Child Health and Development between April 2002 and May 2018.RESULTSTwelve (10%) of 119 children with NSC and 14 (31.8%) of 44 children with SC were radiologically diagnosed with CM. The median age at which CM was radiologically diagnosed was 7 months. Of the 12 NSC patients with CM, 1 (8%) was symptomatic with gait disturbance. This patient underwent FMD following expansion surgery. Of the 14 SC patients with CM, 8 (57.1%) were symptomatic with central sleep apnea. For SC patients with symptomatic CM, cranial expansion surgery alone was conducted in 2 cases, FMD was conducted after cranial expansion in 4 cases, and FMD was conducted first and additional expansion surgery was then conducted in 2 cases. In all cases, symptoms of CM improved after completing this series of surgeries. Regarding patients with asymptomatic CM, cranial expansion surgery alone was performed, and none of the patients showed symptoms of CM thereafter in both SC and NSC cases.CONCLUSIONSMultiple surgeries tend to be necessary for symptomatic CM in both SC and NSC, while no patient with asymptomatic CM became symptomatic after cranial expansion surgery.

Frustration and Emotional Regulation in Nonsyndromic Craniosynostosis: A Functional Magnetic Resonance Imaging Study.

Nonsyndromic craniosynostosis may manifest with complex behavioral, attentional, and emotional sequelae. The authors characterized higher level brain connectivity in adolescent nonsyndromic craniosynostosis patients in response to emotional frustration. Surgically corrected patients older than 9 years with nonsyndromic craniosynostosis were age/sex/handedness matched to controls. Patients participated in a "go/no-go" task, structured as win/lose/recovery paradigms. BioImage Suite was used to analyze whole-brain intrinsic connectivity between tasks with cluster-corrected group-level t maps. A value of p < 0.05 was significant. Seven unilateral coronal (average age, 12.2 years), six metopic (average age, 11.5 years), and controls were included. Unilateral coronal had worse emotional regulation scores on the Behavior Rating Inventory of Executive Function survey (p = 0.065) and performed poorly on the go/no-go task (p < 0.001). Metopic had four regions of interest, with the majority having decreased activity compared with controls, and few differences between tasks. Unilateral coronal patients had 11 regions of interest; the majority decreased during the win and lose conditions, but all increased during the recovery condition. Metopic patients had decreased blood oxygenation level- dependent signal in the posterior cingulate (p = 0.017) and middle temporal gyrus (p = 0.042). Unilateral coronal had decreased signal in the posterior cingulate (p = 0.023), middle temporal gyrus (p = 0.027), and thalamus (p = 0.033), but increased signal in the cuneus (p = 0.009) and cerebellum (p = 0.009). Right unilateral coronal, but not metopic/controls, had increased right brain activity in the caudate (p = 0.030), thalamus (p = 0.011), temporal lobe (p = 0.012), and cerebellum (p = 0.029). Unilateral coronal patients may have emotional dysregulation in response to frustration, whereas metopic patients may have attenuated emotional reactions. Evidence of right unilateral coronal brain laterality suggests that the area of suture fusion may contribute to the mechanism of dysfunction. Risk, II.

An Investigation of Brain Functional Connectivity by Form of Craniosynostosis.

Long-term neurocognitive sequelae of nonsyndromic craniosynostosis (NSC) patients are just beginning to be clarified. This study uses functional MRI (fMRI) to determine if there is evidence of altered brain functional connectivity in NSC, and whether these aberrations vary by form of synostosis. Twenty adolescent participants with surgically treated NSC (10 sagittal synostosis, 5 right unilateral coronal synostosis [UCS], 5 metopic synostosis [MSO]) were individually matched to controls by age, gender, and handedness. A subgroup of MSO was classified as severe metopic synostosis (SMS) based on the endocranial bifrontal angle. Resting state fMRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany), and data were motion corrected and then analyzed with BioImage Suite (Yale School of Medicine). Resulting group-level t-maps were cluster corrected with nonparametric permutation tests. A region of interest analysis was performed based on the left Brodmann's Areas 7, 39, and 40. Sagittal synostosis had decreased whole-brain intrinsic connectivity compared to controls in the superior parietal lobules and the angular gyrus (P = 0.071). Unilateral coronal synostosis had decreased intrinsic connectivity throughout the prefrontal cortex (P = 0.031). The MSO cohort did not have significant findings on intrinsic connectivity, but the SMS subgroup had significantly decreased connectivity among multiple subcortical structures. Sagittal synostosis had decreased connectivity in regions associated with visuomotor integration and attention, while UCS had decreased connectivity in circuits crucial in executive function and cognition. Finally, severity of metopic synostosis may influence the degree of neurocognitive aberration. This study provides data suggestive of long-term sequelae of NSC that varies by suture type, which may underlie different phenotypes of neurocognitive impairment.

Management of craniosynostosis in Australia and New Zealand

Introduction: The management of syndromic and non-syndromic craniosynostosis is controversial with different units performing various procedures at different points in time and for different reasons. This study was performed to compare protocols of assessment and surgery in craniofacial units in Australasia.&#x0D; Methods: All paediatric craniofacial surgery centres in Australia and New Zealand were surveyed with respect to their current protocols for the preoperative assessment, intraoperative management and postoperative follow-up of syndromic and non-syndromic craniosynostosis patients.&#x0D; Results: All eight centres completed the survey with 100 per cent response rate. There was considerable homogeneity in the management of the various synostoses. Differences in management were notable in the preoperative assessments that were offered and the management of midface retrusion in syndromic craniosynostoses.&#x0D; Conclusion: Single-suture management among surveyed centres was relatively homogenous. Developmental assessment is not routinely performed for single-suture disease but is desired by the majority of surveyed centres. Postoperative CT scans are not commonly used but a number of centres desired routine use of 3D photometry for outcome assessment. In multi-suture cases, expansion of the posterior vault was performed in all cases but management of midface retrusion was variable.

Characterization of Perinatal Risk Factors and Complications Associated With Nonsyndromic Craniosynostosis.

Certain intrauterine risk factors are known to increase the risk of premature cranial suture fusion and may cause complications during birth. Some of these risk factors may be modifiable. Therefore, the authors sought to characterize the institutional patterns of prenatal risk factors and perinatal complications in nonsyndromic craniosynostosis patients compared to normal births from the surrounding area to identify areas for possible intervention or prevention. The medical records of all infants with nonsyndromic craniosynostosis and full birth records born at Duke University Health System from 2006 to 2017 were retrospectively reviewed. Maternal comorbidities, prenatal risk factors, and perinatal complications were collected. The North Carolina State Center for Health Statistics was queried for perinatal statistics from Durham county and the Northeastern Perinatal Care Region to represent a control cohort of normal births from the same time period and region. The primary outcome investigated was the incidence of prenatal risk factors and complications at birth associated with premature fusion of cranial sutures. Eighty births with nonsyndromic craniosynostosis were included in this study. The majority of these patients were males (61.7%) and born via cesarean section (55.0%). Intrauterine growth restriction occurred in 10.0% and head trauma during delivery occurred in 2.5%. Twinning (14.8% vs 3.6%, P < 0.0001), cesarean births (55.5% vs 30.0%, P < 0.0001), and breech presentation (17.3% vs 3.2%, P < 0.0001) were significantly more common in craniosynostosis patients. Prenatally, mothers of craniosynostosis infants had higher incidence of gestational diabetes (13.5% vs 5.0%, P < 0.0001) and oligohydramnios (6.1% vs 1.3%, P < 0.0001) compared to regional controls. This study demonstrates that premature suture fusion is associated with prenatal risk factors such as gestational diabetes and oligohydramnios. Continued research into potentially modifiable prenatal risk factors and more refined prenatal diagnostic tools has the potential to reduce both the incidence of premature suture fusion and the sequelae of birth complications in this population.

A Standardized Perioperative Clinical Pathway for Uncomplicated Craniosynostosis Repair Is Associated With Reduced Hospital Resource Utilization.

Hospital resource overutilization can significantly disrupt patient treatment such as cancelling surgical patients due to a lack of intensive care unit (ICU) space. The authors describe a clinical pathway (CP) designed to reduce ICU length of stay (LOS) for nonsyndromic single-suture craniosynostosis (nsSSC) patients undergoing cranial vault reconstruction (CVR) in order to minimize surgical disruptions and improve patient outcomes. A multidisciplinary team implemented a perioperative CP including scheduled laboratory testing to decrease ICU LOS. Hospital and ICU LOS, interventions, and perioperative morbidity-infection rate, cerebrospinal fluid (CSF) leaks, and unplanned return to the operating room (OR)-were compared using Mann-Whitney U, Fisher exact, and t tests. Fifty-one ICU admissions were managed with the standardized CP and compared to 49 admissions in the 12 months prior to pathway implementation. There was a significant reduction in ICU LOS (control: mean 1.84 ± 0.93, median 1.89 ± 0.94; CP: mean 1.15 ± 0.34, median 1.03 ± 0.34 days; P < 0.001 for both). There were similar rates of hypotension requiring intervention (CP: 2, control: 1; P = 0.999), postoperative transfusion (CP: 3, control: 0; P = 0.243), and artificial ventilation (CP: 1, control: 0; P = 0.999). Perioperative morbidity such as infection (CP: 1, control: 0; P = 0.999), return to the OR (CP: 1, control: 0; P = 0.999), and CSF leak (no leaks; P = 0.999) was also similar. Implementation of a standardized perioperative CP for nsSSC patients resulted in a significantly shorter ICU LOS without a measured change in perioperative morbidity. Pathways such as the one described that improve patient throughput and decrease resource utilization benefit craniofacial teams in conducting an efficient service while providing high-quality care.

Outcomes of 40 Nonsyndromic Sagittal Craniosynostosis Patients as Adults: A Case-Control Study With 26 Years of Postoperative Follow-up.

While sagittal synostosis is the most common craniosynostosis, long-term follow-up of these patients is lacking. To evaluate the results of surgical management of those patients with sagittal synostosis who attain adulthood. An outcome study of surgically treated isolated sagittal synostosis patients operated between 1977 and 1998 was conducted at the Craniofacial Center of Oulu University Hospital, Oulu, Finland with an average follow-up time of 26.5 yr. Patients' socioeconomic situation, satisfaction with their own facial appearance and attractiveness as rated by 2 independent panels was evaluated and compared to controls. The self-satisfaction with the patients' own appearance scored a mean of 75 mm on a visual analog scale of 100 mm between the patients and 76 mm with the control group. The subjective satisfaction of the patients with their own appearance failed to correlate with the rating of their appearance by the panels. The panels rated the patients' appearance to be on average 6 to 7 mm out of 100 mm visual analog scale less attractive than the controls. Data on socioeconomic situation, including marital status, housing, education, employment of the patients, and controls are presented. Isolated sagittal synostosis patients treated surgically were as happy with their facial appearance as were individuals in an age and gender-matched control group. Two independent panels found the patients' appearance to be only somewhat less attractive. Analysis of the socioeconomic situation and general health revealed that patients equaled that of controls.

Intraoperative intracranial pressure monitoring in the pediatric craniosynostosis population.

OBJECTIVEEvaluation of increased intracranial pressure (ICP) in the pediatric craniosynostosis population based solely on ophthalmological, clinical, and radiographic data is subjective, insensitive, and inconsistent. The aim of this study was to examine the intraoperative ICP before and after craniectomy in this patient population.METHODSThe authors measured the ICP before and after craniectomy using a subdural ICP monitor in 45 children. They regulated end-tidal carbon dioxide and the monitoring site under general anesthesia to record consistent ICP readings.RESULTSThe average age of the patient population was 29 months (range 3.8-180.5 months). Thirty-seven patients (82.2%) were undergoing initial craniosynostosis procedures. All craniosynostosis procedures were categorized as one of the following: frontoorbital advancement (n = 24), frontoorbital advancement with distraction osteogenesis (n = 1), posterior vault distraction osteogenesis (n = 10), and posterior vault reconstruction (n = 10). Nineteen of 45 patients (42.2%) had syndromic or multisuture craniosynostosis. The mean postcraniectomy ICP (8.8 mm Hg, range 2-18 mm Hg) was significantly lower than the precraniectomy ICP (16.5 mm Hg, range 6-35 mm Hg) (p < 0.001). Twenty-four patients (53%) had elevated ICP prior to craniectomy, defined as ≥ 15 mm Hg. Only 4 (8.9%) children had papilledema on preoperative funduscopic examination (sensitivity 17%, specificity 100%, negative predictive value 51%, and positive predictive value 100%). There were no significant differences in elevated precraniectomy ICP based on type of craniosynostosis (syndromic/multisuture or nonsyndromic) or age at the time of surgery. Patients undergoing initial surgery in the first 12 months of life were significantly less likely to have elevated precraniectomy ICP compared with patients older than 12 months (26.3% vs 73.1%, p = 0.005).CONCLUSIONSIn this study, the authors report the largest cohort of syndromic and nonsyndromic craniosynostosis patients (n = 45) who underwent precraniectomy and postcraniectomy ICP evaluation. A craniectomy or completed craniotomy cuts for distractors effectively reduced ICP in 43/45 patients. The authors' findings support the notion that papilledema on funduscopy is a highly specific, however poorly sensitive, indicator of increased ICP, and thus is not a reliable screening method. These findings indicate that even nonsyndromic patients with craniosynostosis are at risk for increased ICP. Furthermore, patients who present prior to 12 months of age appear less likely to have elevated ICP on presentation. Further studies with other noninvasive imaging of the retina may be useful as an adjunct tool for determining elevated ICP.