Nonsyndromic Sagittal Craniosynostosis Research Articles

Reassessing the association: Evaluation of a polyalanine deletion variant of RUNX2 in non-syndromic sagittal and metopic craniosynostosis.

The RUNT-related transcription factor RUNX2 plays a critical role in osteoblast differentiation, and alterations to gene dosage cause distinct craniofacial anomalies. Uniquely amongst the RUNT-related family, vertebrate RUNX2 encodes a polyglutamine/polyalanine repeat (Gln23-Glu-Ala17 in humans), with the length of the polyalanine component completely conserved in great apes. Surprisingly, a frequent 6-amino acid deletion polymorphism, p.(Ala84_Ala89)del, occurs in humans (termed 11A allele), and a previous association study (Cuellar etal. Bone 137:115395;2020) reported that the 11A variant was significantly more frequent in non-syndromic sagittal craniosynostosis (nsSag; allele frequency [AF] = 0.156; 95% confidence interval [CI] 0.126-0.189) compared to non-syndromic metopic craniosynostosis (nsMet; AF = 0.068; 95% CI 0.045-0.098). However, the gnomAD v.2.1.1 control population used by Cuellar etal. did not display Hardy-Weinberg equilibrium, hampering interpretation. To re-examine this association, we genotyped the RUNX2 11A polymorphism in 225 individuals with sporadic nsSag as parent-child trios and 164 singletons with sporadic nsMet, restricting our analysis to individuals of European ancestry. We compared observed allele frequencies to the non-transmitted alleles in the parent-child trios, and to the genome sequencing data from gnomAD v.4, which display Hardy-Weinberg equilibrium. Observed AFs (and 95% CI) were 0.076 (0.053-0.104) in nsSag and 0.082 (0.055-0.118) in nsMet, compared with 0.062 (0.042-0.089) in non-transmitted parental alleles and 0.065 (0.063-0.067) in gnomAD v.4.0.0 non-Finnish European control genomes. In summary, we observed a non-significant excess, compared to gnomAD data, of 11A alleles in both nsSag (relative risk 1.18, 95% CI 0.83-1.67) and nsMet (relative risk 1.29, 95% CI 0.87-1.92), but we did not replicate the much higher excess of RUNX2 11A alleles in nsSag previously reported (p = 0.0001).

Cognitive Outcomes of Children With Sagittal Craniosynostosis Treated With Either Endoscopic or Open Calvarial Vault Surgery

Several studies have reported a higher incidence of neurodevelopmental delays and cognitive deficits in patients with single-suture craniosynostosis; however, there are few studies examining the associations of repair type with cognitive outcomes. To measure differences in neuropsychological outcomes between school-age children who were treated for sagittal craniosynostosis and unaffected controls and explore differences in cognitive function among children with sagittal craniosynostosis who were previously treated with either endoscopic strip craniectomy or open calvarial vault surgery. This cohort study was performed between 2018 and 2022. Eligible participants included patients aged 5 to 17 years who had previously been seen as infants or toddlers (<3 years) at 1 of 3 surgical centers for craniosynostosis repair with either endoscopic surgery or open calvarial vault surgery. A separate cohort of unaffected controls were included for comparison. Data analysis was conducted from November 2023 to February 2024. Open calvarial vault surgery or endoscopic repair for single-suture craniosynostosis. The primary outcome was the Differential Ability Scales-II (DAS-II) General Conceptual Ability (GCA) score, an index for overall intellectual ability. Secondary outcomes included DAS-II subscale scores (Verbal Ability, Nonverbal Reasoning, Spatial Ability, Working Memory, and Processing Speed), and Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function scores. A total of 81 patients with sagittal craniosynostosis (59 male [73%]; 22 female [27%]) and 141 controls (81 male [57%]; 60 female [43%]) were included. Of the 81 participants with sagittal craniosynostosis, 46 underwent endoscopic repair and 35 underwent open repair. Median (range) age at time of follow-up assessment was 7.7 (5.0-14.8) years for children with sagittal craniosynostosis and median age at assessment was 8.5 (7.7-10.5) years for controls. After controlling for age at assessment, sex, and socioeconomic status, there was no statistically significant or clinically meaningful difference in GCA scores between children who underwent endoscopic repair (adjusted mean score, 100; 95% CI, 96-104) and open repair (adjusted mean score, 103; 95% CI, 98-108) (P > .99). We found no significant difference in PROMIS scores between repair types (median [range] for endoscopic repair 54 [31-68] vs median [range] for open repair 50 [32-63]; P = .14). When comparing the treatment groups with the unaffected controls, differences in subscale scores for GCA and working memory were observed but were within normal range. In this cohort study, there were no statistically or clinically significant differences in cognitive outcomes among school-age children by and type of surgical procedure used to repair nonsyndromic sagittal craniosynostosis. These findings suggest primary care clinicians should be educated about different options for craniosynostosis surgery to ensure early referral of these patients so that all treatment options remain viable.

Whole genome sequencing identifies associations for nonsyndromic sagittal craniosynostosis with the intergenic region of BMP2 and noncoding RNA gene LINC01428

Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal nonsyndromic craniosynostosis (sNCS) presenting as the most common CS phenotype. Previous genome-wide association and targeted sequencing analyses of sNCS have identified multiple associated loci, with the strongest association on chromosome 20. Herein, we report the first whole-genome sequencing study of sNCS using 63 proband-parent trios. Sequencing data for these trios were analyzed using the transmission disequilibrium test (TDT) and rare variant TDT (rvTDT) to identify high-risk rare gene variants. Sequencing data were also examined for copy number variants (CNVs) and de novo variants. TDT analysis identified a highly significant locus at 20p12.3, localized to the intergenic region between BMP2 and the noncoding RNA gene LINC01428. Three variants (rs6054763, rs6054764, rs932517) were identified as potential causal variants due to their probability of being transcription factor binding sites, deleterious combined annotation dependent depletion scores, and high minor allele enrichment in probands. Morphometric analysis of cranial vault shape in an unaffected cohort validated the effect of these three single nucleotide variants (SNVs) on dolichocephaly. No genome-wide significant rare variants, de novo loci, or CNVs were identified. Future efforts to identify risk variants for sNCS should include sequencing of larger and more diverse population samples and increased omics analyses, such as RNA-seq and ATAC-seq.

QEEG findings in nonsyndromic sagittal craniosynostosis

Despite the undertaken treatment, children with nonsyndromic sagittal craniosynostosis (NSC) are burdened with problems with speech development, visuospatial and other cognitive deficits. The electroencephalographic assessment has not influenced the diagnostics and treatment strategy of craniosynostosis so far but the introduction of quantitative EEG (QEEG) protocols renewed an interest in the functional aspect of this disease. In this study we retrospectively assessed the QEEG records of 25 children with NSC aged 1–18 months (mean age 9.62 months) before and after surgery. In each case, the amplitude, interhemispheric (ICoh) and intrahemispheric (HCoh) coherence indices were calculated. Obtained data were compared to age-matched control group of 25 normocephalic children. Children with NSC presented significantly lower values of amplitudes and intrahemispheric coherence in occipital, posterior parietal and posterior temporal regions than normocephalic children. The values of amplitudes, ICoh and HCoh in pre- and postoperative QEEG records mostly remained unchanged, with a slight improvement in HCoh in centro-parietal area. These findings suggest that NSC children present their own QEEG profile. The operative treatment improves an intrahemispheric connectivity, but there still exists a significant difference in the occipitotemporal, frontotemporal and centro-frontal areas, which may be considered as a functional substrate of reported speech and neurocognitive problems. QEEG findings in nonsyndromic sagittal craniosynostosis.

Patient-reported outcome measures more than fifteen years after treatment of sagittal or metopic craniosynostosis: a prospective cohort study

PurposeTo evaluate the long-term anthropometric measurements, cosmetic satisfaction, and other patient-reported outcome measures (PROMs) of patients who underwent surgical treatment or observation only of sagittal or metopic single-suture craniosynostosis (SSC).MethodsA prospective study was designed for all patients diagnosed with non-syndromic sagittal and metopic craniosynostosis at the British Columbia Children’s Hospital, Vancouver, Canada, in the period July 1986 to July 2006. After a minimum of 15 years post-diagnosis, all eligible patients were invited to fill out the Craniofacial Surgery Outcomes Questionnaire (CSO-Q) and to attend a scheduled follow-up appointment for the collection of anthropometric measurements. A descriptive analysis of the cosmetic results was performed. Statistical analyses compared the differences in anthropometric measurements between treated and non-treated patients.ResultsOf the 253 eligible patients, 52 participants were willing to share patient data for use in the study. Of those 52 former patients, 36 (69.2%) filled out and returned the CSO-Q and 23 (44.2%) attended the follow-up appointment. The mean follow-up period between surgical treatment and the CSO-Q was 20.2 ± 2.5 years and between surgical treatment and the follow-up appointment was 20.9 ± 2.7 years. In patients with sagittal SSC, the mean cephalic index (CI) was significantly larger in treated than in non-treated patients (74.6 versus 69.1, p = 0.04), while the mean pupillary distance and forehead to back index were significantly smaller (pupillary distance 6.0 cm versus 6.7 cm [p = 0.04] and forehead to back index 19.6 cm versus 21.1 cm [p = 0.03]). Focusing more on the patient reported outcome measures, overall cosmetic satisfaction was found to be high (80.6%) and no differences were found between sagittal and metopic synostosis patients, nor between treated or non-treated craniosynostosis patients. Overall outcomes regarding self-esteem (RSES) and fear of negative evaluation (FNE) were comparable with population based outcomes.ConclusionThis is the first prospective study of sagittal and metopic craniosynostosis patients regarding long-term anthropometric outcome and patient reported outcome measures, including patients who were treated surgically and those who received observation only. Although study participation two decades after initial diagnosis was difficult to obtain, our data provide a platform from which one can develop an inclusive and uniform approach to assess patients’ subjective cosmetic satisfaction using the CSO-Questionnaire and might be useful in preoperative counseling and psychosocial care for patients and their families.

Comparison of Fluid Replacement with Sterofundin ISO® vs. Deltajonin® in Infants Undergoing Craniofacial Surgery-A Retrospective Study.

The purpose of this study was to compare the effects of Sterofundin ISO® (SF) therapy with the balanced isochloremic solution Deltajonin® (DJ) (106 mmol/L chloride) on the acid-base status in infants undergoing craniofacial surgery. This retrospective, non-blinded study included 100 infants undergoing craniectomy due to isolated nonsyndromic sagittal craniosynostosis. The first 50 infants received Sterofundin ISO®. Due to changes in national guidelines, the infusion was changed to the isoionic Deltajonin® in an additional 50 infants in 2017. Pre- and postoperative values of chloride, pH, base excess, bicarbonate, and albumin and phosphate were determined, and the strong-ion difference, strong-ion gap, anion gap, and weak acids were calculated. Both groups were comparable in terms of their age, sex, underlying disease, preoperative electrolytes (except K at 3.9 ± 0.3 mmol/L (SF) vs. 4.1 ± 0.3 mmol/L (DJ) and lactate 8.7 ± 2.1 (SF) vs. 9.6 ± 2.6 mmol/L (DJ)). In the Sterofundin ISO® group, hyperchloremic metabolic acidosis was observed in 19 patients, whereas only 2 infants in the Deltajonin® group had hyperchloremic metabolic acidosis. The postoperative chloride level was 111 ± 2.7 mmol/L (SF) vs. 108 ± 2.4 mmol/L (DJ). The difference in anion gap was 12.5 ± 3.0 mmol/L (SF) vs. 14.6 ± 2.8 mmol/L (DJ), and the difference in SIDa (apparent strong-ion difference) was 30.9 mmol/L (SF) vs. 33.8 mmol/L (DJ). Hyperchloremic acidosis can be induced by the volume replacement with high-chloride-concentration crystalloids such as Sterofundin ISO®. This can be detected using the Stewart model.

The Accuracy of Classification Systems in Nonsyndromic Sagittal Craniosynostosis.

Numerous classification systems of nonsyndromic sagittal craniosynostosis (NSC) are applied but none has gained a wide acceptance, since each classification is focused on distinct aspects. The aim of the study was to assess the accuracy of 4 classifications of NSC discussed in the literature by defining the associations among the classifications, individual features (sex, age, cranial index), and objective morphologic criteria (frontal bossing, retrocoronal constriction, sagittal ridge, and occipital bulleting). The study was conducted on anonymized thin-cut CT scans of 133 children with NSC 1 to 12 months old (mean age 5.42mo). The type of cranial dysmorphology was assessed using 4 classification systems, focusing on skull shape, pattern of sagittal suture closure (Heuzé classification), deformation of skull vault (Sakamoto classification), and a single-dominant feature (David classification). Each patient was also independently investigated for the presence of morphologic criteria. A multivariate analysis was performed to explore the relations among the classifications and assess their accuracy. In the analyzed cohort sphenocephaly (38.3%), CFF type by Heuzé (30.8%), type I by Sakamoto (72.9%), and a central type by David (42.9%) were dominant findings. Regarding the morphologic criteria, frontal bossing was observed the most frequently (91.7%). The age of patients and cranial index differed significantly among the shapes of skull and David classifications ( P <0.001). The shape-based system showed the strongest correlation with other classifications and with measurable variables. Other classifications have much in common and some overlap, but none of them constitutes a standalone system to define all aspects of cranial dysmorphology in NSC.

Head Shape After Sagittal Craniosynostosis Surgery: Open Versus Endoscopic Strip Craniectomy

Purpose: Nonsyndromic sagittal craniosynostosis is treated surgically to improve skull cosmesis and to decrease the risk of raised intracranial pressure. The purpose of this study is to compare the outcomes of two current surgical techniques for craniosynostosis treatment, open and endoscopic strip craniectomy. Methods: A single institution retrospective chart review was conducted of patients with nonsyndromic sagittal craniosynostosis treated surgically from 2011 to 2016. Patients were divided into two groups based on surgical technique: open or endoscopic strip craniectomy. The head shape was assessed using pre- and postoperative cephalic index (CI). Complications and operative details were compared. Mean absolute CI over time and 95% confidence intervals were graphed. Results: A total of 51 children (36 male, 15 female; 13 open, 38 endoscopic) were included with an average length of follow-up of 27.2 months (range 4-60). The median age at surgery was 4.0 months for open and 3.0 months for endoscopic. There was no significant difference in preoperative CI between endoscopic and open groups (0.67 vs 0.66). The largest improvements in CI were seen 3 to 6 months postoperatively. There was a significant improvement in postoperative CI for both groups (endoscopic 0.75, P = .02; open = 0.74, P &lt; .01). From maximal postoperative CI to &gt;2 year follow up there was no significant regression in CI for the endoscopic group ( P = .12) and a small regression for the open group (−0.02, P = .01). There were no transfusions, brain injuries, or deaths. Patients in the endoscopic group had significantly less blood loss intraoperatively ( P = .01) and a significantly shorter duration of hospital stay compared to the open group ( P &lt; .001). Conclusions: Endoscopic and open surgical techniques are both effective treatments for nonsyndromic sagittal synostosis, with no difference in initial postoperative CI. These findings support the use of either technique and corroborate previous literature.

Radiomorphologic profiles of nonsyndromic sagittal craniosynostosis

PurposeNumerous classification systems of nonsyndromic sagittal craniosynostosis (NSC) are applied but none has gained a wide acceptance, since each classification is focused on distinct aspects of cranial dysmorphology. The goal of this study was to depict the most common combinations of radiomorphologic characteristics of NSC and to separate groups where the patients were morphologically similar to one another and at the same time significantly different from others.MethodsThe study was conducted on anonymized thin-cut CT scans of 131 children with NSC aged 1–12 months (mean age 5.42 months). The type of cranial dysmorphology was assessed using four criteria: skull shape, pattern of sagittal suture fusion, morphologic features and cerebrospinal fluid (CSF) spaces alterations. After assigning the categories, an unsupervised k-modes clustering algorithm was applied to identify distinct patients clusters representing radiomorphologic profiles determined by investigated characteristics.ResultsCluster analysis revealed three distinct radiomorphologic profiles including the most common combinations of features. The profiles were not influenced by sex nor age but were significantly determined by skull shape (V = 0.58, P < 0.0001), morphologic features (V = 0.50, P < 0.0001) and pattern of sagittal suture fusion (V = 0.47, P < 0.0001). CSF alterations did not significantly correlate with the profiles (P = 0.3585).ConclusionNSC is a mosaic of radiologic and morphologic features. The internal diversity of NSC results in dissimilar groups of patients defined by unique combinations of radiomorphologic characteristics, from which the skull shape is the most differentiating factor. Radiomorphologic profiles support the idea of clinical trials targeted at more selective outcomes assessment.

Correlation between degree of sagittal suture fusion and surrogates of elevated intracranial pressure in sagittal craniosynostosis.

Sagittal craniosynostosis constricts transverse skull growth, with possible neurocognitive sequelae. While the degree of sagittal suture fusion has been shown to influence the degree of dysmorphology, it is unknown if it impacts functional findings, including elevated intracranial pressure (ICP). The purpose of this study was to determine associations between the degree of sagittal suture fusion and optical coherence tomography (OCT) surrogates suggestive of increased ICP in patients with nonsyndromic sagittal craniosynostosis. Three-dimensional CT head images of patients with sagittal craniosynostosis were analyzed in Materialise Mimics and parietal bones were manually isolated to determine the percentage fusion of the sagittal suture. Retinal OCT was performed prior to the cranial vault procedure with analysis for thresholds that correlate with elevated ICP. The degree of sagittal suture fusion was compared with OCT retinal parameter measurements using Mann-Whitney U-tests, Spearman's correlations, and multivariate logistic regression models controlled for age. Forty patients (31 males) with nonsyndromic sagittal craniosynostosis at a mean (± SD) age of 3.4 ± 0.4 months were included in this study. OCT surrogates of elevated ICP (maximal retinal nerve fiber layer [RNFL] thickness and maximal anterior projection [MAP]) were not associated with total sagittal suture fusion (p > 0.05). Maximal RNFL thickness was positively associated with increased percentage of posterior one-half (rho = 0.410, p = 0.022) and posterior one-third (rho = 0.417, p = 0.020) sagittal suture fusion. MAP was also positively associated with increased percentage of posterior one-half (rho = 0.596, p < 0.001) and posterior one-third (rho = 0.599, p < 0.001) sagittal suture fusion. Multivariate logistic regression models revealed increased percentage of posterior one-half (p = 0.048) and posterior one-third (p = 0.039) sagittal suture fusion predicted ICP > 20 mm Hg. Increased percentage fusion of the posterior sagittal suture, but not total suture, was positively associated with retinal changes indicative of increased ICP. These findings suggest suture fusion leading to increased ICP may be region specific.

306 Long-Term Appearance and Outcomes after Strip Craniectomy Compared with Open Cranial Vault Reconstruction for Sagittal Craniosynostosis

OBJECTIVES/GOALS: Strip craniectomy with orthotic helmet therapy (SCOT) and open cranial vault reconstruction (OCVR) are mainstay surgical treatments for sagittal craniosynostosis. The purpose of this study is to compare long-term morphologic outcomes of the skull, subjective appearance, and perioperative outcomes between patients who underwent SCOT and OCVR. METHODS/STUDY POPULATION: Patients who underwent SCOT or OCVR for isolated, non-syndromic sagittal craniosynostosis with preoperative computerized tomography (CT) imaging were identified at UCSF between 2000 and 2020. Perioperative outcomes were extracted from the medical chart. Anthropometric measurements will be used to assess baseline severity using preoperative CT imaging and postoperative skull morphology using 3D camera imaging. Patient satisfaction surveys will be administered to parents at the time of postoperative 3D imaging. Subjective appearance will be rated among adolescents and craniofacial surgeons using patients’ postoperative 3D imaging. Descriptive statistics will be calculated using Student’s t test and Mann-Whitney U. Chi-square tests and Fisher exact tests will be used to compare categorical outcomes. RESULTS/ANTICIPATED RESULTS: 47 patients were included in the study (18 SCOT and 29 OCVR) with similar follow-up between groups (SCOT 2.3 +/- 1.5, OCVR 2.6 +/- 2.0). There were no significant differences in sex or race. OCVR had longer operative times (p-value 0.0003), higher estimated blood loss (p DISCUSSION/SIGNIFICANCE: SCOT was associated with superior perioperative outcomes compared with OCVR due to its minimally invasive technique. Our results for long-term healing outcomes and subjective appearance may further guide craniofacial surgeons in selecting the most optimal operative technique.

Early bone reformation after cranial vault remodelling for sagittal craniosynostosis: A retrospective 3D analysis

This study aims to measure postoperative bone reformation percentage, rates and patterns after cranial vault remodelling (CVR) in isolated non-syndromic sagittal craniosynostosis. Volumetric bone measurements were performed starting from the DICOM files of previously available postoperative CT scans. The 3D images were then resampled into the master box, and ‘Skull 3D models’ were derived. The percentage of bone reformation was investigated using automated 3D analysis software. The intra-rater reliability analysis revealed high reliability (Intraclass correlation coefficient = 0.99, p < 0.001). The median bone reformation volume and rate were 11.2 ml and 1.98 ml/week, respectively. The median percentage of bone reformation was 56.7% when the median postoperative CT timing was 6.1 weeks. As a statistic model, the linear plateau showed the highest Pseudo R2 in both volume and percentage of bone reformation predicting patterns. By using the calculated model at 9 weeks postoperatively, the re-osteogenesis reaches 80% of the total cranial defect. After CVR, the early bone reformation pattern was demonstrated as a linear plateau model rather than logarithmic. This study gives a better understanding of the pattern and quantity of re-osteogenesis at cranial defects after CVR. The statistic model can facilitate healthcare practitioners to predict bone reformation and improve postoperative care protocol in sagittal craniosynostosis management.

Quantifying the Impact of Genetics on Neurocognition in Non-Syndromic Sagittal Craniosynostosis.

Previous work has identified an association between de novo and transmitted loss of function mutations in genes under high evolutionary constraint (high pLI) with neurodevelopmental delays in non-syndromic craniosynostosis (NSC). We sought to quantify the neurocognitive effect of these genetic lesions. In a prospective, double-blinded cohort study, demographic surveys and neurocognitive tests were administered to patients recruited from a national sample of children with sagittal NSC. Scores for academic achievement, full-scale intelligence quotient (FSIQ), and visuomotor skills were directly compared between patients with and without damaging mutations in high pLI genes using two-tailed t tests. Analysis of covariance was also used to compare test scores while controlling for surgery type, age at surgery, and sociodemographic risk. 56 patients completed neurocognitive testing, 18 of whom had a mutation in a highly constrained gene. There was no significant difference between groups in any sociodemographic factors. After controlling for patient factors, patients with high-risk mutations had poorer performance compared to patients without high-risk mutations in every testing category, with significant differences in FSIQ (102.9 ± 11.4 vs. 110.1 ± 11.3, P=0.033) and visuomotor integration (100.0 ± 11.9 vs. 105.2 ± 9.5, P=0.003). There were no significant differences in neurocognitive outcome when stratifying groups based on type of surgery or age at time of surgery. Even after controlling for exogenous factors, the presence of mutations in high-risk genes led to poorer neurocognitive outcomes. High risk genotypes may predispose individuals with NSC to deficits, particularly in full-scale IQ and visuomotor integration.

Intracranial hypertension complicated with blindness in a child with non-syndromic sagittal craniosynostosis: a case report

Intracranial hypertension complicated with blindness in a child with non-syndromic sagittal craniosynostosis: a case report

The current understanding of germline predisposition in non-syndromic sagittal craniosynostosis: a systematic review.

The objective of this literature review was to provide a comprehensive and up-to-date overview of the current understanding of the genetic etiology for non-syndromic sagittal craniosynostosis. Using the PubMed database and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we systematically reviewed relevant records on germline genetics in children with non-syndromic sagittal craniosynostosis. Two hundred two records were identified, of which 25 were included following title and abstract screening and subsequent full-text review. The 25 records in combination included 829 children with non-syndromic sagittal craniosynostosis. A likely pathogenic or pathogenic germline variant was reported for 9.8% of the 827 patients for whom germline genetic testing was performed. The reported variants were distributed across 50 different genes, with more than one variant detected in 13 genes. Based on the existing literature, genetic predisposition is likely to play a role in at least 9% of children with non-syndromic sagittal craniosynostosis. Future studies will benefit from international consensus in terms of diagnostic nomenclature and a higher level of standardization across study methodologies and bioinformatic approaches.

Spring forces and calvarial thickness predict cephalic index changes following spring-mediated cranioplasty for sagittal craniosynostosis.

Variables interacting to predict outcomes following spring-mediated cranioplasty (SMC) for non-syndromic craniosynostosis, including spring parameters and calvarial thickness, are poorly understood. This study assessed interactions between spring parameters and calvarial thickness to predict changes in cephalic index (CI) following SMC. Patients undergoing SMC for non-syndromic sagittal craniosynostosis at our institution between 2014 and 2021 were included. Calvarial thickness was determined from patient preoperative CTs using Materalise Mimics at 27 points in relation to the sagittal suture. Linear mixed effects models were used to determine interactions between anterior, middle, and posterior calvarial thickness with spring force and length. Sixty-nine patients undergoing surgery at mean age 3.7months were included in this study. Stronger posterior spring force interacted with thinner posterior calvarial thickness to predict greater changes in CI at 3months postoperatively (p = 0.022). When evaluating spring force and calvarial thickness set distances from the sagittal suture, stronger posterior spring force interacted with thinner posterior calvarial thickness 5mm (p = 0.043) and 10mm (p = 0.036) from the sagittal suture to predict changes in CI. Interactions between spring parameters and calvarial thickness in the anterior and middle positions did not significantly predict changes in CI. Stronger posterior spring force interacted with thinner posterior calvaria to predict greater changes in CI 3months following SMC for non-syndromic sagittal craniosynostosis. These results suggest dynamic interactions between several variables may impact outcomes following SMC.

A multi-institutional survey on calvarial vault remodeling techniques for sagittal synostosis and outcomes analysis for patients treated at 12 months and older.

Surgical treatment of sagittal craniosynostosis is challenging in older patients. This study aimed to assess the effect of increasing age on open surgical technique selection and patient outcomes using the multi-institutional Synostosis Research Group (SynRG) collaboration. Surgeons in SynRG were surveyed for key influences on their preferred open calvarial vault remodeling techniques at various patient ages: < 6, 6-12, and > 12 months. The SynRG database was then queried for open repairs of nonsyndromic sagittal craniosynostosis performed for patients older than 12 months of age. Perioperative measures, complications, and preoperative and postoperative cephalic indices were reviewed. All surgeons preferred to treat patients at an earlier age, and most (89%) believed that less-optimal outcomes were achieved at ages older than 12 months. The modified pi procedure was the dominant technique in those younger than 12 months, while more involved open surgical techniques were performed for older patients, with a wide variety of open calvarial vault remodeling techniques used. Forty-four patients met inclusion criteria, with a mean (± SD) age at surgery of 29 ± 16 months. Eleven patients underwent parietal reshaping, 10 parietal-occipital switch, 9 clamshell craniotomy, 7 geometric parietal expansion, 6 modified pi procedure, and 1 parietal distraction. There were no readmissions, complications, or mortality within 30 days postoperatively. Patients' cephalic indices improved a mean of 6.4% ± 4.0%, with a mean postoperative cephalic index of 74.2% ± 4.9%. Differences in postoperative cephalic index (p < 0.04) and hospital length of stay (p = 0.01) were significant between technique cohorts. Post hoc Tukey-Kramer analysis identified the parietal reshaping technique as being significantly associated with a reduced hospital length of stay. Patient age is an important driver in technique selection, with surgeons selecting a more involved calvarial vault remodeling technique in older children. A variety of surgical techniques were analyzed, with the parietal reshaping technique being significantly associated with reduced length of stay; however, multiple perioperative factors may be contributory and require further analysis. When performed at high-volume centers by experienced pediatric neurosurgeons and craniofacial surgeons, open calvarial vault techniques can be a safe method for treating sagittal craniosynostosis in older children.

Suture Fusion, Cephalic Index, and Head Shape in Non-syndromic Sagittal Craniosynostosis

INTRODUCTION: Sagittal craniosynostosis may present with complete or partial fusion of the sagittal suture.1 Previous studies describe high heterogeneity of phenotypic presentation for non-syndromic sagittal craniosynostosis in absence of particularly compelling evidence explaining such heterogeneity.1 One postulation for variation in head shape at presentation is degree and location of suture fusion; however, relationships between extent of sagittal suture fusion and head shape are currently poorly described.1 The aim of this study was to characterize the degree of sagittal suture fusion in a cohort of patients with non-syndromic sagittal craniosynostosis and determine associations with CI and head shape, including frontal bossing and occipital bulleting. METHODS: Patients with non-syndromic sagittal craniosynostosis at a tertiary care center with available CT imaging between 2014 and 2021 were retrospectively included in this study. Three-dimensional CT head images were imported into Materialise Mimics and parietal bones were manually isolated. The ‘measure’ tool was used to measure the distance of fused suture. The percentage of total sagittal suture fusion was quantified by dividing the distance of fused suture by the total length of the sagittal suture. Similar calculations were performed for anterior and posterior halves, and anterior, middle, and posterior thirds. Degree of sagittal suture fusion was compared to head shape characteristics, including cephalic index (CI), frontal bossing, and occipital bulleting, with Mann-Whitney U tests, Spearman’s correlations, and univariate and multivariate linear and logistic regression models. RESULTS: Ninety patients (69 male) were included in this retrospective study. The sagittal suture was on average 85.6 ± 20.1% fused, and 45 (50.0%) patients demonstrated complete fusion of the sagittal suture. CI was associated with increased degree of fusion for the anterior one-half (ρ = 0.26, p = 0.033) and anterior one-third (ρ = 0.30, p = 0.012) of the sagittal suture. Complete fusion of the anterior one-third of the sagittal suture predicted higher CI (β = 13.86, SE = 6.99, z = -0.25, p = 0.047). Logistic regression models revealed percentage of middle one-third sagittal suture fusion predicted the presence of frontal bossing (β = 2.42, SE = 0.96, z = 2.53, p = 0.012). Total degree of sagittal suture fusion was not predictive of CI or head shape in any analysis (all p > 0.05). CONCLUSION: Percentage of total sagittal suture fusion was not associated with CI or head shape in patients with non-syndromic sagittal craniosynostosis in this cohort. Decreased fusion of the anterior one-third of the sagittal suture was paradoxically associated with higher CI and more severe scaphocephalic head shape. These findings raise additional questions regarding suture fusion and head-shape morphology, and further research is needed to substantiate these results in patients with non-syndromic sagittal craniosynostosis. These findings may have implications for understanding suture fusion patterns in other variations of craniosynostosis. REFERENCE: 1. Di Rocco, F., Gleizal, A., Szathmari, A., Beuriat, P. A., Paulus, C., & Mottolese, C. (2019). Sagittal suture craniosynostosis or craniosynostoses? The heterogeneity of the most common premature fusion of the cranial sutures. Neurochirurgie, 65(5), 232-238.

Springs Forces and Parietal Bone Thickness Interact to Predict Changes in Cephalic Index following Spring-Mediated Cranioplasty for Non-Syndromic Sagittal Craniosynostosis

Springs Forces and Parietal Bone Thickness Interact to Predict Changes in Cephalic Index following Spring-Mediated Cranioplasty for Non-Syndromic Sagittal Craniosynostosis

Endoscopic strip craniectomy with molding helmet therapy versus spring-assisted cranioplasty for nonsyndromic single-suture sagittal craniosynostosis: a systematic review.

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. 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. 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. 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.