Nonsyndromic Sagittal Craniosynostosis Research Articles

The Role of Helmet Therapy in Craniosynostosis: A Systematic Review

AbstractThe aim of this study was to determine the impact of helmet therapy (HT) as a treatment for craniosynostosis, with a focus on the outcomes of skull morphology, reoperation rate, complications of HT, and quality of life of patients who receive it. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review utilized the PICO format: Does HT following strip craniectomy (SC) improve outcomes (outcome) compared to SC alone (comparison) in patients undergoing craniosynostosis correction (intervention)? Searches were performed from January 1, 2000 to December 31, 2022, using PubMed, Cochrane Library, and Ovid Medline databases. Study quality was evaluated using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment scale. Fourteen studies meeting the inclusion criteria were identified. Among these, 438 patients underwent SC-HT, while 104 patients underwent SC without HT. The preoperative cephalic indices for sagittal craniosynostosis in the HT and non-HT groups were 66.8 and 67.8, respectively, which improved postoperatively to 75 and 76.2, respectively. Limited long-term follow-up hindered a definitive assessment of reoperation rates. Complication rates related to HT were low at approximately 2.9%, primarily consisting of skin irritation. Parental satisfaction was high, correlating with a strong compliance rate. Existing literature does not demonstrate a clear superiority between SC with or without HT for treating nonsyndromic sagittal craniosynostosis. Outcomes appear comparable, but evidence is constrained by the predominance of single-center retrospective studies with limited methodological rigor. There is a pressing need for international multicenter trials to furnish more robust and generalizable findings.

The validation of morphometric outcomes and stratification system for nonsyndromic sagittal craniosynostosis following total calvarial remodeling

This study aimed to provide an external validation of morphometric outcomes, including recently developed parameters — vertico-longitudinal index (VLI) and vertex-nasion-opisthocranion (VNO) angle — along with a proposed stratification system for nonsyndromic sagittal craniosynostosis (NSC). Thin-cut CT scans performed before and after total calvarial remodeling in 70 NSC children (mean preoperative age, 7.0 months; mean postoperative age 23.8 months) were evaluated. The parameters, including linear dimensions, morphometry-based indices, and cranial angles, were measured at the cranial vault and base. Each patient was also assigned a scaphocephaly severity score (SSS). The obtained data were compared with an age-matched control group of 80 normocephalic children.After surgery, all dimensions of the cranial vault increased, but did not normalize (p < 0.0001). Contrarily, some normalization was noted in the skull base, within the anterior and posterior cranial fossae. Postoperative results confirmed the diagnostic cut-off level for VNO at 50°; however, the proposed VLI cut-offs skewed the accuracy of SSS in the control group.To the best of our knowledge, this study was the first to discuss the value of an NSC stratification system in relation to underlying components. The SSS has a relevant background, but its accuracy would increase with a redefinition of normative VLI ranges.

Early Bone and Suture Reformations in Different Cranial Regions After Cranial Vault Remodeling for Sagittal Craniosynostosis.

Cranial vault remodeling (CVR) is a common procedure for correcting sagittal craniosynostosis. Some approaches leave significant craniectomy defects. The authors investigated the reosteogenesis in different cranial defect areas after CVR. A cross-sectional study was conducted in nonsyndromic sagittal craniosynostosis. Available early postoperative computed tomography (CT) scans were analyzed. The segmentation of three-dimensional reconstructed images was performed. Different cranial defect areas, including coronal, vertex, and occipital regions, were further investigated using an automated three-dimensional analysis software for reosteogenesis percentage. Forty-four CT scans were included. The average age at CVR was 8.8 months. The median time of postoperative CT scans was 6.1 weeks. The median bone reformation percentage of the entire cranial defect was 56.7%. Given the similar postoperative CT timing, the median bone reformation at the coronal, vertex, and occipital areas demonstrated 44.21%, 41.13%, and 77.75%, respectively (P < 0.001). In the simultaneously removed coronal and lambdoid sutures, there were 45% with coronal and lambdoid sutures reformation, followed by lambdoid suture reformation alone, no suture reformation and coronal reformation alone in 35%, 20%, and 0%, respectively (P = 0.013). There was no coronal reformation in the removed coronal suture group. However, 40% demonstrated lambdoid suture reformation after the isolated lambdoid suture removal. The occipital region has the highest reosteogenesis compared with the other cranial defects after CVR in nonsyndromic sagittal craniosynostosis. Within the removed previous patent sutures, the lambdoid suture reformation showed a higher rate than the coronal suture.

A coddling of the sagittal suture: inequality in spring-assisted expansion.

We examined differences in long-term morphometric outcomes of spring-mediated cranioplasty (SMC) for various forms of isolated nonsyndromic sagittal craniosynostosis. A retrospective review was performed of children who underwent SMC from 2011 to 2020 at the Children's Hospital of Philadelphia. Cephalic indices (CI), Whitaker grades, parietal bone thickness, and degree of suture fusion were assessed. Frontal bossing and vertex-nasion-opisthocranion (VNO) angles were compared to a normal control group. Fifty-four subjects underwent surgery at age 3.6 ± 1.0 months with follow-up of 6.3 ± 1.8 years. Mean CI was 75.2 ± 4.1 at 5.9 ± 2.0 years postoperatively. Mean CI were 75.8 ± 4.1 (n = 32), 76.4 ± 4.0 (n = 22), and 77.1 ± 4.8 (n = 11) at 5, 7, and 9+ years postoperatively, respectively. Three (5.6%) required reoperation for persistent scaphocephalic cranial deformity. Fifty-one (94.4%) were Whitaker Grade I. On physical examination, 12 (22.2%) demonstrated craniofacial abnormalities. At long-term follow-up, there were no differences in frontal bossing angle (102.7 ± 5.2 degrees versus 100.7 ± 5.6 degrees, p = .052) and VNO angle (44.9 ± 3.3 degrees versus 43.9 ± 2.2 degrees, p = .063) between study and control groups. Younger age at surgery predicted a lower Whitaker grade, more normalized VNO angle, and greater change in CI during active expansion. Increased percentage fused of the posterior sagittal suture predicted a higher Whitaker grade, while decreased anterior fusion was associated with frontal bossing and temporal hollowing. Overall, children undergoing spring-mediated cranioplasty for sagittal craniosynostosis demonstrated maintenance of CI, favorable cosmetic outcomes, and a low reoperation rate at mid-term follow-up. Early intervention is associated with improved aesthetic outcomes, and regional fusion patterns may influence long-term craniofacial dysmorphology.

Cranial bone thickness and density anomalies quantified from CT images can identify chronic increased intracranial pressure

PurposeThe diagnosis of chronic increased intracranial pressure (IIP)is often based on subjective evaluation or clinical metrics with low predictive value. We aimed to quantify cranial bone changes associated with pediatric IIP using CT images and to identify patients at risk.MethodsWe retrospectively quantified local cranial bone thickness and mineral density from the CT images of children with chronic IIP and compared their statistical differences to normative children without IIP adjusting for age, sex and image resolution. Subsequently, we developed a classifier to identify IIP based on these measurements. Finally, we demonstrated our methods to explore signs of IIP in patients with non-syndromic sagittal craniosynostosis (NSSC).ResultsWe quantified a significant decrease of bone density in 48 patients with IIP compared to 1,018 normative subjects (P < .001), but no differences in bone thickness (P = .56 and P = .89 for age groups 0–2 and 2–10 years, respectively). Our classifier demonstrated 83.33% (95% CI: 69.24%, 92.03%) sensitivity and 87.13% (95% CI: 84.88%, 89.10%) specificity in identifying patients with IIP. Compared to normative subjects, 242 patients with NSSC presented significantly lower cranial bone density (P < .001), but no differences were found compared to patients with IIP (P = .57). Of patients with NSSC, 36.78% (95% CI: 30.76%, 43.22%) presented signs of IIP.ConclusionCranial bone changes associated with pediatric IIP can be quantified from CT images to support earlier diagnoses of IIP, and to study the presence of IIP secondary to cranial pathology such as non-syndromic sagittal craniosynostosis.

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.