Craniosynostosis Research Articles

Convolutional neural network-based classification of craniosynostosis and suture lines from multi-view cranial X-rays

Early and precise diagnosis of craniosynostosis (CSO), which involves premature fusion of cranial sutures in infants, is crucial for effective treatment. Although computed topography offers detailed imaging, its high radiation poses risks, especially to children. Therefore, we propose a deep-learning model for CSO and suture-line classification using 2D cranial X-rays that minimises radiation-exposure risks and offers reliable diagnoses. We used data comprising 1,047 normal and 277 CSO cases from 2006 to 2023. Our approach integrates X-ray-marker removal, head-pose standardisation, skull-cropping, and fine-tuning modules for CSO and suture-line classification using convolution neural networks (CNNs). It enhances the diagnostic accuracy and efficiency of identifying CSO from X-ray images, offering a promising alternative to traditional methods. Four CNN backbones exhibited robust performance, with F1-scores exceeding 0.96 and sensitivity and specificity exceeding 0.9, proving the potential for clinical applications. Additionally, preprocessing strategies further enhanced the accuracy, demonstrating the highest F1-scores, precision, and specificity. A qualitative analysis using gradient-weighted class activation mapping illustrated the focal points of the models. Furthermore, the suture-line classification model distinguishes five suture lines with an accuracy of > 0.9. Thus, the proposed approach can significantly reduce the time and labour required for CSO diagnosis, streamlining its management in clinical settings.

Postoperative Orbital Morphology Observations Following Fronto-Orbital Advancement and Cranial Vault Remodeling in Patients With Unilateral Coronal Synostosis.

Observations of preoperative and postoperative orbital morphology following fronto-orbital advancement and cranial vault remodeling (FOA and CVR) in patients with unilateral coronal synostosis (UCS). This retrospective cohort included patients diagnosed with unilateral coronal synostosis and treated with fronto-orbital advancement and cranial vault remodeling at the Children's Hospital of Fudan University. The orbital height, orbital width, and orbital volume were obtained from head 3-dimensional computed tomography of preoperation and postoperation. The DICOM data of CT were then imported into mimics research version 21.0. The authors measured OH and OW according to the bony landmarks, then reset the parameters of the soft tissue window, and conducted a 3-dimensional reconstruction of the orbital soft tissue to get OV. The preoperative and postoperative measurements of the intact side were compared with the affected side, respectively. Statistical analysis was performed using SPSS version 25.0 (Ρ=0.05). Twelve patients with UCS (5 male, 7 female) meeting criteria were included in the study. There were 4 patients with UCS on the left and 8 on the right. The average age at initial surgery was 19.50 months. Before the operation, the data of the intact side and the affected side were compared, respectively, and the difference was found to be significant in OH (Ρ=0.005) and OW (Ρ=0.005), while the OV (Ρ=0.106) was not statistically significant. After procedures of FOA and CVR, the data of the intact side and the affected side were compared, respectively, the significant difference was found in OV (Ρ=0.002), while not in OH (Ρ=0.060) or OW (Ρ=0.066). After undergoing the operation of FOA and CVR, the OH and OW of the ipsilateral and contralateral sides of patients with UCS were basically symmetrical, while the volume of the affected orbit was still relatively smaller.

Neuroimaging in Nonsyndromic Craniosynostosis: Key Concepts to Unlock Innovation.

Craniosynostoses (CRS) are caused by the premature fusion of one or more cranial sutures, with isolated nonsyndromic CRS accounting for most of the clinical manifestations. Such premature suture fusion impacts both skull and brain morphology and involves regions far beyond the immediate area of fusion. The combined use of different neuroimaging tools allows for an accurate depiction of the most prominent clinical-radiological features in nonsyndromic CRS but can also contribute to a deeper investigation of more subtle alterations in the underlying nervous tissue organization that may impact normal brain development. This review paper aims to provide a comprehensive framework for a better understanding of the present and future potential applications of neuroimaging techniques for evaluating nonsyndromic CRS, highlighting strategies for optimizing their use in clinical practice and offering an overview of the most relevant technological advancements in terms of diagnostic performance, radiation exposure, and cost-effectiveness.

Long-Term Outcomes of Nonsyndromic Isolated Unilateral Lambdoid Craniosynostosis

This study combined qualitative and quantitative approaches to evaluate outcomes of isolated nonsyndromic unilateral lambdoid synostosis at the Children's Hospital of Philadelphia. Volumetric, linear, and angular analyses were performed on long-term postoperative and normal control scans. Preoperative and postoperative clinical photographs were evaluated for the presence of dysmorphic frontofacial features. Among 26 included patients, median age of surgery was 10 months and mean postoperative follow-up was 5.9±5.7 years. Two (7.7%) patients underwent secondary cranial vault procedures. At most recent follow-up, 2 (7.7%) subjects reported intermittent headaches. Twenty (90.9%) of 22 patients were assigned Whitaker grade I. Among 9 subjects with long-term imaging at age 11.5±5.3, posterior vault asymmetry, posterior fossa deflection angle, cranial base angle, and ear position asymmetry all remained greater than in the control group. Of subjects included in the frontofacial feature analysis (n=10), 50% had resolution of all dysmorphic frontofacial features present preoperatively. Overall, most subjects who underwent PVR did not require revisional surgery and had good outcomes both aesthetically and functionally. Despite residual abnormalities in the cranial base and posterior vault, most had resolution of parietal bossing and facial scoliosis. Ear position asymmetry was the most common dysmorphic feature at long-term follow-up.

Biobank for craniosynostosis and faciocraniosynostosis, rare pediatric congenital craniofacial disorders: a study protocol.

Craniosynostosis (CRS) is a rare congenital cranial malformation in which 1 or more cranial or facial sutures are fused in utero or rapidly fused in early infancy. The cranial sutures separate the skull bone plates and enable rapid growth of the skull in the first 2years of life, in which growth is largely dictated by growth of the brain. CRS is a rare disease that occurs in 1 in 2100 to 1 in 2500 births and may be either nonsyndromic (also referred to as isolated) or syndromic. In syndromic CRS, other birth defects are present next to the CRS. The distinction between nonsyndromic and syndromic manifestations is made on the basis of dysmorphologic evaluation and genetic evaluation. Owing to advances in genetic diagnostics, nonsyndromic patients are increasingly recognized as syndromic patients. CRS treatment is almost entirely surgical and is sometimes paired with postoperative helmet therapy for maintenance. Corrective procedures are complex, long, and associated with the risk of numerous complications, including heavy blood loss and its sequelae. Although surgery may restore a normal appearance, even in nonsyndromic patients, patients may experience persistent deficits in intellectual ability and cognitive function. The European Commission (EC) has prioritized rare diseases in recent horizon European research programs; indeed, collections or even individual samples may be extremely valuable for research. Here, we present a study protocol in which the combined expertise of clinicians and researchers will be exploited to generate a biobank dedicated to CRS. The generation of the CRS biobank presented in this study will include the collection of different types of biological materials as well as advanced radiological images available to the scientific community. The activation of a CRS biobank will provide an opportunity to improve translational research on CRS and to share its benefits with the scientific community and patients and their families.

Paleopathological Analysis of Craniosynostosis (CS): Two Cases of Plagiocephaly from the Archaeological Site of Kayalıpınar, Sivas, Turkey

Paleopathological Analysis of Craniosynostosis (CS): Two Cases of Plagiocephaly from the Archaeological Site of Kayalıpınar, Sivas, Turkey

Epidemiologic Assessment of Craniosynostosis in Mississippi's Pediatric Population from 2015 to 2020.

This study aimed to report geographic and demographic patterns of patients with craniosynostosis (CS) treated at Children's of Mississippi, the state's only American Cleft Palate-Craniofacial Association-approved craniofacial team. Patients with CS were treated at a tertiary pediatric hospital cared for by craniofacial surgeons and neurosurgeons from 2015 to 2020. Demographic, geographic, and CS diagnosis details, including sex, gestational age, race, ethnicity, insurance status, and affected cranial suture type(s), number, and associated syndromic diagnosis were collected, including birth county and total live births from state data. Significant differences between prevalence of CS in four regions of Mississippi were examined using two-tailed t tests (P < 0.05). Among 222,819 live births in Mississippi between 2015 and 2020, 79 pediatric patients presented to Children's of Mississippi with CS, with an overall incidence of 0.355/1000 live births. Most cases were nonsyndromic CS (82%, n = 65) affecting a single major cranial suture (81%, n = 64). The overall incidence of CS was higher in the coastal and central regions compared with northeast Mississippi, at 0.333 and 0.527 vs 0.132/1000 live births (P = 0.012 and P = 0.004), respectively. Results from this study suggest regional patterns of CS in Mississippi, which may reflect actual incidence patterns or proximity to Children's of Mississippi. Further study could reveal regional differences in risk factors underlying CS incidence or access to specialized CS care for different regions in the state. This will lead to opportunities for institutional outreach to decrease the burden of CS care in Mississippi.

Vaulting further: cranial vault expansion for craniocerebral disproportion without primary craniosynostosis.

Treatment of subjects with refractory idiopathic intracranial hypertension (IIH) or shunted hydrocephalus with chronic shunt complications is challenging. What is the role for cranial vault expansion, particularly utilizing posterior vault distraction osteogenesis (PVDO), in these cases? This study assesses medium-term efficacy of cranial vault expansion in this unique patient population. A retrospective review was conducted of patients who underwent cranial vault expansion from 2008 to 2023 at the Children's Hospital of Philadelphia. Subjects who did not have a diagnosis of primary craniosynostosis were included in the study. Demographic information, medical history, and perioperative details were collected from medical records. Primary outcomes were the rate of CSF diversion procedures and resolution of presenting signs and symptoms. Secondary outcomes were perioperative and 90-day complications and reoperation requirement. Among 13 included subjects, nine (69.2%) patients had a primary diagnosis of shunted hydrocephalus and 4 (30.8%) patients had IIH. Twelve (92.3%) subjects underwent posterior vault distraction osteogenesis (PVDO) and one (7.7%) underwent posterior vault remodeling (PVR). All 4 patients with IIH demonstrated symptomatic improvement following PVDO, including resolution of headaches, vomiting, and/or papilledema. Among 9 patients with shunted hydrocephalus, CSF diversion requirement decreased from 2.7 ± 1.6 procedures per year preoperatively to 1.2 ± 1.8 per year following cranial vault expansion (p = 0.030). The mean postoperative follow-up was 4.1 ± 2.1years and four (30.8%) patients experienced complications within 90days of surgery, including infection (n = 2), CSF leak (n = 1), and elevated ICP requiring lumbar puncture (n = 1). Four (30.8%) patients underwent repeat cranial vault expansion for recurrence of ICP-related symptoms. At most recent follow-up, 7 of 9 patients with shunted hydrocephalus demonstrated symptomatic improvement. Cranial vault expansion reduced intracranial hypertension-related symptomology as well as the rate of CSF diversion-related procedures in patients with refractory IIH and shunted hydrocephalus without craniosynostosis, and should be considered in those who have significant shunt morbidity.

AXIN1 mutations in nonsyndromic craniosynostosis.

Occurring once in every 2000 live births, craniosynostosis (CS) is the most frequent cranial birth defect. Although the genetic etiologies of syndromic CS cases are well defined, the genetic cause of most nonsyndromic cases remains unknown. The authors analyzed exome or RNA sequencing data from 876 children with nonsyndromic CS, including 291 case-parent trios and 585 additional probands. The authors also utilized the GeneMatcher platform and the Gabriella Miller Kids First genome sequencing project to identify additional CS patients with AXIN1 mutations. The authors describe 11 patients with nonsyndromic CS harboring rare, damaging mutations in AXIN1, an inhibitor of Wnt signaling. AXIN1 regulates signaling upstream of key mediators of osteoblast differentiation. Three of the 6 mutations identified in trios occurred de novo in the proband, while 3 were transmitted from unaffected parents. Patients with nonsyndromic CS were highly enriched for mutations in AXIN1 compared to both expectation (p = 0.0008) and exome sequencing data from > 76,000 healthy controls (p = 2.3 × 10-6), surpassing the thresholds for genome-wide significance. These findings describe the first phenotype associated with mutations in AXIN1, with mutations identified in approximately 1% of nonsyndromic CS cases. The results strengthen the existing link between Wnt signaling and maintenance of cranial suture patency and have implications for genetic testing in families with CS.

Concurrent Craniosynostosis and Positional Plagiocephaly: A Scoping Review

Background: Craniosynostosis and positional plagiocephaly (PP) both lead to deformities of the infant skull. In some cases, patients may present with concurrent craniosynostosis and PP. The forces exerted on the skull by both conditions can complicate and delay correct diagnosis and require adjustments to surgical planning. Objective: The purpose of this scoping review was to identify and analyze the existing peer-reviewed literature covering the diagnosis and treatment of concurrent craniosynostosis and PP. Design: In accordance with PRISMA guidelines, PubMed, MEDLINE, and EMBASE were searched for articles discussing concurrent diagnoses of craniosynostosis and PP. Results: Out of 633 articles discovered, 7 met inclusion criteria and discussed a cumulative total of 10 patients. The average age of referral to a craniofacial team was 17 ± 22.2 months. The most common reason for referral was craniofacial asymmetry (90%, n = 9). 40% presented with unilateral coronal synostosis (n = 4), 40% with lambdoid synostosis (n = 4), 10% with sagittal synostosis (n = 1), and 10% with metopic synostosis (n = 1). The most commonly reported clinical features were occipital flattening (90%, n = 9), ear displacement (80%, n = 8), and frontal bossing (30%, n = 3). Delayed or incorrect initial diagnosis was noted in 70% (n = 7) of patients. CT scan was the most commonly employed diagnostic tool, utilized in 100% of patients. 70% of patients (n = 7) underwent surgery at an average age of 6.75 ± 3 months. Two studies, accounting for 2 patients reported, noted altering their surgical technique to account for PP in addition to the synostotic suture. Conclusions: Coincident craniosynostosis and PP can pose a complicated diagnostic and therapeutic challenge. An in-depth understanding of the most reliable physical exam findings associated with each type of craniosynostosis combined with PP will facilitate accurate diagnosis. Consideration of the concurrent forces on the skull created by craniosynostosis and PP aid in the design of a tailored surgical plan.

Wnt signaling in cranial bones as a proponent of TH-induced craniosynostosis.

Craniosynostosis (CS) is the premature fusion of the sutures within the skull during embryonic development. Recently, thyrotoxicosis in pregnant women has been shown to increase the risk of craniosynostosis in the developing fetus, but the specific mechanism relating the accelerated bone development in CS to increased thyroid hormone (TH) is unknown. Different cell signaling pathways, such as Wnt, Ihh, BMP, and IGF-1, have been identified in TH regulated bone development. However, the Wnt pathway has been chosen in this study for its extensive involvement in bone development. It is known that Wnt-signaling increases levels of β-catenin which then drives the transcription of Wnt/β-catenin target genes such as Twist1 and Runx2. When upregulated, these genes have been linked to increased osteoblast differentiation and bone formation. In this study, we aimed to determine the level of Wnt signaling activation, in cranial bones of differing embryonic origins (frontal and parietal bones) from an avian model of thyrotoxicosis. Collected bones were processed for assessing β-catenin protein expression by western blotting and Twist1 and Runx2 gene expression by qRT-PCR. Analysis is currently in progress. We predict that differences will be observed between the parietal and frontal bones as the parietal bones derive from the mesoderm whereas the frontal bones derive from the neural crest.

Genetic and Protein Expression Comparison of Tissues of Differing Embryonic Origin.

Non-syndromic Craniosynostosis (CS) has an unknown etiology. The overproduction of thyroid hormones (THs) during pregnancy known as maternal hyperthyroidism has been cited by the CDC as a potential cause of CS. Elucidation of the mechanism for TH induced CS may allow for the creation of a novel more suitable treatment option. There are several signaling pathways involved in the differentiation and development of the tissues of the skull such as, BMP, Ihh, and Wnt. Wnt signaling has been linked to the differentiation of both embryonic mesoderm as well as neural crest cells, from which the relevant tissues of the skull originate. The goal of this study is to quantify and compare genetic and protein expression of relevant Wnt signaling molecules and their target genes within the Sagittal and Coronal sutures. Beta-Catenin is a Wnt signaling molecule that acts as a transcription factor modulating the expression of genes such as Runx2 and Twist1. These genes were selected as they are known to be involved in cranial development. Sutures were collected from an avian model of induced thyrotoxicosis and analyzed using qRT-PCR and western blotting. Results of the qRT-PCR showed a significant downregulation in Runx2 and Twist1 expression in the coronal sutures with no change in Twist1 and a significant upregulation of Runx2 expression in the sagittal sutures. Western blot results are still pending. While further investigation into these pathways is necessary, our findings conclude that these key pathways react differently to modulation by thyroid hormones in tissues of differing embryonic origin.

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.

Yoda1 opens the lymphatic path for craniosynostosis therapy.

The rediscovery of meningeal lymphatic vessels (MLVs) has sparked research interest in their function in numerous neurological pathologies. Craniosynostosis (CS) is caused by a premature fusion of cranial sutures during development. In this issue of the JCI, Matrongolo and colleagues show that Twist1-haploinsufficient mice that develop CS exhibit raised intracranial pressure, diminished cerebrospinal fluid (CSF) outflow, and impaired paravascular CSF-brain flow; all features that were associated with MLV defects and exacerbated pathology in mouse models of Alzheimer's disease. Activation of the mechanosensor Piezo1 with Yoda1 restored MLV function and CSF perfusion in CS models and in aged mice, opening an avenue for further development of therapeutics.

Discussion: Improved Facial and Skull-Base Symmetry following Osteotomy and Distraction of Unilateral Coronal Synostosis.

Discussion: Improved Facial and Skull-Base Symmetry following Osteotomy and Distraction of Unilateral Coronal Synostosis.

The value of genome-wide analysis in craniosynostosis.

Background: This study assessed the diagnostic yield of high-throughput sequencing methods in a cohort of craniosynostosis (CS) patients not presenting causal variants identified through previous targeted analysis. Methods: Whole-genome or whole-exome sequencing (WGS/WES) was performed in a cohort of 59 patients (from 57 families) assessed by retrospective phenotyping as having syndromic or nonsyndromic CS. Results: A syndromic form was identified in 51% of the unrelated cases. A genetic cause was identified in 38% of syndromic cases, with novel variants detected in FGFR2 (a rare Alu insertion), TWIST1, TCF12, KIAA0586, HDAC9, FOXP1, and NSD2. Additionally, we report two patients with rare recurrent variants in KAT6A and YY1 as well as two patients with structural genomic aberrations: one with a 22q13 duplication and one with a complex rearrangement involving chromosome 2 (2p25 duplication including SOX11 and deletion of 2q22). Moreover, we identified potentially relevant variants in 87% of the remaining families with no previously detected causal variants, including novel variants in ADAMTSL4, ASH1L, ATRX, C2CD3, CHD5, ERF, H4C5, IFT122, IFT140, KDM6B, KMT2D, LTBP1, MAP3K7, NOTCH2, NSD1, SOS1, SPRY1, POLR2A, PRRX1, RECQL4, TAB2, TAOK1, TET3, TGFBR1, TCF20, and ZBTB20. Conclusion: These results confirm WGS/WES as a powerful diagnostic tool capable of either targeted in silico or broad genomic analysis depending on phenotypic presentation (e.g., classical or unusual forms of syndromic CS).

Optic neuropathy in craniosynostosis.

Craniosynostosis (CS) or the premature fusion of one or more cranial sutures in utero, or during the first years of life, can present in isolation or as a multisystem clinical disorder with a particular impact on visual function. Among ophthalmic complications, optic neuropathy is a significant cause of irreversible vision loss in these patients. Children with CS are at higher risk of developing elevated intracranial pressure which can lead to papilledema and, ultimately, optic atrophy. In addition, sometimes associated obstructive sleep apnea, abnormalities in central nervous system venous development, and Chiari malformation may contribute to optic neuropathy. Ophthalmologists have an important role in managing a number of coexistent ophthalmologic complications such as strabismus, anisometropia, amblyopia, ptosis, and exposure keratopathy in addition to maintaining surveillance for early signs of optic neuropathy; they play a critical consultative role contributing to the decision for primary or repeat decompressive surgery. In this article, we aim to review the etiology, diagnostic approach, and management of optic neuropathies in patients with craniosynostosis.

Prospective assessment of surgical stress response in patients with craniosynostosis: comparison of clinical and laboratory data

Highly traumatic surgical correction of craniosynostosis (CS) is usually followed by severe postoperative period and high risk of complications. Surgical stress response (SSR) is an important and often neglected cause of severe early postoperative period. To compare clinical and laboratory parameters of SSR in children who underwent various surgeries for CS. The study included 63 patients aged 7.02±4.12 months. All ones underwent surgery for CS between October 2021 and June 2022. We analyzed clinical and laboratory markers of SSR, as well as correlation with severity of surgical stress. No surgical complications were observed. There were postoperative complications in 12 (19.0%) cases including febrile fever in 9 (14.3%) patients, severe pain and edematous syndromes with prolonged hospital-stay in 3 (4.8%) cases. Significant correlations were revealed between severity of surgical stress and certain laboratory markers (CRP, ACTH, T3, insulin, HOMA-IR). The last ones characterized SSR severity. Patients with high scores of stress response demonstrated more severe course of early postoperative period. Surgical stress scale makes it possible to predict early postoperative period and optimize patient management. Lower severity of surgical stress response following endoscopic interventions is another reason for the wider use of low-traumatic surgical methods in pediatric neurosurgery.

Диагностика и оценка эффективности хирургических методик лечения несиндромальных изолированных краниосиностозов у детей старше 2 лет на примере скафоцефалии и лобной плагиоцефалии

If craniosynostosis (CS) is not diagnosed in a timely manner, the disease develops into craniostenosis. The optimal timing for surgical correction is the first 6 to 8 months of life. However, parents of children with CS over 2 years of age often seek help. The purpose of the research was to determine the optimal diagnostic tactics, to evaluate the effectiveness of existing surgical methods for treating isolated CS in children over 2 years of age using the example of the two most common forms, sagittal and hemicoronal CS. Materials and methods used: the results of treatment of 36 pediatric patients with isolated sagittal CS and 21 with hemicoronary CS aged 2 to 7 y/o were analyzed. The control group consisted of patients with CS of the younger age group (under 2 y/o). The diagnosis used computed tomography (CT) of the skull, ophthalmoscopic examination using the RetCam device, and direct invasive monitoring of intracranial pressure. Surgical treatment included one-stage reconstructive cranioplasty, Pi-shaped craniotomy and installation of compression-distraction devices. Treatment results were assessed by calculating craniometric parameters at both pre- and postoperative stages. Statistical assessment of the effectiveness of the results of various types of surgical correction was carried out as well. Results: hypertensive changes, according to CT data, were found in all patients. Intracranial hypertension was detected in 38% of cases in children with sagittal and 33% of cases in patients with hemicoronary CS. Craniometric indices after surgical treatment were statistically better in the younger age group. Conclusion: Children over 2 years of age suffering from CS may not experience clinical manifestations of intracranial hypertension. The method of direct monitoring of intracranial pressure and assessment of the condition of the fundus allow a reliable assessment of the stage of the disease. Surgical treatment of the disease should be performed during the first year of life, which gives the best both cosmetic and functional results. In the case of treatment at a later date, the most optimal results are achieved with the use of one-stage reconstructive cranioplasty.

Intracranial Pressure, Autoregulation, and Cerebral Perfusion in Infants With Nonsyndromic Craniosynostosis at the Time of Surgical Correction

BACKGROUND AND OBJECTIVE: Although an increased intracranial pressure (ICP) is a known problem in children with syndromic craniosynostosis, it remains unclear whether elevated ICP and impaired cerebral perfusion exist in nonsyndromic synostosis and should be defined as targets of primary treatment. This study aimed to investigate ICP, cerebral autoregulation (CAR), and brain perfusion in infants with nonsyndromic craniosynostosis at first surgical intervention. METHODS: Forty-three infants were prospectively included. The patients underwent perioperative measurement of mean arterial blood pressure, ICP, and brain perfusion before and after cranial vault decompression. Physiological parameters with possible influences on ICP and autoregulation/brain perfusion were standardized for age. CAR was assessed by the pressure reactivity index (PRx), calculated using the mean arterial blood pressure and ICP. RESULTS: Biparietal decompression was performed in 29 infants with sagittal synostosis (mean age, 6.1 ± 1.3 months). Fronto-orbital advancement was performed in 10 and 4 infants with metopic and unilateral coronal synostosis, respectively (mean age, 11.6 ± 2.1 months). An elevated ICP (&gt;15 mm Hg) was found in 20 of 26 sagittal (mean, 21.7 ± 4.4 mm Hg), 2 of 8 metopic (mean, 17.1 ± 0.4 mm Hg), and 2 of 4 unilateral coronal synostosis cases (mean, 18.9 ± 2.5 mm Hg). Initial ICP was higher in sagittal synostosis than in metopic/coronal synostosis (P = .002). The postdecompression ICP was significantly reduced in sagittal synostosis cases (P &lt; .001). The relative cerebral blood flow and blood flow velocity significantly increased after decompression. Impaired CAR was found in infants with a mean ICP &gt;12 mm Hg (PRx, 0.26 ± 0.32), as compared with those with a mean ICP ≤ 12 mm Hg (PRx, −0.37 ± 0.07, P = .001). CONCLUSION: Contrary to common belief, an elevated ICP and significantly impaired CAR can exist early in single suture synostosis, particularly sagittal synostosis. Because an influence of raised ICP on long-term cognitive development is known in other diseases, we suggest that preventing increased ICP during the phase of maximal brain development may be a goal for decompressive surgery, at least for sagittal synostosis cases.