Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis

Accepted Manuscript Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis So Young Kim, M.D, Hyung-Jin Shi, So Young Lim, M.D PII:

S1010-5182(17)30269-X

DOI:

10.1016/j.jcms.2017.08.009

Reference:

YJCMS 2754

To appear in:

Journal of Cranio-Maxillo-Facial Surgery

Received Date: 6 January 2017 Revised Date:

4 July 2017

Accepted Date: 11 August 2017

Please cite this article as: Kim SY, Shi H-J, Lim SY, Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis, Journal of Cranio-Maxillofacial Surgery (2017), doi: 10.1016/j.jcms.2017.08.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis

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So Young Kim, M.D1., Hyung-Jin Shi2, So Young Lim, M.D3.

From the 1Department of Plastic and Reconstructive Surgery, Inje University Sanggye Paik

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hospital, Inje University School of Medicine, Seoul; the 3Department of Plastic Surgery,

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Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; and Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Korea

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The authors have no conflicts of interest to declare.

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There were no funding sources for this study.

Corresponding author:

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So Young Lim, M.D., Ph.D.

Departments of Plastic and Reconstructive Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. Tel.: +82-2-3410-2239; Fax: +82-2-3410-0036 E-mail: [email protected]

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Summary

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Purpose: “Secondary craniosynostosis” (SCS) refers to a loss of sutures after corrective vault

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reconstruction. There are no prior studies that comprehensively review SCS in various types

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of non-syndromic craniosynostosis. We assessed idiopathic and iatrogenic SCS using 3-

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dimensional computed tomography (3D CT). We also performed a systematic review to

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estimate the overall incidence of SCS in each craniosynostosis type, and to characterize its

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clinical features.

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Materials and Methods: We retrospectively reviewed the CT images of patients who

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underwent surgical correction of craniosynostosis for all types of craniosynostosis between

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August 1999 and December 2015. A literature search of the Medline and Ovid databases was

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conducted in October 2016 using the search term “secondary craniosynostosis.”

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Results: In our series, iatrogenic SCS was observed in all patients who had manipulated

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normal patent sutures to variable extents. Three (17.6%) cases of idiopathic SCS developed

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on sagittal sutures, and were confirmed with a 12-month follow-up CT. In a pooled analysis

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of 10 articles, overall SCS developed in 123 of 1205 patients (10.2%). Iatrogenic SCS cases

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made up 87 of 1205 cases (7.2%), whereas 38 (3.1%) were idiopathic. Idiopathic SCS most

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commonly developed at the bi-coronal suture (n = 32, 84.2%), followed by the sagittal suture

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(n = 4, 10.5%) and uni-coronal suture (n = 1, 2.6%).

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Conclusion: This is the first review not only to describe SCS in all types of non-syndromic

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craniosynostosis, but also to classify SCS into iatrogenic and idiopathic types based on the

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underlying pathogenesis.

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Keywords: secondary craniosynostosis, secondary synostosis

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INTRODUCTION

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Regardless of the surgical method, the ideal result after synostosis correction is neo-

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suture formation and maintenance of a craniectomy gap with minimal defects along the

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craniotomy line. Unfortunately, however, several authors have reported synostosis of other

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sutures that were previously patent before synostosis correction (Marucci et al., 2008; Arnaud

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et al., 2009; Adamo and Pollack, 2010; Seruya et al., 2013). For example, a representative

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case included newly developed coronal synostosis after extended sagittal strip craniectomy

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with bilateral parietal wedge osteotomies for sagittal synostosis correction (Agrawal et al.,

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2006; Cetas et al., 2013; Kuang et al., 2013; Seruya et al., 2013). In these studies, newly

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developed synostoses were called secondary craniosynostosis (SCS). Secondary

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craniosynostosis is defined as a closure in other sutures that were previously open after

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corrective vault reconstruction. In children with syndromic synostosis, SCS occurred after the

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primary surgery in 10.8-36.8% of cases due to an underlying genetic disorder frequently

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related to the fibroblast growth factor receptor gene, which affects all parts of the cranium

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(Esmaeli et al., 2014). In contrast, in patients with non-syndromic synostosis, the incidence of

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SCS after primary surgical correction varied from a few case reports to more than 80%. We

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hypothesize that the discrepancy in the incidence of SCS may be attributable to different

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types of surgical treatment and the extent of surgery. In other words, it is possible that

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previous studies reported mixed results by including both iatrogenic SCS caused by surgical

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manipulation and idiopathic SCS considered as genuine SCS that developed postoperatively

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despite non-surgical manipulation during primary surgery.

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In this study, we assessed all kinds of cranial suture patency following surgical correction

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using follow-up 3-dimensional computed tomography (3D CT). We also identified both

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iatrogenic and idiopathic SCS in 4 kinds of nonsyndromic synostoses. Furthermore, we 2

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performed a systematic review of previous literature regarding SCS to estimate the overall

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incidence of SCS for each craniosynostosis type, and investigated the characteristics of

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patients who might have had a bearing on both kinds of SCS.

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MATERIALS AND METHODS

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Patients and CT imaging for SCS

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After Institutional Review Board approval, a retrospective review was performed for

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patients who underwent surgical correction for all kinds of craniosynostosis between August

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1999 and December 2015. Patients were included if they underwent 3D craniofacial CT both

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preoperatively and at least 12 months postoperatively to confirm the quality of re-ossification

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in the craniectomy gap, and to evaluate overall cranial vault volume and morphology.

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Patients were excluded if they had a syndromic craniosynostosis, did not have a postoperative

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follow-up CT, or had a prior cranial vault reconstruction. Related demographics and surgical

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data were reviewed from the medical records. The normal sutures that were manipulated

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during surgery were identified through review of the intraoperative photographs. 3D CT scan

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images not only provided an overview of which cranial sutures were patent versus closed, but

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also revealed other signs of increased intracranial pressure, including copper beating. SCS

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was identified by comparing pre- and postoperative CT images, and was classified into either

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iatrogenic or idiopathic SCS. Iatrogenic SCS developed in the area of surgical manipulation,

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whereas idiopathic SCS occurred in areas free of surgical manipulation.

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Surgical technique

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All surgical procedures were performed by our senior author and a neurosurgeon. We performed open osteotomy designs for synostosis correction, and fixation techniques with

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resorbable plate osteosynthesis. Specifically, in early 2 cases around 2000, Biosorb (Bionx,

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Tampere, Finland) plates were used, and then a variety of geometric plate and mesh panels

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from several corporations, including Rapidsorb (Synthes, West Chester, PA, USA), Inion CPS

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(Inion, Tampere, Finland), and LactoSorb (Walter Lorenz Surgical Inc, Jacksonville, FL),

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were used and cut into multiple smaller elements as needed. For the surgical correction for

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sagittal synostosis, we performed a modified pi craniectomy with barrel stave osteotomies of

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the bi-temporal area. Bi-coronal sutures were manipulated with this procedure (Fig. 1). For

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patients with bi-coronal/uni-coronal and metopic synostosis, fronto-orbital advancement with

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or without transposition of the frontal bone flap was performed. For bi-coronal synostosis, the

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anterior part of the sagittal suture was partially manipulated. In most cases of uni-coronal

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synostosis, the previously patent contralateral coronal suture was manipulated (Fig. 2). In

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metopic synostosis, bi-coronal sutures were involved in the surgical procedure. In a few cases,

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distraction osteogenesis was used to focus on the areas of the skull with fused sutures in order

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to minimize the extent of the procedure. Therefore, there were no manipulated normal patent

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sutures after distraction osteogenesis was complete. There were no cases of lambdoid

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synostosis in this series.

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Literature review of secondary craniosynostosis

A literature search of the Medline and Ovid databases was conducted in October 2016

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using the search terms “secondary craniosynostosis,” “restenosis,” and “secondary operation.”

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A manual search was also performed to identify additional, relevant papers. A total of 318

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papers were obtained through this search. After excluding articles that were not related to 4

ACCEPTED MANUSCRIPT nonsyndromic synostosis based on a review of their titles, 50 abstracts were included. Case

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reports that reflected the incidence of SCS were also included. Studies were excluded based

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on predefined exclusion criteria (Fig. 3), which eventually yielded 10 papers for final analysis.

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The following data were extracted using a standardized data extraction form (Table 1). We

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reviewed the surgical methods established in each paper. We classified SCS based on 2 types,

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iatrogenic and idiopathic, according to the aforementioned definition. In addition, we

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investigated routine follow-up images (x-ray or CT scans). A pooled analysis of SCS

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incidence was performed. Chi-square or Fisher exact, paired-samples t, and Mann-Whitney U

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tests were conducted. A p-values <0.05 were considered statistically significant. All statistical

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analyses were conducted using SPSS 19.0 (SPSS Inc., Chicago, IL, USA).

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RESULTS

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Clinical results

In our series, after excluding 3 patients due to a lack of postoperative CT and follow-up

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loss, 17 patients (14 boys and 3 girls) met inclusion criteria. There were 4 types of

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craniosynostosis, including 8 sagittal, 3 bi-coronal, 5 uni-coronal and 1 metopic synostosis.

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Mean age at the time of surgery was 18 months (range, 6 months to 10 years), and 4 (23.5%)

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patients underwent primary synostosis correction before 6 months of age. Most patients

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underwent open craniectomies with cranial vault remodeling, and fixation using resorbable

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sutural osteosynthesis. Distraction osteogenesis was performed in 2 patients with uni-coronal

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synostosis (Table 2). Except for 2 cases of distraction osteogenesis, manipulated normal

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patent sutures were confirmed in 15 patients intraoperatively. Table 3 details the involvement

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of normal patent sutures for each patient. There were no major or permanent complications of

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surgery, including cerebrospinal fluid (CSF) leak, brain injury, infection, or hematoma. The mean follow-up period was 5.5 years. On postoperative CT scan (a minimum of 12 months to 10 years after surgery), iatrogenic SCS was observed in all patients who had

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manipulated normal patent sutures. The extent of this iatrogenic SCS varied across patients.

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Among 9 patients with bi-coronal manipulation (8 in sagittal and 1 in metopic synostosis),

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uni-coronal SCS developed in 2 patients, and bi-coronal SCS in 7 (Fig. 4). All 3 patients with

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contralateral coronal manipulation for the correction of uni-coronal synostosis developed

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partial iatrogenic contralateral coronal SCS. Among 3 patients with partial sagittal

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manipulation for surgical correction of bicoronal synostosis, partial sagittal SCS developed in

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2 patients, whereas 1 patient developed complete sagittal SCS (even in the non-manipulated

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portion of the sagittal suture) (Fig. 5). Including this complete sagittal SCS, 3 cases (17.6%)

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of idiopathic SCS developed on the sagittal suture in this study, as confirmed with 12-month

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follow-up CT (including 1 metopic shown in Fig. 6, and 1 uni-coronal and 1 bi-coronal

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synostosis). Detailed patient-related characteristics and time to develop idiopathic SCS are

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shown in Table 4. None of these 3 patients showed clinical signs of increased ICH and

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underwent a secondary operation. There was no evidence of iatrogenic or idiopathic lambdoid

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SCS in this study.

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Systematic review of literature with pooled analysis

Overall SCS incidence by craniosynostosis type

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Ten papers representing a total of 1205 patients were included in this SCS incidence

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review (Hudgins et al., 1998; Agrawal et al., 2006; Marucci et al., 2008; Arnaud et al., 2009;

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Adamo and Pollack, 2010; Cetas et al., 2013; Kuang et al., 2013; Seruya et al., 2013; Esmaeli

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et al., 2014; Yarbrough et al., 2014). Six of the 10 papers, representing 585 patients, described 6

ACCEPTED MANUSCRIPT sagittal SCS synostosis, and 1 paper included metopic synostosis. In contrast, the remaining 3

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papers described all different kinds of craniosynostosis. Most studies described open

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craniectomy with cranial vault remodeling, except 1 study, which used an endoscopic assisted

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procedure. However, synostosis correction extensiveness varied across the studies. Overall,

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SCS developed in 123 of 1205 patients (10.2%). In all, 87 of these cases were iatrogenic

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(7.2%), whereas 38 were idiopathic (3.1%). Among all patients, 2 presented with both

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iatrogenic and idiopathic SCS. (Hudgins et al., 1998) Regarding routine image follow-up, 4

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papers, representing 355 (29.4%) patients, described postoperative image follow-up for all

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patients, whereas 5 other papers did not. Total SCS incidence in the routine image follow-up

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group was significantly higher than that described in papers that did not report postoperative

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imaging (p = 0.01).

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Iatrogenic SCS

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Among 726 patients who had manipulated normal patent sutures, 87 (11.9%) developed iatrogenic SCS. In 4 studies reporting sagittal synostosis correction, bi-coronal and lambdoid

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sutures were easily manipulated to various extents. There were controversial results with

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regard to SCS in the lambdoid suture. Seruya et al. performed extensive manipulation of

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normal lambdoid sutures, including craniectomy of the sutural site and sutural movement,

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and found that 93.6% of patients developed iatrogenic SCS in uni-lambdoid sutures. In

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contrast, Kuang et al. conducted less extensive surgery at the lambdoid suture (compared to

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that performed by Seruya et al.), and found that only 13.5% of patients developed lambdoid

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SCS. In a pooled analysis of these 2 studies, the extensiveness of the surgical manipulation at

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the lambdoid suture was significantly associated with the incidence of iatrogenic lambdoid

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SCS (odds ratio = 93.86, 95% confidence interval 20.9−421.5, p = 0.00). The 2 remaining

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studies did not report use of image work-ups in their patient groups, and found 0.6% and 6.1%

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ACCEPTED MANUSCRIPT iatrogenic SCS at the coronal sutures, respectively. This low iatrogenic SCS incidence was

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also found in other primary craniosynostosis papers that did not report routine imaging

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follow-up (Table 5). After the correction of metopic synostosis, bi-coronal iatrogenic SCS

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was reported as 3 patients in 2 studies (Hudgins et al., 1998; Esmaeli et al., 2014). With the

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exception of 2 patients who had both iatrogenic and idiopathic SCS, 9 patients with

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iatrogenic SCS (10.3%) underwent secondary operations for SCS correction.

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Idiopathic SCS

Among a total of 38 patients who developed idiopathic SCS, 32 (84.2%) developed SCS

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in the primary sagittal synostosis, whereas in 4 (10.5%) cases SCS occurred in the primary

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metopic synostosis. The most common suture in which idiopathic SCS developed was bi-

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coronal (n = 32, 84.2%), followed by sagittal (n = 4, 10.5%), and uni-coronal (n = 1, 2.6%).

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There was 1 uni-coronal synostosis patient who developed secondary pancraniosynostosis

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postoperatively. We did not find any evidence in the literature for isolated idiopathic SCS in

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lambdoid sutures except the aforementioned secondary pancraniosynostosis. Regarding

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surgery-related factors, most patients with idiopathic SCS (n = 36, 94.7%) underwent open

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craniectomies. However, 2 patients who underwent endoscopic craniectomies also developed

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idiopathic SCS. A total of 33 (86.8%) idiopathic SCS patients underwent primary synostosis

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correction before 6 months of age. In all, 15 (39.4%) idiopathic SCS cases were detected

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before 18 months postoperatively based on various signs and symptoms. In particular, 2

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studies (representing 28 idiopathic SCS cases) performed postoperative imaging follow-up; in

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these studies, most cases of idiopathic SCS were diagnosed based on imaging. With the

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exception of 28 cases, there were postoperative head shape deformities in most cases. These

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changes were the initial suspicion signs for SCS. Signs and symptoms of increased

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intracranial pressure (IICP) such as headache and papilledema developed in 18 idiopathic

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SCS patients. Finally, 10 (26.3%) of all patients with idiopathic SCS underwent secondary

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surgeries with the goal of decompressing IICP, or correcting head morphology (Table 6).

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Pathogenesis and characteristics of iatrogenic SCS

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DISCUSSION

There are several possible hypotheses regarding the mechanism underlying iatrogenic

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SCS. The most plausible hypothesis suggests that SCS forms when normal patent sutures

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separate from the underlying dura. Usually, surgery or other intervention disrupts normal

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suture anatomy during cranial vault reconstruction. This manipulation interrupts the signaling

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mechanism in the dura that maintains normal patent sutures, and weakens potential

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stimulation of calvarial growth by pulsatile forces from the brain (Seruya et al., 2013).

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Ultimately, this leads to SCS development (Arnaud et al., 2009; Adamo and Pollack, 2010;

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Cetas et al., 2013). According to this study, the dura detachment theory is acceptable because

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most manipulated normal patent sutures in our patients eventually closed, although the extent

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of closure varied. Furthermore, the result of pooled analysis revealed that the more extensive

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surgical manipulation of normal sutures including separation from the underlying dura,

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fracture or craniectomy, and relocation of normal sutures increased the incidence of

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iatrogenic SCS in 2 follow-up studies representing 49 cases of iatrogenic lambdoid SCS (p <

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0.001) (Kuang et al., 2013; Seruya et al., 2013). This fact supports the hypothesis that it arises

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from the detachment of normal sutures from the underlying dura, premature fusion of normal

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sutures, and interruption of normal suture growth.

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Regarding the influence of fixation technique on iatrogenic SCS, with the recent advent

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of the resorbable osteosynthesis system, a variety of plates and meshes have become widely 9

ACCEPTED MANUSCRIPT used for cranial vault reshaping instead of metallic wire or titanium plates. Based on the

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concept that these biodegradable osteosynthesis materials form a membrane that guides bone

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regeneration, we usually cover the major part of osteotomy lines with several meshes to

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further stabilize bone fragments and provoke bone regeneration between the bony gaps as

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previously reported in the literature. Interestingly, we observed that most patients who

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received extensive osteosynthesis with meshes showed complete iatrogenic SCS, whereas in

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2 patients who received only limited osteosynthesis with absorbable plates, partial iatrogenic

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SCS was reported. Although an analysis by fixation technique and iatrogenic SCS could not

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be performed because of the lack of specific data on fixation technique type used for

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osteosynthesis in the literature review and the small sample size of the present study, we

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assumed that extensive fixation techniques using mesh could be a risk factor for iatrogenic

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SCS; further studies related to this issue are required in the future.

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The literature is not conclusive and demonstrates conflicting data regarding whether

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certain suture types are more prone to develop iatrogenic SCS if a normal suture is insulted.

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Seruya et al. reported that lambdoid sutures have a higher propensity to develop iatrogenic

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SCS than do coronal sutures. In contrast, Kuang et al. found that iatrogenic SCS developed

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more commonly at the coronal suture than it did at the lambdoid suture (Kuang et al., 2013;

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Seruya et al., 2013). It is difficult to determine which suture is more likely to develop

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iatrogenic SCS by simply comparing the incidence of iatrogenic SCS. There are several

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important factors that should be considered, including the architectural differences between

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sutures. In addition, it is important to consider the differential degree of surgical manipulation

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at each suture. Therefore, a controlled study that considers these factors is needed to further

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investigate the incidence of iatrogenic SCS.

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Interestingly, the rate of secondary surgeries for the correction of iatrogenic SCS was

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approximately 10%. This was much lower than that for idiopathic SCS (26.3%) in the pooled 10

ACCEPTED MANUSCRIPT analysis despite a higher incidence of iatrogenic SCS (7.2%) than idiopathic SCS (3.1%). In

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our experience, even if iatrogenic SCS developed at 100% of manipulated suture sites,

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normal growth was frequently observed, and secondary corrective surgeries were not often

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required. These findings may be attributable to the craniectomy gap adjacent to the fused

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suture, and the role it played in maintaining the intracranial space and minimizing the effect

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of iatrogenic SCS.

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Pathogenesis and characteristics of idiopathic SCS

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There are several, controversial theories regarding the pathogenesis of idiopathic SCS. One hypothesis involves intrinsic suture pathology and an abnormal signal from the cranial

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base that spreads to the calvarium based on genetic or metabolic causes (Moss, 1975).

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Therefore, when the underlying abnormal cranial base remains, either recurrent synostosis

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may develop after correction, or late onset SCS may occur in a previously open suture. This

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theory seems to apply to syndromic craniosynostosis because of the involvement of the

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midface and the high incidence of both recurrent synostosis and SCS. This hypothesis also

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explains some, but not all, cases of idiopathic SCS. We suspect that there is compensatory

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brain growth toward the area of increased dead space, which is caused by primary synostosis

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correction. An abrupt decrease and delay in brain growth perpendicular to the primary

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synostosis may subsequently cause premature suture fusion. In particular, after correction of

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bi-coronal synostosis, during which the antero-posterior (AP) dimension of the cranial vault

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was increased, there was delayed compensatory internal brain growth in the bi-temporal

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direction. Subsequently, sagittal idiopathic SCS could develop. A similar concept has been

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suggested in the literature describing post−ventricular shunting SCS. Decreased intracranial

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volume resulted in over-drainage of the cerebrospinal fluid. Alternatively, delayed internal

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ACCEPTED MANUSCRIPT brain growth after shunting could lead to collapse of the cranial vault with apposition, or

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overriding sutures and subsequent synostosis (Shuster et al., 1995; Park et al., 2009). In our

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study, idiopathic SCS developed in the sagittal suture in 3 patients who underwent surgery to

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widen the AP dimension. We did not detect idiopathic SCS in the bi-coronal suture because of

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frequent surgical manipulation of this suture during bi-temporal widening surgery. However,

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pooled analysis demonstrated 32 (84.2%) cases of idiopathic SCS in the bi-coronal suture in

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patients who underwent all bi-temporal widening surgery for sagittal synostosis correction.

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There may be few or no cases of idiopathic SCS after distraction osteogenesis, during which

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the cranium is gradually expanded postoperatively, allowing a slow expansion of the brain

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and less dead space between the brain and cranium. There are currently no studies addressing

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the development of idiopathic SCS after DO procedures for the correction of non-syndromic

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synostosis. Therefore, further study in this area is needed.

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SCS identification on imaging follow-up

With the advancement of 3D photography in recent years, the use of follow-up CT

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imaging during postoperative periods has come under increasing scrutiny. Because most of

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the reasons for a secondary surgery were poor appearance and intracranial pressure increase,

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CT may be likely to be abandoned in many craniofacial centers for follow-up. Of course, we

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agree that unnecessary radiation and examinations should be avoided; however, it is not

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possible to identify iatrogenic and idiopathic SCS without documentation of suture patency

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using preoperative and postoperative imaging. According to pooled analysis, 2 studies that

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reported pre- and postoperative CT scans found that more than 80% of patients who

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underwent coronal suture manipulation developed iatrogenic SCS (Kuang et al., 2013; Seruya

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et al., 2013). In addition, of all idiopathic SCS cases, 70% were diagnosed through routine

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ACCEPTED MANUSCRIPT imaging follow-up. The detection of idiopathic SCS is particularly important with regard to

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prognosis; 30% of idiopathic SCS cases required subsequent corrective surgeries in the

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pooled analysis. Fortunately, there are now low-radiation techniques that are available. We

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advocate a protocol of prospective routine radiographic follow-up with low-dose radiation

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after primary cranial vault repair for non-syndromic synostosis, and this ought to be used

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judiciously to provide pertinent information for patient care. However, there is still no

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consensus regarding how often and for how long radiologic follow-up should be performed.

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The interval and period of imaging follow-up should be determined based on time to develop

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SCS. According to the aforementioned hypothesis, idiopathic SCS develops early and is

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sensitive to volume changes in the intracranial environment. In this study, idiopathic SCS was

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discovered in 3 patients at postoperative CT follow-up before 18 months, which is the period

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of postoperative cranial stabilization, as suggested by Barone and Jimenez et al. (2011)

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However, the pooled analysis data revealed a similar incidence of idiopathic SCS diagnosed

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before and after 18 months. This discrepancy may be explained by the fact that some prior

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studies used routine imaging, whereas others did not. Further objective studies are needed to

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clarify these findings.

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Our findings should be interpreted in the light of several limitations. Although we tried to include only non-syndromic synostosis, there is a slight possibility that syndromic patients

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were not totally excluded from the pooled analysis. Furthermore, large prospective studies or

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systematic reviews are required to substantiate our conclusions.

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CONCLUSION To the best of our knowledge, this is the first study that not only characterizes SCS for all

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types of non-syndromic craniosynostosis, but also specifically classifies SCS into iatrogenic

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and idiopathic types. The results of this study provide insight into the fate of sutures in 13

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patients with non-syndromic synostosis and subsequent synostosis correction.

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Arnaud E, Capon-Degardin N, Michienzi J, Di Rocco F, Renier D: Scaphocephaly part II: secondary coronal synostosis after scaphocephalic surgical correction. J Craniofac Surg

335

20 Suppl 2: 1843-1850, 2009

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334

Cetas JS, Nasseri M, Saedi T, Kuang AA, Selden NR: Delayed intracranial hypertension after

337

cranial vault remodeling for nonsyndromic single-suture synostosis. J Neurosurg

338

Pediatr 11: 661-666, 2013

340 341

Esmaeli A, Nejat F, Habibi Z, El Khashab M: Secondary bicoronal synostosis after metopic craniosynostosis surgical reconstruction. J Pediatr Neurosci 9: 242-245, 2014 Hudgins RJ, Cohen SR, Burstein FD, Boydston WR: Multiple suture synostosis and

EP

339

TE D

336

increased intracranial pressure following repair of single suture, nonsyndromal

343

craniosynostosis. Cleft Palate Craniofac J 35: 167-172, 1998

344

AC C

342

Kuang AA, Jenq T, Didier R, Moneta L, Bardo D, Selden NR: Benign radiographic coronal

345

synostosis after sagittal synostosis repair. J Craniofac Surg 24: 937-940, 2013

346

Marucci DD, Johnston CP, Anslow P, Jayamohan J, Richards PG, Wilkie AO, et al:

347

Implications of a vertex bulge following modified strip craniectomy for sagittal

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synostosis. Plast Reconstr Surg 122: 217-224, 2008

349

Moss ML: Functional anatomy of cranial synostosis. Childs Brain 1: 22-33, 1975

350

Park DH, Chung J, Yoon SH: The role of distraction osteogenesis in children with secondary 15

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craniosynostosis after shunt operation in early infancy. Pediatr Neurosurg 45: 437-445,

352

2009

353

Ridgway EB, Berry-Candelario J, Grondin RT, Rogers GF, Proctor MR: The management of sagittal synostosis using endoscopic suturectomy and postoperative helmet therapy. J

355

Neurosurg Pediatr 7: 620-626, 2011

356

RI PT

354

Seruya M, Tan SY, Wray AC, Penington AJ, Greensmith AL, Holmes AD, et al: Total cranial vault remodeling for isolated sagittal synostosis: part I. Postoperative cranial suture

358

patency. Plast Reconstr Surg 132: 602e-610e, 2013

360 361

Shuster BA, Norbash AM, Schendel SA: Correction of scaphocephaly secondary to

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SC

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ventricular shunting procedures. Plast Reconstr Surg 96: 1012-1019, 1995 Yarbrough CK, Smyth MD, Holekamp TF, Ranalli NJ, Huang AH, Patel KB, et al: Delayed synostoses of uninvolved sutures after surgical treatment of nonsyndromic

363

craniosynostosis. J Craniofac Surg 25: 119-123, 2014

AC C

EP

TE D

362

16

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Figure 1. Manipulation of bi-coronal suture during surgical correction of sagittal synostosis.

366

Figure 2. Manipulation of contralateral coronal suture during surgical correction of uni-

368

coronal synostosis.

RI PT

367

369

Figure 3. Study attrition diagram.

SC

370 371

Figure 4. Preoperative 3D-CT image of sagittal synostosis (right) and iatrogenic secondary

373

synostosis developed in bi-coronal suture after sagittal synostosis correction (left).

M AN U

372

374

Figure 5. Preoperative (right) and postoperative (left) 3D-CT image of patient number 11 that

376

revealed idiopathic secondary synostosis in the sagittal suture after surgical correction of bi-

377

coronal synostosis.

378

TE D

375

Figure 6. Preoperative (right), postoperative (middle) 3D-CT, and intraoperative (left) image

380

of patient number 17 who showed iatrogenic secondary bi-coronal synostosis and idiopathic

381

secondary synostosis in the sagittal suture after surgical correction for metopic synostosis and

382

intraoperative image of bone flap fixation.

AC C

EP

379

17

ACCEPTED MANUSCRIPT Table 1. Data extraction form Study characteristics Study name First author Published year

RI PT

Institution Patient number Kinds of primary craniosynostosis

Sagittal, bicoronal, unicoronal, metopic and lambdoid synostosis Routine image follow up (x-ray, CT scan)

SC

Time of primary surgery Before 6 months Kinds of surgery

M AN U

After 6 months Open craniectomy with/without cranial vault remodeling Open craniectomy with DO Endoscopic assisted Spring assisted

Presence of manipulated normal suture during surgery Kinds of SCS

TE D

SCS number and incidence

Type of SCS Iatrogenic SCS Idiopathic SCS

EP

Sagittal, bicoronal, unicoronal, metopic and lambdoid SCS

Associated symptom of SCS

AC C

Time interval to develop the SCS

Rate of secondary operation for correction of SCS

CT; computed tomography; DO, distraction osteogenesis; SCS, secondary craniosynostosis.

ACCEPTED MANUSCRIPT Table 2 Patient demographics and surgery-related data. Variable

n (%)

Sex 14 (82.3)

RI PT

Male Female

3 (17.6)

Kinds of craniosynostosis

8 (47)

Bi-coronal

3 (17.6)

SC

Sagittal

Uni-coronal

5 (29.4)

1 (5.8)

M AN U

Metopic Time at primary surgery <6 months after birth

4 (23.5)

>6 months after birth

13 (76.4)

Kinds of surgery

TE D

Open craniectomy with cranial vault remodeling

AC C

EP

Open craniectomy and distraction osteogenesis

15 (88.2) 2 (11.7)

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Table 3. Presence of manipulated normal patent sutures and development of secondary craniosynostosis (SCS). Procedure for craniosynostosis correction

Kinds of primary synostosis

Location of normal suture

1

Sagittal

Modified pi craniectomy with barrel stave osteotomies

2

Sagittal

Modified pi craniectomy with barrel stave osteotomies

3

Sagittal

Modified pi craniectomy with barrel stave osteotomies

4

Sagittal

5

manipulated

RI PT

Patient no.

Origin iatrogenic SCS

of

Origin of idiopathic SCS

Uni-coronal

-

Bi-coronal

Bi-coronal

-

Bi-coronal

Uni-coronal

-

Modified pi craniectomy with barrel stave osteotomies

Bi-coronal

Bi-coronal

-

Sagittal

Modified pi craniectomy with barrel stave osteotomies

Bi-coronal

Bi-coronal

-

6

Sagittal

Modified pi craniectomy with barrel stave osteotomies

Bi-coronal

Bi-coronal

-

7

Sagittal

Modified pi craniectomy with barrel stave osteotomies

Bi-coronal

Bi-coronal

-

8

Sagittal

Modified pi craniectomy with barrel stave osteotomies

Bi-coronal

Bi-coronal

-

9

Bi-coronal

Fronto-orbital advancement with bone flap transposition

Partial sagittal

Partial sagittal

-

Bi-coronal

Fronto-orbital advancement with bone flap transposition

Partial sagittal

Partial sagittal

-

11

Bi-coronal

Fronto-orbital advancement with bone flap transposition

Partial sagittal

Partial sagittal

Sagittal

12

Uni-coronal

Fronto-orbital advancement with bone flap transposition

Contra-lateral uni-coronal

Uni-coronal

-

13

Uni-coronal

Fronto-orbital advancement with bone flap transposition

Contra-lateral uni-coronal

Uni-coronal

-

14

Uni-coronal

Contra-lateral uni-coronal

Uni-coronal

Partial sagittal

15

Uni-coronal

Distraction osteogenesis

None

-

-

16

Uni-coronal

Distraction osteogenesis

None

-

-

17

Metopic

Fronto-orbital advancement with bone flap transposition

Bi-coronal

Bi-coronal

Sagittal

M AN U

TE D

EP

Fronto-orbital advancement with bone flap transposition

AC C

10

SC

Bi-coronal

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Table 4

Age at primary surgery (mo)

Sex

11

Bi-coronal

Sagittal

M

10

14

Uni-coronal

Partial sagittal

F

13

17

Metopic

Sagittal

M

6

Cranial vault remodeling

AC C

EP

TE D

CT, computed tomography; F, female; M, male.

Kinds of surgery

SC

Location of SCS developed

M AN U

Patients Kinds of primary no. craniosynostosis

RI PT

Characteristics of patients with idiopathic secondary craniosynostosis (SCS). Interval to develop idiopathic SCS (CT) 12 months +

Cranial vault remodeling

+

Cranial vault remodeling

+

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Table 5. Characteristics of the 10 included studies.

Hudgins et al. (1997) Agrawal et al. (2006) Adamo et al. (2010) Seruya et al. (2013) Kuang et al. (2013) Esmaeli et al. (2014) Cetas et al. (2013)

Kinds of synostosis with SCS (n)

Presence of manipulated normal suture

Total SCS (%)

Iatrogenic SCS

Idiopathic SCS

Routine image follow-up

Retrospective

229

Open

Sagittal

Sagittal

No

24 (10.4%)

-

24 (10.4%)

Yes (x-ray)

Retrospective

87

Open

Sagittal

Sagittal

No

3 (3.4%)

-

3 (3.4%)

No

Retrospective

145

Open

All

3 (2.0%)

-

3 (2.0%)

N/S

121

Endoscopic

All

Case report

210

Open

All

Retrospective

42

Open

Retrospective

143

Retrospective

SC

RI PT

Kinds of synostosis in total patients

Bicoronal(1), Metopic(2) Metopic(1) Sagittal(1) Metopic(1) Unicoronal(1)

No

2 (1.6%)

-

2 (1.6%)

N/S

Yes

2 (0.9%)

2 (0.9%)

2 (0.9%)

No

Sagittal

Sagittal

No

4 (9.5%)

4 (9.5%)

Yes (x-ray)

Open

Sagittal

Sagittal

Yes

1 (0.6%)

1 (0.6%)

-

No

47

Open

Sagittal

Sagittal

Yes

44 (93.6)*

44 (93.6%)

-

Yes (CT)

Retrospective

37

Open

Sagittal

Sagittal

Yes

33 (89%)†

33 (89%)

-

Yes (CT)

Case report

63

Open

Metopic

Metopic

Yes

2 (3.1%)

2 (3.1%)

-

No

Retrospective

81

Open

All

Sagittal

Yes

5 (6.1%)

5 (6.1%)

Yes

M AN U

Yarbrough et al. (2014)

Primary surgery

TE D

(2008)

Patient no.

EP

Arnaud et al. (2009) Marucci et al.

Design

AC C

Study (year)

-

No

CT, computed tomography; N/S, not stated; SCS, secondary craniosynostosis. *This study reported the data of SCS incidence as right and left side in coronal and lambdoid suture each other, so total incidence of SCS cannot be extracted and the data in this table is the incidence of SCS in left lambdoid which is most highest value in that study. †This study reported additionally 5 (15%) patients with partial lambdoid synostosis.

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AC C

EP

TE D

M AN U

SC

RI PT

‡Among 5 SCS patients in this study, 2 patients were excluded because they had genetic mutation representing syndromic craniosynostosis.

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Table 6. Characteristics of iatrogenic secondary craniosynostosis (SCS). Manipulated normal patent sutures

Iatrogenic SCS (n, % of total patients in each study)

RI PT

Primary craniosynostosis

Adamo et al. (2010) Seruya et al. (2013)

Bi-coronal

Uni-coronal (n=1, %)

Contralateral coronal

Esmaeli et al. (2014) Hudgins et al. (1997)

Bi-coronal (n=2, 3.1%) Bi-coronal (n=1, 0.4%)

Hudgins et al. (1997)

Uni-coronal (n=1, 0.4%)

Kuang et al. (2013)

AC C

EP

TE D

Metopic (n=3, %)

Cetas et al. (2013)

SC

Bi-coronal and lambdoid

M AN U

Sagittal (n=83, %)

Bi-coronal (n=1, 0.6%) Uni-coronal (n=38, 81.9%) Uni-lambdoid (n=44, 93.6%) Bi-coronal (n=33, 89%) Lambdoid (n=5, 13.5%) Bi-coronal (n=5, 6.1%)

ACCEPTED MANUSCRIPT Table 7. Characteristics of 38 idiopathic secondary craniosynostosis (SCS) patients. Characteristics

N (%)

Location of SCS developed

Metopic Bi-coronal Uni-coronal Sagittal

4 (10.5%) 32 (84.2%) 1 (2.6%) 4 (10.5%)

SC

Pancranio Open craniectomy Endoscopic craniectomy <6 months

M AN U

Surgical method Age at the primary surgery

32 (84.2%) 1 (2.6%) 1 (2.6%)

RI PT

Kinds of primary craniosynostosis

Sagittal Bi-coronal Uni-coronal

>6 months Average time interval to develop the Before 18 months SCS postoperatively After 18 months

Associated symptoms and signs of IICP

EP

Rate of secondary operation for SCS

AC C

IICP, increased intracranial pressure.

5 (13.1%) 15 (39.4%) 23 (60.5%)

Imaging diagnosis Craniofacial asymmetry Vertex bulging Decreased head circumference

28 (73.6%) 5 (13.1%) 3 (7.8%) 2 (5.2%)

Headache Papilledema IICP

9 (23.6%) 2 (5.2%) 7 (18.4%)

TE D

Initial sign of idiopathic SCS

1 (2.6%) 36 (94.7%) 2 (5.2%) 33 (86.8%)

10 (26.3%)

AC C

EP

TE D

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