Bilateral Coronal Suture Synostosis Research Articles

Posterior cranial vault distraction osteogenesis in craniosynostosis: estimated increases in intracranial volume

To study distraction osteogenesis of the posterior cranial vault in children requiring increased intracranial volume. Ten patients were treated with cranial distractors. Five children had previously been operated for scaphocephaly and one child for Saether-Chotzen syndrome. Two patients had bilateral coronal suture synostosis with Muenke syndrome and two patients had Apert syndrome. At surgery, the cranial bones were mobilized, the head was widened during surgery, and the segments fixed to each other with distractors. Further expansion at a rate of 1 mm/day was performed over 2-4 weeks. The cranium was distracted posteriorly from 20 to 30 mm. The patients all tolerated surgery and distraction well. In all cases, the parents were able to perform the distraction at home. There were no technical problems with the distraction devices. Two cases had minor cutaneous problems, where the distractor penetrated the skin. These cases responded to gentle local wound care measures. At the time of distractor removal, ossification had occurred sufficiently in one of these two cases. In the other case, the device was removed and replaced with a resorbable plate, without any harmful effect on the result. In all cases, sufficient expansion was achieved without causing more cosmetic deformity. Ossification occurred in all cases. This method seems effective, as the calculated increase in intracranial volume was a mean of 20.2% (range 10.2-28.5%). This preliminary series shows that cranial bone distraction is a useful method for cranial expansion with low morbidity in children with craniosynostosis.

Noggin Inhibits Postoperative Resynostosis in Craniosynostotic Rabbits

Inhibition of bone formation after surgery to correct craniosynostosis would alleviate the need for secondary surgeries and decrease morbidity and mortality. This study used a single dose of Noggin protein to prevent resynostosis and improve postoperative outcomes in a rabbit model of craniosynostosis. Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures, which causes secondary deformations of the cranial vault, cranial base, and brain. Current surgical intervention involves extirpation of the fused suture to allow unrestricted brain growth. However, resynostosis of the extirpated regions often occurs. Several bone morphogenetic proteins (BMPs), well-described inducers of ossification, are involved in bone healing. This study tested the hypothesis that a postoperative treatment with Noggin, an extracellular BMP inhibitor, can inhibit resynostosis in a rabbit model of human familial nonsyndromic craniosynostosis. Thirty-one New Zealand white rabbits with bilateral coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 13); (2) suturectomy with BSA in a slow-resorbing collagen vehicle, (n = 8); and (3) suturectomy with Noggin in a slow-resorbing collagen vehicle (n = 10). At 10 days of age, a 3 x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with BSA-loaded gel or Noggin-loaded gel, respectively. Serial 3D-CT scan reconstructions of the defects and standard radiographs were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histological analysis. Radiographic analysis revealed that Noggin-treated animals had significantly greater coronal suture marker separation by 25 days and significantly greater craniofacial length at 84 days of age compared with controls. 3D-CT analysis revealed that Noggin treatment led to significantly greater defect areas through 84 days and to increased intracranial volumes at 84 days of age compared with other groups. Histological analysis supported CT data, showing that the untreated and BSA-treated groups had significant healing of the suturectomy site, whereas the Noggin-treated group had incomplete wound healing. These data support our hypothesis that inhibition of BMP activity using Noggin may prevent postoperative resynostosis in this rabbit model. These findings also suggest that Noggin therapy may have potential clinical use to prevent postoperative resynostosis in infants with craniosynostosis.

Anti-TGF-??2 Antibody Therapy Inhibits Postoperative Resynostosis in Craniosynostotic Rabbits

Postoperative resynostosis is a common clinical finding. It has been suggested that an overexpression of transforming growth factor (TGF)-beta2 may be related to craniosynostosis and may contribute to postoperative resynostosis. Interference with TGF-beta2 function with the use of neutralizing antibodies may inhibit resynostosis. The present study was designed to test this hypothesis. New Zealand White rabbits with bilateral coronal suture synostosis were used as suturectomy controls (group 1, n = 9) or given suturectomy with nonspecific, control immunoglobulin G antibody (group 2, n = 9) or suturectomy with anti-TGF-beta2 antibody (group 3, n = 11). At 10 days of age, a 3 x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slowly resorbing collagen gel mixed with either immunoglobulin G (100 mug per suture) or anti-TGF-beta2 (100 mug per suture). Three-dimensional computed tomography scan reconstructions of the defects were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histomorphometric analysis. Computed tomography scan data revealed that the suturectomy sites treated with anti-TGF-beta2 showed significantly (p < 0.05) greater areas through 84 days of age compared with controls. Histomorphometry also showed that suturectomy sites treated with anti-TGF-beta2 had patent suturectomy sites and more fibrous tissue in the defects compared with sites in control rabbits and had significantly (p < 0.001) less new bone area (by approximately 215 percent) in the suturectomy site. These data support the initial hypothesis that interference with TGF-beta2 function inhibited postoperative resynostosis in this rabbit model. They also suggest that this biologically based therapy may be a potential surgical adjunct to retard postoperative resynostosis in infants with craniosynostosis.

Postoperative Anti-Tgf-β2 Antibody Therapy Improves Intracranial Volume and Craniofacial Growth in Craniosynostotic Rabbits

Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-beta2 (Tgf-beta2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-beta2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n=9); 2) suturectomy with nonspecific, control IgG antibody (n=9); and 3) suturectomy with anti-Tgf-beta2 antibody (n=11). At 10 days of age, a 3 mm x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 microg/suture) or anti-Tgf-beta2 (100 microg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P<0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. Cephalometric analysis revealed significant (P<0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. These data support the initial hypothesis that interference with Tgf-beta2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.

Intracranial pressure changes in craniosynostotic rabbits.

Cranial vault and brain deformities in individuals with craniosynostosis are thought to result, in part, from changes in intracranial pressure, but clinical findings are still inconclusive. The present study describes intracranial pressure changes in a rabbit model with naturally occurring, uncorrected coronal suture synostosis. Longitudinal and cross-sectional intracranial pressure data were collected from 241 New Zealand White rabbits, divided into four groups: normal controls (n = 81); rabbits with delayed-onset coronal suture synostosis (n = 78); rabbits with early-onset unilateral coronal suture synostosis (n = 32); and rabbits with early-onset bilateral coronal suture synostosis (n = 50). Epidural intracranial pressure measurements were obtained at 10, 25, 42, and 84 days of age using a NeuroMonitor microsensor transducer. Normal rabbits and rabbits with delayed-onset coronal suture and early-onset unilateral coronal suture synostosis showed a similar oscillating pattern of age-related changes in normal and head-down intracranial pressure from 10 to 84 days of age. In contrast, rabbits with early-onset bilateral coronal suture synostosis showed markedly elevated normal and head-down intracranial pressure levels from 10 to 25 days and showed a different pattern through 84 days. Results from one-way analysis of variance revealed significant (p < 0.01) group differences only at 25 days of age. Rabbits with early-onset bilateral coronal suture synostosis had significantly (p < 0.05) greater normal and head-down intracranial pressure (by 42 percent) than the other three groups. These results showed differing intracranial pressure compensations in rabbits with uncorrected multiple-suture synostosis compared with normal rabbits or rabbits with uncorrected single-suture synostosis, possibly through progressive cerebral atrophy and decreased intracranial volume, abnormal intracranial vascular patterns and blood volume, and/or differing cranial vault compensatory changes.

Endocranial Vascular Patterns in a Familial Rabbit Model of Coronal Suture Synostosis

Abstract Objective: The present study investigates the potential relationship between craniosynostosis and any changes in endocranial vasculature. The hypothesis that crania from rabbits with familial, nonsyndromic coronal suture synostosis and crania from rabbits with experimental immobilization of the coronal suture are associated with altered form of the middle meningeal vessels and dural venous sinuses is tested. Design: Silicone rubber endocasts from 14 adult New Zealand white rabbits (Oryctolagus cuniculus) with familial nonsyndromic coronal suture synostosis (five with bilateral coronal suture synostosis and nine with unilateral coronal suture synostosis) were made to assess middle meningeal vessel and dural venous sinus form. For comparative purposes, endocasts were made from 25 rabbits with normal, patent coronal sutures and 10 rabbits with experimental immobilization of the coronal suture. Impressions of the dural venous sinuses were assessed for depth and width. The area of the confluens of sin...

Correction of Coronal Suture Synostosis Using Suture and Dura Mater Allografts in Rabbits With Familial Craniosynostosis

Abstract Objective: Resynostosis following surgical correction of craniosynostosis is a common clinical correlate. Recent studies suggest that the dura mater is necessary to maintain suture patency. It has also been hypothesized that dura mater from synostotic individuals may provide aberrant biochemical signals to the osteogenic fronts of the calvaria, which result in premature suture fusion and subsequent resynostosis following surgery. This study was designed to test this hypothesis by surgically manipulating the coronal suture and dura mater in rabbits with familial craniosynostosis to prevent postsurgical resynostosis. Design: Craniofacial growth and histomorphometric data were collected from 129 rabbits: 72 normal controls and 57 rabbits with bilateral coronal suture synostosis (15 unoperated on controls; 13 surgical controls; 9 dura mater transplant only; 10 suture transplant only; and 10 suture and dura mater transplant). At 10 days of age, all rabbits had radiopaque amalgam markers placed on eith...

Correction of coronal suture synostosis using suture and dura mater allografts in rabbits with familial craniosynostosis.

Resynostosis following surgical correction of craniosynostosis is a common clinical correlate. Recent studies suggest that the dura mater is necessary to maintain suture patency. It has also been hypothesized that dura mater from synostotic individuals may provide aberrant biochemical signals to the osteogenic fronts of the calvaria, which result in premature suture fusion and subsequent resynostosis following surgery. This study was designed to test this hypothesis by surgically manipulating the coronal suture and dura mater in rabbits with familial craniosynostosis to prevent postsurgical resynostosis. Craniofacial growth and histomorphometric data were collected from 129 rabbits: 72 normal controls and 57 rabbits with bilateral coronal suture synostosis (15 unoperated on controls; 13 surgical controls; 9 dura mater transplant only; 10 suture transplant only; and 10 suture and dura mater transplant). At 10 days of age, all rabbits had radiopaque amalgam markers placed on either side of the coronal, frontonasal, and anterior lambdoidal sutures. At 25 days of age, 42 synostosed rabbits had a 3 to 5-mm wide coronal suturectomy. Coronal sutures and/or underlying dura mater allografts were harvested from same-aged, wild-type, isohistogenic control rabbits and transplanted onto the dura mater of synostosed host rabbits. Serial radiographs were taken at 10, 25, 42, and 84 days of age, and the suturectomy sites were harvested at 84 days of age in 44 rabbits and serially sectioned for histomorphometric examination. Results revealed that cranial vault growth was significantly (p < .05) improved following surgical release of the fused coronal suture compared with synostosed rabbits who were not operated on but was still significantly different (p < .05) from that of normal control rabbits. By 84 days of age, significant (p < .05) differences were noted in calvarial suture marker separation, cranial vault shape indices, and cranial base angles between rabbits with and without dura mater allografts, probably as a result of resynostosis of the suturectomy site or suture-only allografts. Qualitative histological examination revealed that at 84 days of age rabbits with suture and dura allografts had patent coronal sutures, suture-only allografts had fused coronal sutures with extensive endosteal hyperostosis, dura mater-only allografts had some new bone in the suturectomy site that resembled rudimentary osteogenic fronts, and suturectomy controls had extensive endosteal bone formation and resynostosis of the suturectomy site. Significantly (p < .05) more bone was found in the suturectomy sites of rabbits without dura mater allografts compared with rabbits with dura mater allografts. Results support the initial hypothesis that normal dura mater allografts will maintain suture or suturectomy site patency and allow unrestricted craniofacial growth. However, it is still unclear whether the dura mater from normal rabbits was providing biochemical signals to the transplanted sutures or suturectomy sites or simply acting as a barrier to prevent abnormal biochemical signals from the dura mater of synostosed rabbits from reaching the calvaria. The clinical and therapeutic implications of these procedures are discussed.

Age-Related Changes in Intracranial Pressure in Rabbits with Uncorrected Familial Coronal Suture Synostosis

Abstract Objective: Chronic, elevated intracranial pressure (ICP) in craniosynostotic infants may result in ocular and neurocapsular problems; however, not all infants exhibit elevated ICP. Clinical ICP studies are further confounded by small and heterogeneic samples, multiple-suture involvement, and varying surgical management protocols. The present study was designed to describe longitudinal changes in ICP in a large, homogenous sample of rabbits with uncorrected familial, nonsyndromic coronal suture synostosis. Methods: Ninety-one rabbits were divided into four groups: (1) normal rabbits (n = 28), (2) rabbits with delayed-onset coronal suture synostosis (DOCS; n = 25), (3) rabbits with unilateral coronal suture synostosis (UCS; n = 12), and (4) rabbits with bilateral coronal suture synostosis (BCS; n = 26). ICP was measured at 24 and 42 days of age using a Codman epidural microtransducer. Results: Rabbits with BCS had a significantly (p < .05) higher mean ICP at 25 days of age than rabbits in the other...

Increased intracranial pressure after coronal suturectomy in craniosynostotic rabbits.

It has been suggested that the complications associated with intracranial hypertension in craniosynostotic infants may be managed with surgical release of the synostosed sutures. However, both postoperative increases and decreases in intracranial pressure (ICP) have been reported in heterogeneous samples of infants with syndromic and nonsyndromic craniosynostoses. The present study was designed to describe longitudinal changes in ICP in a homogeneous sample of rabbits with uncorrected and corrected familial coronal suture synostosis and compare them with age-matched normal control rabbits. Fifty-three rabbits were divided into three groups: normal rabbits (n = 28), rabbits with uncorrected bilateral coronal suture synostosis (n = 9), and rabbits with bilateral coronal suture synostosis with coronal suturectomy at 25 days of age (n = 16). ICP was measured at 25 and 42 days of age using a Codman epidural microtransducer. Results revealed that rabbits with uncorrected craniosynostosis had significantly (P < 0.05) higher ICP at 25 days of age than normal control rabbits by approximately 86%. However, by 42 days of age, ICP in normal rabbits increased by 75%, whereas ICP in rabbits with uncorrected craniosynostosis decreased by 69% over the same time. Synostotic rabbits with coronal suturectomy showed a 50% decrease in ICP immediately after surgical release and then followed the normal, age-related ICP pattern, which significantly increased by 75% at 42 days of age. Results suggest that, in the rabbit model, the postsuturectomy rise in ICP may simply be normal, age-related changes, although a longer follow-up will be needed to determine the recurrence of pathological ICP. Possible multifactorial explanations for intracranial decompression and compensation in the craniosynostotic rabbit model are also discussed.

Congenital Bilateral Coronal Suture Synostosis in a Rabbit and Craniofacial Growth Comparisons with Experimental Models

Experimental rabbit models of postnatal coronal suture (CS) synostosis have helped make significant contributions towards the understanding and surgical management of human congenital craniosynostosis. The present study compares craniofacial growth patterns in animals with experimental CS immobilization and in a rabbit born in our laboratory with congenital CS synostosis. The study sample consisted of 10 sham controls, 14 experimental animals with bilateral CS immobilization, and one animal with congenital, bilateral CS synostosis. At 1.5 weeks of age, all animals had amalgam markers placed on either side of the frontonasal, coronal, and anterior lambdoid sutures. At this time, the experimental animals had bilateral CS immobilization using methyl-methacrylate. Serial lateral head x-rays were taken at 1.5, 6, 12, and 18 weeks of age. Results revealed that by 1.5 weeks of age the congenital animal already exhibited changes in the cranial vault, cranial base, midface, and orthocephalic cranial base angles compared to controls. By 6 weeks of age, animals with experimental immobilization showed compensatory growth patterns similar to the congenital animal, particularly at the calvarial sutures and upper midface. This pattern continued through 18 weeks. Results showed that experimental, postnatal CS immobilization produced similar craniofacial growth patterns to those observed for our single congenital animal, but to a lesser degree, and therefore validates, in part, findings from experimental rabbit models of synostosis.

Congenital Bilateral Coronal Suture Synostosis in a Rabbit and Craniofacial Growth Comparisons with Experimental Models

Abstract Experimental rabbit models of postnatal coronal suture (CS) synostosis have helped make significant contributions towards the understanding and surgical management of human congenital craniosynostosis. The present study compares craniofacial growth patterns in animals with experimental CS immobilization and in a rabbit born in our laboratory with congenital CS synostosis. The study sample consisted of 10 sham controls, 14 experimental animals with bilateral CS immobilization, and one animal with congenital, bilateral CS synostosis. At 1.5 weeks of age, all animals had amalgam markers placed on either side of the frontonasal, coronal, and anterior lambdoid sutures. At this time, the experimental animals had bilateral CS immobilization using methyl-methacrylate. Serial lateral head x-rays were taken at 1.5, 6, 12, and 18 weeks of age. Results revealed that by 1.5 weeks of age the congenital animal already exhibited changes in the cranial vault, cranial base, midface, and orthocephalic cranial base ...

Frontal Bone Advancement and Compensatory Craniofacial Growth Changes in Rabbits with Experimental Coronal Suture Immobilization

Recent clinical advances in the surgical correction of coronal suture synostosis involve the overcorrection of a frontal bone segment to allow for unrestricted expansion of the developing neurocapsular matrix. However, the effects of such large-scale calvarial repositioning on subsequent brain mass growth trajectories and compensatory cranio-facial growth changes is unclear. This study was designed to investigate this relationship in an experimental rabbit model of bilateral coronal suture synostosis. Amalgam markers were placed across the frontonasal, coronal, and anterior lambdoid sutures in thirty-one 1.5-week-old rabbits. Twenty-one animals underwent bilateral coronal suture immobilization using methyl-methacrylate. Ten animals were left untreated and served as sham controls. At 6 weeks of age, the coronal suture was released by frontal bone craniotomy or frontal bone craniotomy with a 6-mm frontal bone advancement. Lateral head radiographs were taken at 1.5, 6, 7, 9, 12, and 18 weeks of age. Results revealed that by 6 weeks of age, animals with coronal suture immobilization exhibited growth disturbances across the various sutures resulting in altered craniofacial and cranial vault shape compared to control animals. Following coronal suture release, animals that underwent craniotomy showed rapid restenosis, which resulted in significantly altered cranial vault shape and cranial orthocephalization by 18 weeks of age. Animals that underwent frontal bone advancement exhibited normal overall craniofacial growth by 18 weeks of age compared with control animals but did exhibit regional compensatory growth disturbances at the frontonasal and anterior lambdoid sutures, possibly related to neural tissue distension.(ABSTRACT TRUNCATED AT 250 WORDS)