Search

Cranial synchondroses are cartilaginous joints between basicranial bones or between basicranial bones and septal cartilage, and have been implicated as having a potential active role in determining craniofacial form. However, few studies have examined them histologically. Using histological and immunohistochemical methods, we examined all basicranial joints in serial sagittal sections of newborn heads from nine genera of primates (five anthropoids, four strepsirrhines). Each synchondrosis was examined for characteristics of active growth centers, including a zonal distribution of proliferating and hypertrophic chondrocytes, as well as corresponding changes in matrix characteristics (i.e., density and organization of Type II collagen). Results reveal three midline and three bilateral synchondroses possess attributes of active growth centers in all species (sphenooccipital, intrasphenoidal, presphenoseptal). One midline synchondrosis (ethmoseptal) and one bilateral synchondrosis (alibasisphenoidal synchondrosis [ABS]) are active growth centers in some but not all newborn primates. ABS is oriented more anteriorly in monkeys compared to lemurs and bushbabies. The sphenoethmoidal synchondrosis (SES) varies at birth: in monkeys, it is a suture-like joint (i.e., fibrous tissue between the two bones); however, in strepsirrhines, the jugum sphenoidale is ossified while the mesethmoid remains cartilaginous. No species possesses an SES that has the organization of a growth plate. Overall, our findings demonstrate that only four midline synchondroses have the potential to actively affect basicranial angularity and facial orientation during the perinatal timeframe, while the SES of anthropoids essentially transitions toward a "suture-like" function, permitting passive growth postnatally. Loss of cartilaginous continuity at SES and reorientation of ABS distinguish monkeys from strepsirrhines., (© 2021 American Association for Anatomy.)

Timing of craniofacial suture fusion is important for the determination of demographics and primate ontogeny. There has been much work concerning the timing of fusion of calvarial sutures over the last century, but little comprehensive work focusing on facial sutures. Here we assess the relationships of facial suture fusion across ontogeny among select catarrhines. Fusion timing patterns for 5 facial sutures were examined in 1,599 crania of Homo, Pan, Gorilla, Pongo, Hylobatidae, Papio, and Macaca. Calvarial volume (early ontogeny) and dental eruption (late ontogeny) were used as indicators of stage of development. General linear models, test for homogeneity of slopes, and ANOVA were used to determine differences in timing of fusion by taxon. For calvarial volume, taxonomic groups segregated by regression slopes, with models for Homo indicating sutural fusion throughout ontogeny, Pongo, Macaca, and Papio representing earlier and more complete suture fusion, and Pan, Gorilla, and Hylobatidae indicating very early facial suture fusion. Similar patterns are observed when dental eruption is used for developmental staging. Only Gorilla and Hylobatidae are observed to, generally, fuse all facial suture sites in adulthood. Finally, Homo appears to be unique in its delay and patency of sutures into late ontogeny. The taxonomic patterns of facial suture closure identified in this study likely reflect important evolutionary shifts in facial growth and development in catarrhines., (© 2021 S. Karger AG, Basel.)

Objectives: Craniosynostosis affects 1 in 2000 to 3000 live births and may result in craniofacial and neural growth disturbances. Histological data have shown that thick collagenous bundles are present in the sutural ligament, which may tether the osteogenic fronts, resulting in premature fusion. The hormone relaxin has been shown to disrupt collagen fiber organization, possibly preventing craniosynostosis by relaxing the sutural ligament and allowing osteogenic fronts to separate normally and stay patent. This study tested this hypothesis with a rabbit model of delayed-onset coronal suture synostosis., Methods: A total of 18 New Zealand White rabbits with craniosynostosis were randomly assigned to one of three groups: sham control, protein control (BSA), relaxin treatment. After initial diagnosis, sham surgery, BSA, or relaxin was delivered to the fusing coronal suture in a slow-release (56-day) collagen vehicle. Longitudinal radiographs and body weights were collected at 10, 25, 42, and 84 days of age, and sutures were harvested for histology., Results: Relaxin-treated animals had more disorganized intrasuture content than control groups. These specimens also appeared to have relatively wider sutures ectocranially. There were no significant differences in relaxin-treated animals for all craniofacial growth measures, or suture separation compared with controls., Conclusions: These data do not support our initial hypothesis that the use of relaxin may rescue sutures destined to undergo premature suture fusion. These findings suggest that collagen fiber arrangement may not be important for suture fusion. This protein therapy would not be clinically useful for craniosynostosis.

Background: Craniosynostosis is defined as the premature fusion of one or more cranial sutures. Bone morphogenetic proteins (BMPs), regulators of ossification, have been implicated in premature suture fusion. Noggin, an extracellular BMP inhibitor, has been shown experimentally to inhibit resynostosis following surgery. The present study was designed to test the hypothesis that BMP inhibition using noggin therapy may rescue sutures destined to fuse by inhibiting initial ossification., Methods: Twenty-six, 10-day old rabbits with familial, delayed-onset, coronal suture synostosis were randomly divided into three groups: (1) the sham surgical control group, (2) the bovine serum albumin-treated group [10 μg/suture (protein/vehicle controls)], and (3) the noggin therapy group (10 μg/suture; experimental group). Sutural growth was monitored by radiopaque markers implanted at 10 days of age. At 25 days, the bovine serum albumin or noggin was combined with a slow-resorbing collagen vehicle and injected subperiosteally above the coronal suture. Somatic and sutural growth data were collected at 10, 25, 42, and 84 days of age. Coronal sutures were harvested at 84 days to histologically assess fusion., Results: Results showed no significant (p > 0.05) differences in suture separation at any age. Suture fusion assessed by histomorphology did not differ among the three groups. Although previous data showed noggin to inhibit postoperative resynostosis in this craniosynostotic rabbit model, here there was no effect on initial suture fusion., Conclusion: These results suggest that in this rabbit model of craniosynostosis, BMPs do not play a role in the pathogenesis of craniosynostosis and only play a role in postoperative bony wound healing.

Research has implicated the faulty regulation of transforming growth factor beta signaling as one mechanism for premature calvaria suture fusion. Androgens have been shown to increase the expression and activity of the transforming growth factor beta, resulting in increased osteoblast proliferation and differentiation and possibly premature suture fusion. The present study was designed to test the hypothesis that flutamide, an androgen receptor-blocking agent, would "rescue" a coronal suture destined to fuse and improve craniofacial growth in a familial rabbit model of craniosynostosis. Thirty rabbits with delayed-onset, coronal suture synostosis were examined via longitudinal cephalometry. The rabbits were divided into 4 groups: (1) sham surgical controls (n = 10), (2) bovine serum albumin (500 ng) protein controls (n = 6), (3) flutamide diluent controls (n = 6), and (4) flutamide (15 mg dissolved in ethanol) experimental group (n = 8). At 10 days of age, radiopaque amalgam markers were implanted in all rabbits on either side of the coronal suture to monitor sutural growth. At 25 days of age, the bovine serum albumin, ethanol, and flutamide were combined with a slow-resorbing collagen vehicle and injected subperiosteally above the coronal suture into the respective groups. Although results revealed a slight but significant increase in coronal suture marker separation in flutamide-treated rabbits compared with controls at 42 days of age, few significant differences were noted for craniofacial growth and intracranial volume among groups. Results suggest that androgen receptor-blocking using flutamide may only provide a transient rescue to suture fusion in this model. Further research is needed to investigate the effects of hormones on suture development and maintenance.

In addition to acting as a growth site, sutures in the facial skeleton are important for distributing mechanical forces during mastication. In the present study, the extent of fusion of a facial suture is assessed in two samples of adult bushbabies (Galago moholi and Otolemur garnettii). Microanatomical techniques were used to determine the loci of osseous bridges across the nasomaxillary suture (NMS). Histological sections containing sutures with osseous bridging were rated as "fused." One of the specimens was studied using micro-computed tomography before paraffin embedding and serial sectioning. At all ages, O. garnettii shows more advanced fusion of the NMS than G. moholi. The youngest O. garnettii shows multiple foci of fusion of the NMS; however, 13% of the posterior most suture is patent. Throughout the NMS of this animal, sutural fusion is isolated to one or two small osseous bridges, typically of woven bone. These bridges are most often on the external (superficial) surface of the suture, but in numerous sections the site of fusion occurs deep to an external notch. In G. moholi, the youngest adults studied showed little or no fusion across the NMS. However, the nasal and maxillary bones were indirectly tethered at some levels by other bones that were fused to both nasal and maxillary bones. These results indicate that microanatomical evidence is required to fully assess the extent of fusion of facial sutures. These findings also support previous observations of differing magnitude of suture fusion between the two species., ((c) 2010 Wiley-Liss, Inc.)

The extent of fusion in facial sutures has implications for topics ranging from biomechanics to phylogeny reconstruction. An unfortunate limitation of studying sutural fusion in skeletal specimens is that it is difficult to assess whether apparently patent sutures are in fact fused internally. Both histology and microcomputed tomography (CT) are potential tools for solving this, but relatively few studies have attempted to discern the limits of micro CT for visualization of microanatomical structures. We examined microanatomical aspects of facial sutures in adult cadaveric samples from captive bushbabies. Premaxillary and nasopremaxillary sutures were examined in serially sectioned snouts of four greater bushbabies (Otolemur garnettii) and four lesser bushbabies (Galago moholi). Sections containing sutures with osseous bridging were rated as "fused," and the presence or absence of grooves on the external side was recorded. One bushbaby was studied using micro CT prior to physical sectioning. O. garnettii and two of the G. moholi show multiple foci of fusion. Histological examination confirmed that sutural fusion is limited to the internal surface in numerous sections, resulting in an external notch. Such points of internal fusion could be clearly visualized in raw CT slices. The presence of such notches suggests that external examination can underestimate the degree of suture fusion. Thus, microanatomical evidence may be needed to fully assess biomechanical correlates and phylogenetic interpretations based on fusion of facial sutures. Our results also indicate micro CT may be a useful tool to obtain this evidence.

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 sinuses was also assessed. Impressions of the middle meningeal vessels were assessed for depth, width, and degree of convolution. For width of the dural venous sinuses and area of the confluens of sinuses, comparisons among groups were made with a one-way analysis of variance (ANOVA). For depth of the dural venous sinuses and impressions of the middle meningeal vessels, comparisons among groups were made using a Kruskal-Wallis one-way ANOVA., Results: Crania with familial coronal suture synostosis had significantly (p <.05) reduced posterior dural venous sinus dimensions when compared with both crania from rabbits with experimental immobilization of the coronal suture and rabbits with normal coronal sutures. Crania with both coronal suture synostosis and experimental immobilization had significant increases in dimensions of the middle meningeal vessels relative to normal crania. In addition, casts from rabbits with unicoronal suture synostosis showed marked asymmetry in the dural venous sinuses., Conclusions: These results support the hypothesis that craniosynostosis is associated with alterations in endocranial vasculature. These changes are most likely a secondary response to synostosis rather than a causal factor and may reflect increased intracranial pressure, decreased intracranial volume, and local accumulations and reductions of cerebrospinal fluid in the posterior region of the skull and immediately deep to the coronal suture.

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 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: 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., Conclusions: 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.

Previous studies from our laboratory have characterized the craniofacial morphology and growth patterns of an inbred strain of rabbits with autosomal dominant coronal suture synostosis. A number of rabbit perinates from this colony have been collected sporadically over a 5-year period with premature interfrontal suture synostosis. The present study describes the very early onset of craniofacial dysmorphology of these rabbits and compares them to similar-aged normal control rabbits. A total of 40 perinatal New Zealand White rabbits were used in the present study. Twenty-one comprised the sample with interfrontal suture synostosis and ranged in age from 27 to 38 days postconception (term = 31 days) with a mean age of 33.53 days (+/-2.84 days). Nineteen rabbits served as age-matched, normal controls (mean age = 33.05 days +/-2.79 days). Lateral and dorsoventral radiographs were collected from each rabbit. The radiographs were traced, computer digitized, and 12 craniofacial measurements, angles, and indices were obtained. Mean measures were compared using an unpaired Student's t-test. All synostosed rabbits were stillborn or died shortly after birth. Grossly, these rabbits exhibited extreme frontal bossing, trigonocephaly with sagittal keeling, and midfacial shortening. No somatic anomalies were noted. Radiographically, rabbits with interfrontal suture synostosis had significantly (P < 0.05) narrower bifrontal widths, shorter cranial vault lengths, kyphotic cranial base angles, and different cranial vault indices (shapes) compared to controls. Results reveal severe and early pathological and compensatory cranial vault changes associated with premature interfrontal suture synostosis in this rabbit model. The 100% mortality rate noted in this condition may be related to the inheritance of a lethal genetic mutation or to neural compression from reduced intracranial volume. Results are discussed in light of current pathogenic hypotheses for human infants with premature metopic suture synostosis., (Copyright 2000 Wiley-Liss, Inc.)

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 three groups by approximately 146%. However, by 42 days of age, mean ICP in normal control rabbits and rabbits with DOCS was significantly (p < .01) increased compared with their mean ICP values seen at 25 days of age, while mean ICP in BCS rabbits significantly (p < .01) decreased (by 32%) over the same time period. ICP in rabbits with UCS was between that seen in normal control rabbits and rabbits with BCS and did not significantly (p > .05) change over time., Conclusions: These findings suggest that the degree of suture involvement may be related to early increases in ICP. Possible multifactorial explanations for intracranial decompression and compensation in the craniosynostotic rabbit model are discussed.

Objective: Simple craniosynostoses produce predictable morphologies of the cranial vault, with growth deficits in a direction parallel to the synostosed suture and compensatory growth at sutures that are perpendicular to and attached to the synostosed one. In coronal suture synostosis, anteroposterior growth is inhibited, with compensatory growth in a transverse direction. Information on growth patterns and influence on other craniofacial regions are not as clear. This study tested the hypotheses that (1), both juvenile and adult rabbits with familial, nonsyndromic coronal suture synostosis exhibit significant size and shape differences of the entire craniofacial region relative to normal rabbits as a result of altered growth patterns and that (2), shape differences of the calvaria will precede those of the basicranium., Design: Fifty anatomic landmarks were located on 94 New Zealand white rabbit crania. The crania were divided into a juvenile, six-week-old age category (n = 53) and an adult, 18-week-old category (n = 41) in order to assess shape differences at different ages. Each age category was sorted into three groups based on growth at the coronal suture: normal sutural growth, delayed onset synostosis, and complete synostosis. Landmarks were digitized in three-dimensions, and statistical analyses on shape differences were carried out using Euclidean distance matrix analysis (EDMA)., Results and Conclusions: Results showed that delayed onset synostosis did not produce craniofacial morphology that was different from normal at any age. However, complete synostosis yielded predictable and global craniofacial shape differences at both ages relative to normal skulls, producing an overall shorter, wider cranium with the most markedly compensating regions in a posterosuperior position of the skull. In addition, delayed onset synostosed crania showed no shape differences in the basicranium, relative to normal crania, suggesting primacy of the calvaria in this model of coronal synostosis. However, further investigations are necessary to verify primacy of the calvaria in this model.

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.

Recent studies have identified a subpopulation of persons with craniosynostosis who exhibit progressive or delayed-onset synostosis and mild cranial vault deformities. These persons may be good candidates for nonextirpation distraction osteogenesis. The present studies were designed to determine force-displacement parameters and assess the effects of distraction osteogenesis on coronal suture growth and morphologic characteristics in a rabbit model with congenital, delayed-onset craniosynostosis. Data were collected from a total of 178 rabbits: 71 normal controls; 16 normal controls with distraction; 72 with delayed-onset coronal suture synostosis; and 19 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the coronal suture. In the force-displacement study, force-displacement distractors were placed across the coronal suture and distracted acutely for 1.0 mm at 42 days of age. Force-displacement curves for the coronal suture were best described by a third-order polynomial regression equation for both normal and synostosed groups. Significant differences (P < 0.05) were found in the mean force necessary to distract a normal suture 1 mm in distance (13.72 kg) compared with a suture with delayed-onset synostosis (48.39 kg). A significant (P < 0.05) relationship was also found between the extent of synostosis and the distractive force in rabbits with delayed-onset synostosis. In the distraction study, internal distractors were fixed across the coronal suture at 25 days of age and percutaneously and intermittently activated at an average of 0.11 mm/day for 42 days (4.54 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis and distraction had significantly (P < 0.01) more coronal suture growth rates compared with rabbits with delayed-onset synostosis and no distraction. Coronal sutures were harvested at 84 days of age for qualitative histologic examination. Normal, distracted coronal sutures showed widened sutural ligaments and thin, active osteogenic fronts. In contrast, distracted coronal sutures from rabbits with delayed-onset synostosis showed narrowed sutural ligaments, thickened and blunt osteogenic fronts, and increased collagen and bony matrix deposition compared with controls. Results suggest that distraction osteogenesis without corticotomy may be a treatment alternative in persons with progressive, delayed-onset synostosis. However, these preliminary data also suggest that distractive forces may accelerate or stimulate osteogenesis differentially in persons with craniosynostosis, possibly through an underlying genetic disorder of bone and cytokine regulation. These differential osteogenic responses to distraction, if validated clinically, will need to be taken into account when planning distraction rate and rhythm protocols for patients with craniosynostosis.

Recent studies have identified a subpopulation of craniosynostotic individuals who exhibit progressive or delayed-onset synostosis and mild craniofacial growth abnormalities. These individuals may be good candidates for nonextirpation, distraction osteogenesis therapy. The present study was designed to test this hypothesis by using internal calvarial bone distraction in a rabbit model with familial delayed-onset craniosynostosis. Data were collected from 159 rabbits: 71 normal controls, 72 with delayed-onset coronal suture synostosis, 8 with delayed-onset coronal suture synostosis and coronal suturectomy, and 8 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the frontonasal, coronal, and anterior lambdoidal sutures. At 25 days of age, correction was accomplished through either a 5-mm-wide suturectomy or distraction osteogenesis. An internal distraction appliance was fixed to the frontal and parietal bones and percutaneously and intermittently activated at an average of 0.10 mm/day for 42 days (4.11 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis had significantly (p < 0.01) reduced coronal suture growth rates (0.04 mm/day) compared with the other three groups (0.07 mm/day). Rabbits with suturectomy and rabbits with distraction showed similar coronal suture responses. However, from 42 to 84 days of age, rabbits with distraction showed reduced growth at the vault sutures and abnormal growth patterns in cranial vault width, cranial vault shape, and cranial base angulation compared with the other three groups. Results demonstrated that, although the normal coronal suture growth rate was maintained in rabbits with delayed-onset synostosis using intermittent distraction osteogenesis, normal adult craniofacial structure was not achieved. Such anomalous growth was probably a result of altered growth vectors and compressive forces at adjacent sutures during distraction. These findings suggest that distraction osteogenesis without corticotomy may be a treatment alternative in individuals with progressive, delayed-onset synostosis, but that internal appliances that generate low-level, continuous distractive forces should be investigated and developed.

This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis, and this second part presents neuropathological findings and age-related changes in intracranial volume (ICV) and intracranial pressure (ICP) in 106 normal rabbits and 56 craniosynostotic rabbits from this colony. Brain morphology and anteroposterior length were described in 44 rabbit fetuses and perinates (27 normal; 17 synostosed). Middle meningeal artery patterns were qualitatively assessed from 2-D PCC MRI VENC scans and endocranial tracings from 15, 126-day-old rabbits (8 normal, 7 rabbits with unicoronal synostosis). Brain metabolism was evaluated by assessing 18F-FDG uptake with high-resolution PET scanning in 7, 25-day-old rabbits (3 normal, 4 with unicoronal or bicoronal synostosis). Intracranial contents and ICV were assessed using 3-D CT scanning of the skulls of 30 rabbits (20 normal,10 with unicoronal synostosis) at 42 and 126 days of age. Serial ICP data were collected from 66 rabbits (49 normal; 17 with unicoronal synostosis) at 25 and 42 days of age. ICP was assessed in the epidural space using a Codman NeuroMonitor microsensor transducer. Results revealed that cerebral cortex morphology was similar between normal and synostosed fetuses around the time of synostosis. Significantly (P<0.05) decreased A-P cerebral hemisphere growth rates and asymmetrical cortical remodeling were noted with increasing age in synostotic rabbits. In addition, rabbits with unicoronal suture synostosis exhibited asymmetrical middle meningeal artery patterns, decreased and asymmetrical brain metabolism, a "beaten-copper" intracranial appearance, significantly (P<0.05) decreased ICV, and significantly (P<0.01) elevated ICP compared with normal control rabbits. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent clinical neuropathological, ICV, and ICP findings recorded in human craniosynostotic studies.

Poswillo has stated, "The more severe anomalies of the calvaria, such as plagiocephaly, Crouzon [syndrome], and Apert syndrome still defy explanation, in the absence of an appropriate animal system to study" (p. 207). This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis. Part 1 presents pathological findings and compensatory sutural growth data from 109 normal rabbits and 82 craniosynostotic rabbits from this colony. Synostotic foci, onset, and progression were described in the calvariae from 102 staged (fetal days 21, 25, 27, 33; term = 30 days) fetuses (39 normal, 63 synostosed). Calvarial suture growth patterns from 10 to 126 days of age were assessed from serial radiographs obtained from 89 rabbits (70 normal rabbits and 19 rabbits with unicoronal suture synostosis) with amalgam bone marker implants. Perinatal results revealed that by fetal day 25 the synostotic focal point in synostotic rabbits consistently originated from the endocortical surface of the calvaria in the middle of the coronal suture at a presumed high-tension, interdigitating zone. Histological analysis revealed hyperostotic osteogenic fronts on the affected side compared with the unaffected side. Postnatal sutural growth data revealed a predictable pattern of plagiocephaly (contralateral coronal sutures growing more than ipsilateral sutures and ipsilateral frontonasal and anterior lambdoidal sutures growing more than contralateral sutures), which resulted in early cranial vault deformities and a double "S" shape torquing towards the affected side. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent cytokine and genetic findings from human craniosynostotic studies.