Craniofacial dyssynostosis in two boys with apparently normal cognitive development.
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Child, Preschool↗
Biomedical subjects
Steven R Buchman
Publications and source records attributed to Steven R Buchman.
Extracellular signal-related kinase and bone morphogenetic protein expression during distraction osteogenesis of the mandible: in vivo evidence of a mechanotransduction mechanism for differentiation and osteogenesis by mesenchymal precursor cells.
BACKGROUND: The goal in this study was to investigate the role of extracellular signal-related kinase (ERK) 1/2, a central regulator of mesenchymal stem cell differentiation, and its temporal relationship to bone morphogenetic protein (BMP) 2/4, a potent osteogenic growth factor, during live model distraction osteogenesis. METHODS: The authors examined histomorphometric expression through the early temporal sequence for both ERK 1/2 and BMP 2/4 during gradual distraction to 5.1 mm (n = 12 net). Comparison groups (group sizes, n = 12) included an acute critical-size defect of 5.1 mm and a subcritical-size defect of 2.1 mm. RESULTS: In the group gradually distracted to 5.1 mm, immunohistochemical analysis demonstrated significant intranuclear expression of ERK 1/2 within mesenchymal precursor cells at the osteotomy edges early in distraction (postoperative days 6 and 9). ERK 1/2 became increasingly localized to hypertrophic chondrocytes within the distraction regenerate during the later stages of distraction (postoperative day 16). Adjacent sections examined for BMP 2/4 expression established a close temporal and spatial correlation with ERK 1/2. BMP 2/4 expression was initially present in the regions surrounding mesenchymal precursor cells expressing ERK 1/2, but then developed most prominently within the cytoplasm of hypertrophic chondrocytes expressing ERK 1/2 late in distraction. Comparison groups consistently demonstrated either fibrous nonunion or bony union typical in fracture healing, depending on defect size. However, even specimens with subcritical-size defects and complete bony union were consistently found to have minimal ERK 1/2 expression. CONCLUSIONS: These data provide evidence that ERK 1/2 expression is present within mesenchymal precursor cells during distraction osteogenesis and that ERK expression correlates closely with BMP 2/4 expression. The presence of ERK 1/2 expression only during gradual distraction strongly implicates the concept that mechanical strain appears to be the key upregulating factor for ERK 1/2 expression, based on comparison with fracture-healing and critical-size defect specimens.
Animals↗
Social response in children with severe cognitive impairments: factors in craniofacial surgery decision-making.
BACKGROUND: The controversy over whether certain pediatric craniofacial operations primarily address "functional" versus "aesthetic" goals has fostered tensions among insurance companies, patients and families, and treatment teams. The authors posit that such operations have objectives and outcomes that can be categorized as "functionally aesthetic" and describe the empirical basis for this assertion. Furthermore, the authors apply this concept to the difficult surgical decision-making process associated with treating children with severe cognitive impairments. METHODS: When patients have severe cognitive impairments, the social benefits of treatment may be less clear than for other patients, increasing the complexity of surgery decision-making. The authors discuss the nature of cognitive impairment, its prevalence in patients with craniofacial anomalies, links between social functioning and both cognitive development and appearance, and the importance of social integration for psychological and cognitive functioning. Special issues involved in working with cognitively impaired children are covered, including parent and patient expectations for surgical outcome and the difficulties involved in pain assessment and control. Potential linkages are described for craniofacial surgery, appearance, social functioning, and cognitive development. CONCLUSIONS: A craniofacial operation directed at reconstruction of a congenital defect in a child should not be dismissed as simply and purely cosmetic. The authors document and outline the potential ethical issues and social and cognitive benefits that should be considered by insurance companies, patients and families, and treatment teams when determining treatment options for cognitively impaired children with craniofacial anomalies.
Child↗
Colocalization of c-Src (pp60src) and bone morphogenetic protein 2/4 expression during mandibular distraction osteogenesis: in vivo evidence of their role within an integrin-mediated mechanotransduction pathway.
Craniofacial distraction osteogenesis (DO) is an evolving reconstructive technique with expanding applications for the treatment of bony deficiencies of the facial skeleton. Mechanical force has been known to play a fundamental role in modulating sustained osteogenic response and therefore is believed to function as a critical regulator of DO. We hypothesize that key clustering components of an integrin-mediated signaling pathway, including c-Src (pp60), are necessary for mediating the response to mechanical force. The specific aim of this study is to demonstrate up-regulation of a key focal adhesion molecule, c-Src, selectively in new bone formation subject to the mechanical forces of distraction and to demonstrate a lack of that same up-regulation in new bone formation associated with simple fracture healing. An additional specific aim is to demonstrate colocalization of c-Src expression and bone morphogenetic protein (BMP 2/4) expression during mandibular DO. Using a rat model of mandibular DO, c-Src and BMP 2/4 expression were evaluated in critical size defects, subcritical size defects, and mandibles undergoing gradual distraction. Osseous regeneration was observed in the course of gradual distraction; this process was associated with increased expression of c-Src. Furthermore, the presence of BMP 2/4 closely approximated c-Src expression spatially and temporally, suggesting a link between cytoplasmic focal adhesion activation and the resultant nuclear regulation of osteogenic protein expression. In significant contradistinction, minimal c-Src expression was found in the subcritical-sized defects where the fractures healed secondarily but where no gradual distraction was performed. Instead, the new bone formation inherent in the secondarily healed subcritical-sized defects demonstrated expected BMP 2/4 expression but was devoid of an up-regulation of c-Src. Finally, as expected, minimal expression of both c-Src and BMP was found in fibrous nonunion specimens. C-src expression was observed during gradual distraction; furthermore, minimal c-Src expression was visualized during subacute and critical-size defect fracture healing. C-Src expression also closely approximated BMP expression during DO. These findings that c-Src expression is found primarily only during conditions of cyclic distraction forces strongly implicates that mechanical force during gradual distraction is associated with c-Src expression. These results provide in vivo support for previous in vitro evidence that mechanical force profoundly influences osseous regeneration during distraction osteogenesis by means of a c-Src dependent mechanotransduction pathway, resulting in increased expression of osteogenic proteins, including BMP 2/4.
Animals↗
Progressive postnatal craniosynostosis and increased intracranial pressure.
Since its first description by Virchow in 1851, craniosynostosis has been known as a potentially serious condition resulting in premature fusion of skull sutures. Traditionally, craniosynostosis has been regarded as an event that occurs early in fetal development, resulting in a skull shape at birth that is determined by the suture or sutures involved. In recent years, a different form of craniosynostosis has been observed. Patients initially come to the attention of physicians because they exhibit midface hypoplasia or occasionally hypertelorism. The affected individuals all have a normal skull shape and open sutures in infancy but develop multiple-suture craniosynostosis postnatally, ultimately requiring surgical correction. These cases are significant because, although the patients do not initially display the physical manifestations of craniosynostosis, they frequently develop increased intracranial pressure, which can have devastating consequences. Unless these patients are recognized and vigilant follow-up monitoring is instituted at an early age, permanent impairment can result. A retrospective chart review study was conducted, and patients with multiple-suture craniosynostosis who developed symptoms of increased intracranial pressure were selected. The patients were divided into two groups, namely, those with normal sutures and/or head shape at birth (progressive craniosynostosis) (n = 15) and those with abnormal head shapes at birth (classic syndromic craniosynostosis) (n = 12). Clinical and radiological findings typically used to monitor the development of increased intracranial pressure were reviewed for both groups and compared. In addition, mutational analyses were performed. All patients with progressive postnatal craniosynostosis demonstrated clinical, radiological, or ophthalmological evidence of increased intracranial pressure, requiring skull expansion. Those patients displayed papilledema, anterior fontanelle bulge, and thumbprinting more often than did the patients with classic craniosynostosis. Thirteen of 15 patients were given the clinical diagnosis of Crouzon syndrome, which raises the question of whether such patients represent a subset of patients with this syndrome. Mutational analyses for the patients with progressive craniosynostosis demonstrated that, of 13 patients tested, 11 had mutations in exon 7 or 9 of FGFR2, which is a common site of mutations in Crouzon syndrome. The traditional indications of increased intracranial pressure used to monitor patients with classic craniosynostosis can be used to monitor patients with progressive postnatal craniosynostosis, particularly anterior fontanelle bulge, papilledema, and thumbprinting. It is thought that regular monitoring of these characteristics may lead to earlier diagnosis and allow for surgical intervention before the development of undesirable outcomes. It is important for clinicians to be aware of this group of patients, because any delay in diagnosis and treatment can result in severe consequences for the patients.
Child↗
Conservative management of large avulsions of the lip and local landmarks.
Large lip avulsion injuries that involve significant tissue loss to the lip vermilion and other local landmarks can often pose a surgical dilemma for the reconstructive surgeon. Immediate reconstruction of these injuries are frequently performed using local flaps and adjacent tissue transfer to close the defect, but these repairs frequently suffer from the unfortunate consequence of increased associated scarring and further permanent distortion of the local anatomy. We present 2 patients sustaining dog bite injuries associated with extensive traumatic tissue loss to the lip vermilion and other local landmarks. These patients were treated conservatively with excellent functional and cosmetic results. A single minor surgical revision of 1 patient's cupid's bow was performed 1 year after injury. In cases of significant traumatic avulsion involving the lip vermilion and the perioral composite soft tissue, even with injuries including delicate anatomic landmarks, healing by secondary intention can be instituted as the initial treatment of choice in younger patients, often providing optimal results.
Administration, Topical↗
Pediatric mandibular distraction osteogenesis: the present and the future.
Pediatric mandibular distraction osteogenesis (MDO) has become a mainstay of treatment for patients with micrognathia and retrognathia. As craniofacial surgeons have gained experience with MDO, the technique has become a safe and durable means of mandibular lengthening that avoids the significant morbidity of conventional surgical treatments. The full impact of this technique has not yet been realized for pediatric patients. Although studies have confirmed durable reconstruction of mandibular length with MDO, the range of applications of this technique is currently limited. As innovative clinicians continue to apply MDO to pediatric clinical craniofacial problems not easily treated with conventional means, the field of MDO will continue to mature. This article discusses current uses and examples of potential future applications of pediatric MDO. The development of novel and creative applications of MDO will advance the management of complex craniofacial anomalies, taking the field of craniofacial surgery into the future.
Child, Preschool↗
Focal adhesion kinase expression during mandibular distraction osteogenesis: evidence for mechanotransduction.
Distraction osteogenesis is an established treatment strategy in the reconstruction of the craniofacial skeleton. The underlying mechanisms that drive bone formation during this process are largely unknown, but a regulatory role for mechanical force is believed to be critical. The integrin-mediated signal transduction cascade is a primary pathway by which signal transduction of mechanical stimuli (i.e., mechanotransduction) occurs. Focal adhesion kinase (FAK) is a significant regulator in this pathway. The authors hypothesize that mechanical forces created during distraction osteogenesis are responsible for the osteogenic response that takes place, and that these changes arise through integrin-dependent mechanotransduction. Using a rat model of distraction osteogenesis, the authors examined the expression of FAK in critical size defects (n = 15), subcritical size defects (n = 15), and mandibles undergoing distraction osteogenesis (n = 15). Their findings demonstrated FAK immunolocalization in mandibles undergoing distraction osteogenesis, but not in the critical size defects or in subcritical size defects, despite varying degrees of bone formation in the latter two groups. Furthermore, bone sialoprotein mRNA in situ hybridization patterns were found to mirror FAK immunolocalization patterns in mandibles undergoing distraction osteogenesis, demonstrating an association of FAK expression with the osteogenic process specific to distraction osteogenesis. These findings suggest that the bone formation in distraction osteogenesis is regulated by mechanical force by means of integrin-dependent mechanotransduction pathways.
Animals↗
Volume maintenance of inlay bone grafts in the craniofacial skeleton.
Although the clinical use of inlay bone grafts is widespread in craniofacial surgery, the dynamics of inlay bone grafting to the craniofacial skeleton have never been well characterized. Previous work demonstrated that volume maintenance of bone grafts in the onlay position is a consequence of their microarchitectural features, rather than their embryological origins. The purpose of this study was to investigate whether the properties determining the volume maintenance of bone grafts in the onlay position in the craniofacial skeleton could be extended to bone grafts in the inlay position. It was hypothesized that volume maintenance of an inlay bone graft could be better explained on the basis of the microarchitectural features of the graft (cortical versus cancellous composition), rather than its embryological origin (membranous versus endochondral), and that the primary determinant of bone graft behavior is the interaction between the microarchitectural features of the bone graft and the local mechanical environment in which the bone graft is placed. Cortical and cancellous bone grafts were harvested from the iliac crest (endochondral origin) of 25 New Zealand white rabbits, and cortical bone was harvested from the mandible (membranous origin) of each rabbit. Four 7-mm trephine holes were made in the cranium of each rabbit, posterior to the coronal suture. Each defect was filled with endochondral cortical bone, endochondral cancellous bone, or membranous cortical bone or was left as an ungrafted control specimen. Animals were killed at 3, 8, or 16 weeks. Crania were subjected to micro-computed tomographic and histological assessments. Micro-computed tomographic analysis demonstrated significant increases in actual bone volume from time 0 to the time of death for all types of grafts. Cortical bone demonstrated significant increases in space-occupying volume at all time points. By 16 weeks, no statistically significant difference in either the actual bone volume or the space-occupying volume according to graft type could be detected. There was no resorption of the inlay bone grafts; in fact, all bone types exhibited increased volume. Cancellous bone demonstrated the greatest capacity to increase actual bone volume. All bone graft types seemed to reach a steady-state bone volume, as if controlled by a local regulator. The regulator is likely the local mechanical environment in which the grafts were placed, as corroborated by the findings that the bone grafts seemed to recapitulate the characteristics of the bone in which they were placed, rather than maintaining their native characteristics.
Animals↗
Efficacy of aprotinin in children undergoing craniofacial surgery.
OBJECT: This prospective, randomized, placebo-controlled, double-blind trial was undertaken to assess the efficacy of aprotinin in reducing the need for blood transfusions in 39 children undergoing reconstructive craniofacial surgery. METHODS: Two demographically similar groups--a total of 39 patients with a mean age of 1.2 +/- 1.2 years--were studied. The efficacy of aprotinin (240 mg/m2 administered intravenously over 20 minutes, followed by infusions of 56 mg/m2/hr) was compared with that of an equal infusion of 0.9% saline (placebo). Patients in the aprotinin group received less blood per kilogram of body weight than patients in the placebo group (32 +/- 25 ml/kg compared with 52 +/- 34 m/kg, respectively; p = 0.04). Those patients in whom aprotinin was administered experienced less change in their hematocrit levels during surgery (aprotinin -33 +/- 13% compared with placebo -44 +/- 9%, p = 0.01). Each patient underwent a transfusion as per study protocol, and there was no significant change in hematocrit levels from the beginning to the end of surgery. The surgical faculty judged blood loss in patients in the aprotinin group to be significantly less than usual (p = 0.03). The use of aprotinin was also associated with reduced blood transfusion requirements during the first 3 postoperative days (p = 0.03). There was no adverse event reported in either the aprotinin or placebo group. CONCLUSIONS: Aprotinin decreased blood transfusion requirements in pediatric patients undergoing craniofacial reconstruction, thereby reducing the risks associated with exposure to banked blood components.
Algorithms↗
Frontoorbital reconstruction.
The care of the patient with craniosynostosis is perhaps the most challenging problem in craniofacial surgery. The syndromes vary in their presentation and severity; however, many of the structural and functional sequelae have common characteristics. The multifaceted medical problems of these children are particularly well suited to a multidisciplinary team approach to their care. The surgeons must be aware of the most pressing health concerns of these patients and incorporate those concerns into a well-formulated phased plan of comprehensive reconstruction. The overall goals of treatment of syndromic and nonsyndromic craniosynostosis continually should guide the care of these exceptional children. Those goals are to provide a predictable and durable reconstruction that restores facial form, reestablishes symmetry, attains the best results in the least number of operations, and infuses the patient with a sense of emotional and physical health.
Brain↗
Unique rodent model of distraction osteogenesis of the mandible.
Despite the increasing use of distraction osteogenesis (DO) of the mandible, the molecular mechanisms regulating new bone formation during DO remain poorly understood. The purposes of this study were (1) to establish a unique rodent model of DO capable of outlining parameters for new bone formation at the distraction site and (2) to determine a critical-size defect to differentiate osteogenesis resulting from distraction from conventional fracture healing at the osteotomy site. Adult Sprague-Dawley rats were fitted successfully with this newly developed distraction device. Analyses demonstrated that the device could distract the rat mandible reliably to 5.1 mm with complete union. Acute intersegmental gaps of 2 mm resulted in complete bony union in a manner consistent with fracture healing, whereas 3-mm acute gaps resulted in varying degrees of bony union. Acute intersegmental gaps of 5.1 mm invariably resulted in fibrous nonunion. In summary, the authors have developed a rodent model of DO of the mandible. Their distraction protocols resulted successfully in advancement to 5.1 mm with bony consolidation. Notable fracture healing occurred at immediate intersegmental spaces as large as 3 mm. A gap of 5.1 mm was sufficient to act as a critical-size defect, resulting consistently in fibrous nonunion. These findings validate the effectiveness of this distraction device and establish the critical-size defect of a rat mandible at more than 3 mm. This novel model of DO provides an effective method of examining fundamental mechanisms responsible for new bone formation in the craniofacial skeleton.
Animals↗
Complete osseous regeneration of a large skull defect in a patient with cutis aplasia: a conservative approach.
Cutis aplasia (or aplasia cutis congenita) is a congenital absence of all skin layers, often extending through bone. This defect usually occurs in the scalp and can be extensive, exposing the dura mater, and deeper meninges. Treatment regimens for cutis aplasia have included early operative intervention, including skin and bone grafts, local scalp flaps, or free flaps to close the defect. In addition to the significant perioperative risks, these invasive procedures may inhibit the osteogenic potential of the dura to initiate and sustain bony closure of the defect. We report a case of an infant with Adams-Oliver syndrome and cutis aplasia involving a large portion of the skull that was treated conservatively with topical Silvadene dressings. No surgical treatment of bone or soft tissue reconstruction was necessary. This case report is the first to our knowledge to document complete bony restoration of the cranial vault through serial three-dimensional CT scans. The intensive therapeutic intervention in this case report allowed early discharge from the hospital, a gradual amelioration of the patient's alopecia as the hair-bearing scalp slowly covered the defect, and precluded the need for any subsequent bony reconstruction of the cranial vault. We hypothesize that conservative treatment of cutis aplasia maintains dural induction of osseous regeneration, and any treatment plan for bony defects of cutis aplasia should consider maintenance of dural integrity. Although further investigation is warranted, an initial trial of antimicrobial dressing care might optimally promote secondary closure of the cranial vault without the need for surgical intervention.
Administration, Cutaneous↗
Mandibular distraction in the absence of an ascending ramus and condyle.
The introduction of distraction osteogenesis (DO) as a method of mandibular elongation has provided the craniofacial surgeon with a valuable tool in the approach to patients with mandibular deficiencies. A growing number of case reports and clinical series have proven the efficacy of mandibular DO as an augmentative technique in patients with hemifacial microsomia (HFM). Although DO has become a part of the treatment algorithm for many patients with HFM, surgeons have been reluctant to apply the technique in patients with complete agenesis of the ascending mandibular ramus and condyle (grade III HFM). In the following cases, mandibular DO was successfully performed in two patients with grade III HFM. Preoperative images and intraoperative findings confirmed that both patients lacked the entire ascending mandibular ramus and condyle on the affected side. After unilateral multiplanar DO, both patients showed new bone formation within the distraction gap and development of a pseudoarthrosis between the proximal segment of the mandible and the skull base. Facial symmetry improved dramatically, and speech and mandibular excursion were maintained. The patients have been followed for 1 to 2 years after distraction with durable functional and esthetic outcomes. Mandibular DO offers many advantages compared with rib grafting, including avoidance of donor site morbidity, application in patients who are not candidates for graft harvest, and use after rib graft failure. The following cases support the use of mandibular DO as a mechanism of endogenous tissue engineering in patients with complete agenesis of the ascending mandibular ramus and condyle.
Child↗