Intracranial volume and whole brain volume in infants with unicoronal craniosynostosis.

OBJECTIVE: Craniosynostosis has been hypothesized to result in alterations of the brain and cerebral blood flow due to reduced intracranial volume, potentially leading to cognitive deficits. In this study we test the hypothesis that intracranial volume and whole brain volume in infants with unilateral coronal synostosis differs from those in unaffected infants. DESIGN: Our study sample consists of magnetic resonance images acquired from 7- to 72-week-old infants with right unilateral coronal synostosis prior to surgery (n  =  10) and age-matched unaffected infants (n  =  10). We used Analyze 9.0 software to collect three cranial volume measurements. We used nonparametric tests to determine whether the three measures differ between the two groups. Correlations were calculated between age and the three volume measures in each group to determine whether the growth trajectory of the measurements differ between children with right unicoronal synostosis and unaffected infants. RESULTS: Our results show that the three volume measurements are not reduced in infants with right unicoronal synostosis relative to unaffected children. Correlation analyses between age and various volume measures show similar correlations in infants with right unicoronal synostosis compared with unaffected children. CONCLUSIONS: Our results show that the relationship between brain size and intracranial size in infants with right unicoronal synostosis is similar to that in unaffected children, suggesting that reduced intracranial volume is not responsible for alterations of the brain in craniosynostosis.

Development and validation of GC/MS method for determination of pramipexole in rat plasma.

A simple, rapid and sensitive method has been developed and validated for the determination of pramipexole in rat plasma by using gas chromatography mass spectrometry. The lower limit of quantification (LLOQ) is superior to the other reported LC-MS/MS methods. After being made alkaline with NaOH, plasma samples (0.1 mL) were subjected to liquid-liquid extraction using methyl-t-butyl ether. Analytes were determined using electron impact ionization in a single quadrupole mass spectrometer. GC/MS was performed in the selected ion monitoring mode using target ions at m/z 211, 212 and 152 for pramipexole and m/z 194 and 165 for caffeine as internal standard. A linear calibration curve was plotted over the range of 20-1000 pg/mL for pramipexole (r(2) > 0.996). The LLOQ was 20.0 pg/mL, respectively, which offered high sensitivity and selectivity enough for bioanalytical investigation. Inter- and intraday precisions ranged from 0.3 to 8.8% and from 0.9 to 11.33%, respectively. The recovery of pramipexole from plasma ranged from 82.4 ± 7.1 to 87.8 ± 5.7%. The method fulfills all standards required for bioanalytical methods and can be successfully applied to a pharmacokinetic study of pramipexole in rats.

Remediation potential of certain wild and native species for manganese and iron contaminated waste.

Green house studies were carried out to test the suitability of certain plant species for the phytostabilization of manganese mine waste. A number of wild and native plants were selected and raised directly or after suitable amendments with NPK and capping with 10% soil on the manganese mine waste. Only few of the plants survived and showed a tendency to establish and stabilize the waste. In 10% soil + 2 NPK amended waste, Ziziphus mauritiana showed good growth and resulted in an increase of 1966.66% after a period of six months.

Outcomes and complications based on experience with resorbable plates in pediatric craniosynostosis patients.

The structure and functional relationship of polymers have long been the purview of engineers and polymer chemists. Bioabsorbable fixation devices have been used for decades as dissolvable suture meshes and, recently, routinely by orthopedic surgeons. During the past decade, bioabsorbable fixation systems have become available for use by craniomaxillofacial surgeons for cranial vault remodeling. This study evaluates the application of a bioabsorbable fixation system in reconstructive craniofacial procedures in a pediatric population. We reviewed 146 cases of cranial vault reconstruction including 98 boys and 48 girls ranging from 2 months to 16 years (mean, 15 months) in age. The procedures were performed for 6 years between January 1998 and June 2004. Bioabsorbable plates and screws were used in each case; most of these cases were craniosynostosis reconstructions. There were 69 cases of frontal sagittal craniosynostosis, 36 metopic, 20 unicoronal, 12 bicoronal, 5 lamboid, 2 deformational plagiocephaly, and 2 multiple fusion of sutures. Postoperative evaluation consisted of clinical examination and three-dimensional computed tomography scan reconstructions at 3, 6, and 12 months. Items specifically screened for on the clinical examination included wound healing, signs of infection, and palpability of implant through the skin. Six patients had palpable plates, 2 patients had palpable screw, and 5 patients had infection at the incision site (of which only 3 were treated with inpatient care including incision drainage and intravenous antibiotics). Our experience has been overwhelmingly positive, and we feel that our results suggest that resorbable fixation is a superior option in pediatric plastic and craniofacial surgery.

Genetics of craniosynostosis.

Craniosynostosis is a defect of the skull caused by early fusion of one or more of the cranial sutures and affects 3 to 5 individuals per 10,000 live births. Craniosynostosis can be divided into two main groups: syndromic and nonsyndromic. Nonsyndromic craniosynostosis is typically an isolated finding that is classified according to the suture(s) involved. Syndromic craniosynostosis is associated with various dysmorphisms involving the face, skeleton, nervous system, and other anomalies and is usually accompanied by developmental delay. More than 180 syndromes exist that contain craniosynostosis. Secondary effects of craniosynostosis may include vision problems and increased intracranial pressure, among others. The molecular basis of many types of syndromic craniosynostosis is known, and diagnostic testing strategies will often lead to a specific diagnosis.

The role of donor site angiography before mandibular reconstruction utilizing free flap.

This study was initiated to establish a treatment algorithm for preoperative evaluation of donor sites prior to the harvest of free osteocutaneous flaps, in the setting of complex mandibulofacial reconstruction. A total of 29 consecutive patients were treated between 1999 and 2003 in a university-based setting. Reconstructions were completed using either a free fibula osteocutaneous flap or a radial forearm free flap. Functional and aesthetic results were determined by completing a thorough patient physical examination postoperatively. We hypothesized that a routine preoperative angiogram at the donor site was unnecessary. The Allen's test was the only preoperative evaluation completed in the 13 patients undergoing the free radial forearm reconstruction. In the remaining 16 patients undergoing free fibula reconstruction, a thorough physical examination was completed, along with noninvasive Doppler examinations. No angiograms were obtained. Using this systematic approach, no ischemic complications were observed at the donor site. Only two complete flap losses were seen, one in each group, due to microvascular thrombosis. We conclude that preoperative assessment of the donor site(s) with only an Allen's test in the free radial forearm group and a thorough pulse exam and a noninvasive Doppler in the free fibula group appear adequate. Routine preoperative angiogram of the donor extremity may be unnecessary and place the patient at additional risk for associated complications.

Phenotypic integration of neurocranium and brain.

Evolutionary history of Mammalia provides strong evidence that the morphology of skull and brain change jointly in evolution. Formation and development of brain and skull co-occur and are dependent upon a series of morphogenetic and patterning processes driven by genes and their regulatory programs. Our current concept of skull and brain as separate tissues results in distinct analyses of these tissues by most researchers. In this study, we use 3D computed tomography and magnetic resonance images of pediatric individuals diagnosed with premature closure of cranial sutures (craniosynostosis) to investigate phenotypic relationships between the brain and skull. It has been demonstrated previously that the skull and brain acquire characteristic dysmorphologies in isolated craniosynostosis, but relatively little is known of the developmental interactions that produce these anomalies. Our comparative analysis of phenotypic integration of brain and skull in premature closure of the sagittal and the right coronal sutures demonstrates that brain and skull are strongly integrated and that the significant differences in patterns of association do not occur local to the prematurely closed suture. We posit that the current focus on the suture as the basis for this condition may identify a proximate, but not the ultimate cause for these conditions. Given that premature suture closure reduces the number of cranial bones, and that a persistent loss of skull bones is demonstrated over the approximately 150 million years of synapsid evolution, craniosynostosis may serve as an informative model for evolution of the mammalian skull.

Neurodevelopmental delays in children with deformational plagiocephaly.

BACKGROUND: The purpose of this study was to determine whether, in fact, infants with deformational plagiocephaly, or plagiocephaly without synostosis, demonstrated cognitive and psychomotor developmental delays when compared with a standardized population. Through this study, we chose to expand upon our earlier findings from 2001 on patients with deformational plagiocephaly. METHODS: The study population includes a total of 110 consecutive patients, prospectively followed then retrospectively reviewed. Each infant was assessed using the Bayley Scales of Infant Development-II scoring system. The developmental analysis was categorized as either mental or psychomotor using the mental developmental index or the psychomotor developmental index, respectively. These infants were subcategorized into four groups: accelerated, normal, mild, or severely delayed. The groups were then compared with a standardized Bayley's age-matched population, using chi-square test goodness-of-fit tests. RESULTS: Infants with deformational plagiocephaly were found to have significantly different psychomotor development indexes and mental developmental indexes when compared with the standardized population (p < 0.0001; p < 0.0001). With regards to the mental developmental index scores, none of the infants with deformational plagiocephaly were accelerated, 90 percent were normal, 7 percent were mildly delayed, and 3 percent were severely delayed. With regards to the psychomotor development index scores, none of infants were accelerated, 74 percent were normal, 19 percent were mildly delayed, and 7 percent were severely delayed. CONCLUSIONS: This study indicates that before any intervention, infants with deformational plagiocephaly show significant delays in both mental and psychomotor development. Also of particular note is that no child with deformational plagiocephaly showed accelerated development.

Brain morphology in nonsyndromic unicoronal craniosynostosis.

Studies of isolated craniosynostosis have shown biomechanical and biochemical influences on the craniofacial phenotype, resulting from both genetic and epigenetic factors. Much less attention has been directed toward the morphology of the brain, despite the interactive nature of the developing skull and developing brain. The aim of this study is to define the morphology of the brain in nonsyndromic unilateral coronal synostosis (UCS) in order to form more complete hypotheses about the cause of craniosynostosis. Landmark coordinate data were collected from 3D magnetic resonance image reconstructions of the brain in a sample of UCS patients and an age-matched morphologically normal cohort. These data were analyzed using Euclidean distance matrix analysis. The results of our study demonstrate that despite the basic similarity of overall shape of the brain and skull in UCS, the effects of craniosynostosis on the brain are not localized to structures immediately adjacent to the fused suture or to the endocranial surface of the skull. Rather, alterations are observed throughout the volume of the brain, with subcortical structures altered in conjunction with cortical changes. These results indicate that the morphological correlates are different for brain and skull and suggest that there is a large degree of independence in the developmental trajectories of the brain and skull.

Visual field defects in deformational posterior plagiocephaly.

PURPOSE: We sought to determine whether visual field abnormalities occur in infants with deformational posterior plagiocephaly and to assess whether there is a relationship between the severity and laterality of visual field abnormalities with the severity and laterality of skull deformity. METHODS: A retrospective chart review was performed on 40 consecutive infants with deformational posterior plagiocephaly. Each was tested with standardized binocular arc perimetry in the horizontal plane. Sixteen patients also had 3-dimensional computed tomography of the skull. Hemifield asymmetry of >/=20 degrees and/or a decrease in hemifield values by >/=20 degrees from established normal patients was considered abnormal. Visual field data from study patients was plotted against previously published normative data. Graphs comparing visual field defects and laterality to cranial asymmetry also were generated. RESULTS: Thirty-five percent of infants with deformational posterior plagiocephaly had constriction of one or both hemifields by at least 20 degrees from established normal patients. Hemifield asymmetry of 20 degrees or more was found in 17.5% of infants tested. There was a significant difference in the worse hemifield values measured in each patient and the standard visual fields obtained from normative data ( P = 0.036). There was no correlation between the laterality of the visual fields to the laterality of the defects. A correlation between severity of hemifield constriction and % asymmetry on computed tomography was noted ( P = 0.209). CONCLUSIONS: Deformational posterior plagiocephaly may affect visual field development but neither the laterality nor the severity of skull deformity is predictive of the severity of visual field defects.

Neonatal distraction surgery for micrognathia reduces obstructive apnea and the need for tracheotomy.

The objective of the study was to assess the effectiveness of neonatal mandibular distraction in treatment of obstructive sleep apnea in the perinatal period in preventing a tracheotomy. This was a prospective study of 17 infants at two centers with severe micrognathia who demonstrated obstructive sleep apnea refractory to conservative therapy. Age at surgery varied from 5 to 120 days. Distraction was performed at a rate of 2 mm/d. After distraction, callus consolidation was allowed for 4 to 6 weeks, and the device was then removed. Each child underwent a three-dimensional computed tomography scan before surgery and approximately 3 months after surgery. Of the 17 patients, 14 successfully underwent extubation and demonstrated significant improvement in the obstructive sleep apnea. Postoperative horizontal ramus length increased from 23.3 to 34.8 mm after surgery. Mean maxillary mandibular discrepancy was 8.28 mm before surgery and 2.2 mm after surgery. Ten infants who underwent pre- and postoperative polygraphic studies showed improvement in obstructive apnea. Three patients had postoperative polysomnographic studies only; the results were also within the normal range. The mean follow-up interval was 16.5 months (range: 8-48 months). Neonatal distraction is an effective method for treatment of micrognathia with obstructive sleep apnea in the perinatal period in preventing a tracheotomy.

Management of craniosynostosis.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Review the etiopathogenesis of craniosynostosis and craniofacial anomalies. 2. Develop a basic understanding of the clinical manifestations and diagnosis of craniofacial anomalies. 3. Describe the surgical principles of managing craniosynostosis and craniofacial anomalies.Craniosynostosis, or the premature closure of calvarial sutures, results in deformed calvaria at birth. Although the etiology of craniosynostosis is currently unknown, animal experiments and a recent interest in molecular biology point toward interplay between the dura and the underlying brain. This interaction occurs by means of a local alteration in the expression of transforming growth factor, MSX2, fibroblast growth factor receptor, and TWIST. The fused suture restricts growth of the calvaria, thus leading to a characteristic deformation, each associated with a different type of craniosynostosis. Uncorrected craniosynostosis leads to a continuing progression of the deformity, and in some cases, an elevation of intracranial pressure. Clinical examination should include not only an examination of the skull but also a general examination to rule out the craniofacial syndromes that accompany craniosynostosis. Because deformational plagiocephaly, or plagiocephaly without synostosis, occurs secondary to sleeping in the supine position during the early perinatal period, the physician should be aware of this abnormality. Treatment for deformational plagiocephaly is conservative when compared with treatment for craniosynostosis, which requires surgery. Appropriate investigations should include genetic screening, radiologic examination with a computerized tomographic scan, and neurodevelopmental analysis. Surgical intervention should be performed during infancy, preferably in the first 6 months of postnatal life, to prevent the further progression of the deformity and possible complications associated with increased intracranial pressure. The principles of surgical intervention are not only to excise the fused suture but also to attempt to normalize the calvarial shape. Long-term follow-up is critical to determine the effect of the surgical outcome.