Stable fixation using absorbable sutures in craniofacial surgery in patients over 24 months of age-a retrospective study.

PURPOSE: In craniofacial surgery, the stable fixation of transposed bone segments is crucial in order to ensure good long-term results. The use of absorbable material in fixation avoids the need for a second surgery, which would otherwise be required to remove osteosynthesis material. The authors of the present manuscript have already demonstrated that absorbable sutures ensure the stable fixation of bone segments in patients up to 24 months of age. However, it has thus far remained unclear whether stable fixation is possible in older patients by using only absorbable sutures due to the slower bone remodelling and prolonged healing time in this cohort. METHOD: For the present study, osteosynthesis was performed in 50 patients ranging from 25.7 to 192.1 months of age (mean, 61.4 ± 21.7 months) using solely absorbable sutures (PDS II®, Ethicon, Germany). Post-operative stability and possible restrictions-such as foreign body reactions-were evaluated within clinical and radiological routine follow-ups. RESULTS: All children demonstrated clinically and radiologically stable osteosynthesis both directly post-operatively and in follow-ups. No significant foreign body reaction could be seen. CONCLUSION: The present study demonstrates-for the first time-that absorbable sutures with a longer absorption period are also very well suited for the fixation of bone segments in patients over 24 months of age. The sole use of absorbable sutures in children over 24 months of age is a safe procedure with nearly no foreign body reactions. The procedure enables stable and highly cost-effective osteosynthesis without altering the osteotomy design.

Using a 3D asymmetry index as a novel form for capturing complex three-dimensionality in positional plagiocephaly.

Positional plagiocephaly (PP) is the most common skull deformity in infants. Different classification systems exist for graduating the degree of PP, but all of these systems are based on two-dimensional (2D) parameters. This limitation leads to several problems stemming from the fact that 2D parameters are used to classify the three-dimensional (3D) shape of the head. We therefore evaluate existing measurement parameters and validate a newly developed 3D parameter for quantifying PP. Additionally, we present a new classification of PP based on a 3D parameter. 210 patients with PP and 50 patients without PP were included in this study. Existing parameters (2D and 3D) and newly developed volume parameters based on a 3D stereophotogrammetry scan were validated using ROC curves. Additionally, thresholds for the new 3D parameter of a 3D asymmetry index were assessed. The volume parameter 3D asymmetry index quantifies PP equally as well as the gold standard of 30° diagonal difference. Moreover, a 3D asymmetry index allows for a 3D-based classification of PP. The 3D asymmetry index can be used to define the degree of PP. It is easily applicable in stereophotogrammetric datasets and allows for comparability both intra- and inter-individually as well as for scientific analysis.

Subjective perception of craniofacial growth asymmetries in patients with deformational plagiocephaly.

OBJECTIVES: The present investigation aimed to evaluate the subjective perception of deformational cranial asymmetries by different observer groups and to compare these subjective perceptions with objective parameters. MATERIALS AND METHODS: The 3D datasets of ten infants with different severities of deformational plagiocephaly (DP) were presented to 203 observers, who had been subdivided into five different groups (specialists, pediatricians, medical doctors (not pediatricians), parents of infants with DP, and laypersons). The observers rated their subjective perception of the infants' cranial asymmetries using a 4-point Likert-type scale. The ratings from the observer groups were compared with one another using a multilevel modelling linear regression analysis and were correlated with four commonly used parameters to objectively quantify the cranial asymmetries. RESULTS: No significant differences were found between the ratings of the specialists and those of the parents of infants with DP, but both groups provided significantly more asymmetric ratings than did pediatricians, medical doctors, or laypersons. Moreover, the subjective perception of cranial asymmetries correlated significantly with commonly used parameters for objectively quantifying cranial asymmetries. CONCLUSIONS: Our results demonstrate that different observer groups perceive the severity of cranial asymmetries differently. Pediatricians' more moderate perception of cranial asymmetries may reduce the likelihood of parents to seek therapeutic interventions for their infants. Moreover, we identified some objective symmetry-related parameters that correlated strongly with the observers' subjective perceptions. CLINICAL RELEVANCE: Knowledge about these findings is important for clinicians when educating parents of infants with DP about the deformity.

Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children.

BACKGROUND: Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severity. HPP affects patients of all ages. In children HPP-related musculoskeletal symptoms may mimic rheumatologic conditions and diagnosis is often difficult and delayed. To improve the understanding of HPP in children and in order to shorten the diagnostic time span in the future we studied the natural history of the disease in our large cohort of pediatric patients. This single centre retrospective chart review included longitudinal data from 50 patients with HPP diagnosed and followed at the University Children's Hospital Wuerzburg, Germany over the last 25 years. RESULTS: The cohort comprises 4 (8%) perinatal, 17 (34%) infantile and 29 (58%) childhood onset HPP patients. Two patients were deceased at the time of data collection. Diagnosis was based on available characteristic clinical symptoms (in 88%), low alkaline phosphatase (AP) activity (in 96%), accumulating substrates of AP (in 58%) and X-ray findings (in 48%). Genetic analysis was performed in 48 patients (31 compound heterozygous, 15 heterozygous, 2 homozygous mutations per patient), allowing investigations on genotype-phenotype correlations. Based on anamnestic data, median age at first clinical symptoms was 3.5 months (min. 0, max. 107), while median time to diagnosis was 13 months (min. 0, max. 103). Common symptoms included: impairment of motor skills (78%), impairment of mineralization (72%), premature loss of teeth (64%), musculoskeletal pain and craniosynostosis (each 64%) and failure to thrive (62%). Up to now 20 patients started medical treatment with Asfotase alfa. CONCLUSIONS: Reported findings support the clinical perception of HPP being a chronic multi-systemic disease with often delayed diagnosis. Our natural history information provides detailed insights into the prevalence of different symptoms, which can help to improve and shorten diagnostics and thereby lead to an optimised medical care, especially with promising therapeutic options such as enzyme-replacement-therapy with Asfotase alfa in mind.

Craniofacial growth in infants with deformational plagiocephaly: does prematurity affect the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment?

OBJECTIVE: Although prematurity is a risk factor for developing deformational plagiocephaly (DP), to our knowledge, there are no studies that have analyzed the impact of a premature birth on the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment. MATERIALS AND METHODS: We examined 239 patients with DP who were undergoing head orthosis therapy. Depending on the gestational age, they were assigned to either a premature (gestational age of < 37 weeks) or a full-term (gestational age of ≥ 37 weeks) group. Head shape was analyzed using 3D-stereophotogrammetry at the start and end of treatment. We performed multiple linear regression analyses to evaluate the impact of prematurity on the duration of therapy and the extent of the reduction in asymmetry, taking age and the initial asymmetry of an infant's head into account. RESULTS: Head orthosis therapy led to a significant reduction in asymmetry in both groups. Using multiple linear regression analyses, we demonstrated that age at the start of treatment, the initial asymmetry and prematurity, significantly influenced the duration of therapy. Patients who were born at an earlier gestational age experienced a shorter treatment length. However, prematurity did not affect the extent of the reduction in cranial asymmetry that was achieved. CONCLUSIONS: Along with age at the start of treatment and the initial asymmetry, prematurity is significantly correlated with the duration of head orthosis therapy, but not with the extent of the reduction in asymmetry achieved. CLINICAL RELEVANCE: Knowledge of these findings is important for clinicians when planning treatment and discussing the effectiveness of head orthosis therapy with the parents of premature infants with DP.

Head orthosis therapy in positional plagiocephaly: longitudinal 3D-investigation of long-term outcomes, compared with untreated infants and with a control group.

Background: As there are very few long-term studies on the effects of head orthosis on deformational plagiocephaly (DP), we investigated the outcomes of patients, including facial symmetry and dental occlusion. Methods: Forty-five infants with DP [cranial vault asymmetry index (CVAI) > 3.5 per cent] were divided into two groups: one treated with head orthosis (32 infants) and another without (13 infants). Another group without head asymmetry (CVAI ≤ 3.5 per cent) served as control. Using 3D-stereophotogrammetry, cranial asymmetry was analysed using symmetry-related variables [CVAI, posterior cranial asymmetry index (PCAI), and ear offset]. Data acquisition was performed before (T1) and at the end of treatment (T2), and at the age of 4 years (T3) for the treated group and at T1 and T3 for the remaining groups. Parameters of facial symmetry and dental occlusion were assessed at T3 for infants with DP. Results: Symmetry-related variables (∆T1-T3) improved significantly more in the treated than the control group, whereas these parameters did not differ significantly between the untreated and control group. Comparing the treated and untreated groups between T1 and T3, the reduction in the asymmetry at the treated group was significantly higher for the CVAI and PCAI. In follow-up, the untreated group showed higher incidences of facial asymmetries than the treated group. Seventy-five per cent of all lateral crossbites found in patients with DP were contralateral to the posterior flattening. Limitations: Due to ethical reasons, the investigation is a non-randomized study. Parameters of facial symmetry were only assed for the treated and untreated groups. Conclusion: Head orthosis therapy in patients with DP leads to significantly better long-term outcomes. Facial asymmetries are more frequent in patients with DP who do not receive this treatment.

Cranial growth in infants─A longitudinal three-dimensional analysis of the first months of life.

PURPOSE: In the first months of life, any deviation from a physiological growth pattern can cause skull deformity. As there has not been any longitudinal three-dimensional (3D) study investigating the physiological growth of the infant skull, the aim of the present study was to acquire such data. MATERIALS AND METHODS: We performed 3D stereophotogrammetric scans of 40 infants without cranial asymmetry at four regular 2-month intervals from the 4th to the 10th month of age. Six growth-related parameters (circumference, length, width, height, cephalic index [CI; width-length ratio] and total head volume) were used to analyse skull growth longitudinally. RESULTS: With exception of the CI, all parameters showed significant increases, with maximum percentage growth from the 4th to the 6th month. The CI initially remained unchanged until the 6th month, before showing a significant reduction that continued throughout the study period. Male infants had larger heads than female infants, but a similar width-length ratio at all measurement times. CONCLUSION: This prospective study is the first longitudinal 3D analysis to examine the physiological growth dynamics of infants' heads within the first months of life. Understanding patterns of skull growth in all three dimensions is important for gaining further insights into physiological and pathophysiological skull development.

Does shape affect function? Articulatory skills in babbling of infants with deformational plagiocephaly.

PURPOSE: The purpose of this study was to quantitatively analyse pre-speech/early language skills in healthy full-term infants with moderate or severe deformational plagiocephaly (DP) and in infants without any skull asymmetry. METHODS: At 6 and 12 months, 51 children with DP (41 moderate, 10 severe cases) were studied, along with 15 infants serving as control. Deformational plagiocephaly (DP) was objectively determined based on cranial vault asymmetry (CVA) using 3D stereophotogrammetry (3dMDhead System® and Analytics 4.0, Cranioform®). Articulatory skills in babbling were assessed using the articulatory skill (ART-index) and mean syllable number (MSN). At 12 months, standardized parental questionnaires were used to evaluate early language outcomes. RESULTS: Overall, 3546 vocalizations were studied. Statistical tests did not reveal any significant differences of the ART-index between the three groups (ANOVA, F[2,63] = 0.24, p = 0.24). MSN likewise did not differ between the three shape groups (Kruskal-Wallis, p = 0.84). Among the children assigned to the at-risk group for language outcomes at 12 months were seven members of the symmetrical shape group (vs. seven assigned to the normally developing group), nine of the moderate DP group (vs. 27), and one of the severe DP group (vs. six). Fisher's exact test was used to analyse whether helmet therapy in the moderate DP group affected the results by influencing language outcomes, but did not reveal any significant influence (p = 0.712). CONCLUSIONS: The results of this study do not support arguments suggesting that DP is a cognitive risk condition. The suggestion that a direct neurophysiological relationship exists between a DP condition and a cognitive developmental delay remains controversial.

Six month-old infants with deformational plagiocephaly do not differ from unaffected infants with respect to vocal control.

OBJECTIVES: The recommendation of a supine sleeping position led to a significant reduction of SIDS, but increased positional skull deformities (DP). Here, a quantitative analysis of babbling aims to complement previous studies of language-relevant competence based on items of the Bayley-scales that suggested the presence of developmental language delays in DP infants. Measures of fundamental frequency variability as proxies for vocal control are well suited for testing this assumption, since the laryngeal neuro-muscular system matures early and is coupled with brain function while working rapidly in coordinating the structures and mechanisms involved in infant sound production. METHODS: Sixty-six healthy, full-term infants with normal hearing and a monolingual background took part: (1) moderately asymmetrical DP group - N = 41; 21 male; (2) severely asymmetrical DP group - N = 10; 8 male; and (3) controls - N = 15; 5 male (group assignment based on stereophotogrammetric 360° scans). Fundamental frequency (fo) measures were taken as proxies for vocal control skills during babbling. RESULTS: A MANOVA revealed no significant multivariate effect for the shape group, Wilks' λ = 0.86, F(2, 63) = 1.21, p = 0.30, η2 = 0.07 (medium effect-size). The results do not support previous findings based on Bayley scale evaluations that suggested a negative impact of DP on language development during infancy. CONCLUSIONS: A strong link between DP and brain dysfunction affecting vocal control, which would cause deviations in otherwise healthy DP infants, was not observed. Objective long-term studies of sound production are necessary to identify and/or understand the potential consequences of DP on early language development.

Positional Skull Deformities.

BACKGROUND: Especially in the first 6 months of life, skull deformities manifesting as a uni- or bilateral flattening of the occiput often give rise to questions of differential diagnosis and potential treatment. In this review, the authors summarize the current understanding of risk factors for this condition, and the current state of the relevant diagnostic assessment and options for treatment. METHODS: The recommendations given in this selective review of the literature are based on current studies and on existing guidelines on the prevention of sudden infant death, the recommendations of the German Society for Pediatric Neurology (Deutsche Gesellschaft für Neuropädiatrie), and the American guidelines on the treatment of positional plagiocephaly in infancy. RESULTS: Pre-, peri-, and postnatal risk factors can contribute to the development of positional skull deformities. These deformities can be diagnosed and classified on the basis of their clinical features, supplemented in unclear cases by ultrasonography of the cranial sutures. The putative relationship between positional skull deformities and developmental delay is currently debated. The main preventive and therapeutic measure is parent education to foster correct positioning habits (turning of the infant to the less favored side; prone positioning on occasion when awake) and beneficial stimulation of the infant (to promote lying on the less favored side). If the range of motion of the head is limited, physiotherapy is an effective additional measure. In severe or refractory cases, a skull orthosis (splint) may be useful. CONCLUSION: The parents of children with positional skull deformities should be comprehensively informed about the necessary preventive and therapeutic measures. Treatment should be initiated early and provided in graded fashion, according to the degree of severity of the problem. Parental concern about the deformity should not be allowed to lead to a rejection of the reasonable recommendation for a supine sleeping position.

Head Orthosis Therapy in Positional Plagiocephaly: Influence of Age and Severity of Asymmetry on Effect and Duration of Therapy.

BACKGROUND: Only a few studies investigating the optimal time point at which to start orthotic treatment for deformational plagiocephaly take into account the severity of skull asymmetry. The present study performs a three-dimensional analysis of the effects of age and severity of asymmetry on the final outcome. METHODS: A total of 144 patients with deformational plagiocephaly treated by molding orthosis were examined and divided into three age groups (group I, <24 weeks; group II, ≥24 to <32 weeks; and group III, ≥32 weeks) and two severity levels (mild to moderate, 30-degree cranial vault asymmetry ≥3 mm to ≤12 mm; and moderate to severe, 30-degree cranial vault asymmetry >12 mm). The extent of the reduction of asymmetry was analyzed using three-dimensional stereophotogrammetry. RESULTS: Therapy with molding orthosis led to a significant reduction in asymmetry in all defined age groups. Efficacy of reduction decreased with increasing age. Successful treatment (cranial vault asymmetry index <3.5 percent) was achieved in 83, 69, and 40 percent of patients with mild to moderate asymmetry in groups I, II, and III, respectively; and in 50, 30, and 7 percent of patients with moderate to severe asymmetry in groups I, II, and III, respectively. The average duration of treatment increased from 18.6 weeks to 25.3 weeks (age groups I and III). CONCLUSION: Age at the beginning of treatment and severity of asymmetry have a definite impact on the duration and effectiveness of molding orthosis therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. METHODS: We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. RESULTS: Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. CONCLUSIONS: This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma.

Muenke syndrome: An international multicenter natural history study.

Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal, and calcaneal fusions, and behavioral differences. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings. Muenke syndrome constitutes the most common syndromic form of craniosynostosis, with an incidence of 1 in 30,000 births and is defined by the presence of the p.Pro250Arg mutation in FGFR3. Participants were recruited from international craniofacial surgery and genetic clinics. Affected individuals, parents, and their siblings, if available, were enrolled in the study if they had a p.Pro250Arg mutation in FGFR3. One hundred and six patients from 71 families participated in this study. In 51 informative probands, 33 cases (64.7%) were inherited. Eighty-five percent of the participants had craniosynostosis (16 of 103 did not have craniosynostosis), with 47.5% having bilateral and 28.2% with unilateral synostosis. Females and males were similarly affected with bicoronal craniosynostosis, 50% versus 44.4% (P = 0.84), respectively. Clefting was rare (1.1%). Hearing loss was identified in 70.8%, developmental delay in 66.3%, intellectual disability in 35.6%, attention deficit/hyperactivity disorder in 23.7%, and seizures in 20.2%. In patients with complete skeletal surveys (upper and lower extremity x-rays), 75% of individuals were found to have at least a single abnormal radiographical finding in addition to skull findings. This is the largest study of the natural history of Muenke syndrome, adding valuable clinical information to the care of these individuals including behavioral and cognitive impairment data, vision changes, and hearing loss.

Perception of children's faces with unilateral coronal synostosis--an eye-tracking investigation.

PURPOSE: Premature unilateral coronal craniosynostosis results in distinctive cranial and facial abnormalities of varying severity, including orbital dystopia and an abnormal head shape. As the face is affected, these children may encounter stigmatization. To avoid this scenario, many parents elect for their child to undergo surgical correction. Laypeople's perception of children with either untreated or treated unilateral coronal craniosynostosis (UCS) has not yet been objectively evaluated. METHODS: This study introduces eye tracking as an objective instrument in order to evaluate the perception of 14 children with coronal synostosis, both pre- and postoperatively. Age-matched healthy children served as a control group. Using standardized photos, the involuntary eye movements and the fixations of 30 unaffected laypeople were evaluated. RESULTS: In the untreated children, whose faces were characterized by striking orbital dystopia, the eyes drew more attention than those of the healthy children. The results of our study demonstrate that the operative correction of unilateral coronal synostosis results in the normalization of the asymmetry of the fronto-orbital region, whereas the C-shaped deformity of the midface, which is not addressed via surgery, subsequently attracts more attention. CONCLUSION: Eye tracking objectively evaluates both the perception of craniofacial abnormalities and the extent of the approximation of normality after surgical correction. We introduce eye tracking as an objective measurement tool for craniofacial abnormalities for the first time.

Diagnostic features of prematurely fused cranial sutures on plain skull X-rays.

PURPOSE: The characteristic features of prematurely fused craniosynostosis in plain radiographs have already been described in literature, but there is no clinical trial investigating the individual features of every single form of craniosynostosis. We described suture-specific characteristics as well as its frequency of appearance in plain radiographs in every different form of craniosynostosis. Intraoperative findings served as control to confirm the diagnosis. METHODS: One hundred twenty-seven children with prematurely fused cranial sutures who underwent a skull X-ray from 2008 to 2012 were investigated in the present study. In detail, 34 children with frontal, 60 with sagittal, 13 with unilateral and 14 with bilateral coronal synostosis and 3 with unilateral lambdoid craniosynostosis as well as 3 children with a bilateral lambdoid synostosis were included. RESULTS: Typical radiological characteristics in craniosynostosis exist. These features as well as its frequency in craniosynostosis in plain skull radiographs are presented. In all cases, these typical features enabled a correct diagnosis, which was confirmed by intraoperative findings. CONCLUSION: The frequency of the appearance of typical features is listed and may serve as a "mental internal check list" in the radiological approach to craniosynostosis. The study points out the value of plain skull X-rays as it enabled proper diagnosis in all investigated 127 cases.

Executive Function and Adaptive Behavior in Muenke Syndrome.

OBJECTIVE: To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. STUDY DESIGN: Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition [ABAS-II]). RESULTS: Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (<25th percentile). Multiple regression analysis did not identify craniosynostosis as a predictor of BRIEF (P = .70) or ABAS-II scores (P = .70). In the sibling pair analysis, affected siblings performed significantly poorer on the BRIEF General Executive Composite and the ABAS-II General Adaptive Composite. CONCLUSION: Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings.

Occipital plagiocephaly: unilateral lambdoid synostosis versus positional plagiocephaly.

OBJECTIVE: We defined parameters that could differentiate between positional and synostotic plagiocephaly and defined a diagnostic chart for decision making. DESIGN: Prospective study. SETTING: We examined 411 children with non-syndromic skull abnormalities between January 2011 and December 2012. PARTICIPANTS: A total of 8 infants under 1 year of age with proven unilateral non-syndromic lambdoid synostosis (LS) and 261 children with positional deformity were examined to outline the specific clinical features of both diagnoses. After clinical examination, an ultrasound revealed either a closed suture suggestive of LS or a patent lambdoid suture suggestive of positional deformity. For patients with synostosis, plain radiographs, MR imaging and follow-up examinations were performed. In cases of open sutures, only follow-ups were completed. MAIN OUTCOME MEASURE: Clinical, imaging, genesis and treatment differences between positional plagiocephaly and LS. RESULTS: In all 8 cases of unilateral LS and 258 cases of positional plagiocephaly, the diagnosis was established by clinical examination alone. In three cases of positional plagiocephaly, diagnosis was determined after an additional ultrasonography. MR imaging revealed a unilateral tonsillar herniation in five of the eight children with LS and hydrocephalus in one child. CONCLUSIONS: We have suggested a list of clinical features that specify the underlying cause of posterior plagiocephaly. An additional ultrasound scanning confirmed the diagnosis without any risks of ionising radiation or sedation as in a CT scan.