Tilmann Schweitzer

Extraneural metastases of primary brain tumors.

Extraneural metastasis (ENM) of primary brain tumors is a rare occurence. Based on a critical analysis of the literature the present review focuses on illustrating special common features of these tumors with regard to immunological, cytokinetical and tumorbiological issues. In this respect much can be learned from the specific conditions following organ transplantation which is extensively discussed.

Avoiding CT scans in children with single-suture craniosynostosis

IntroductionDuring the last decades, computed tomography (CT) has become the predominant imaging technique in the diagnosis of craniosynostosis. In most craniofacial centers, at least one three-dimensional (3D) computed tomographic scan is obtained in every case of suspected craniosynostosis. However, with regard to the risk of radiation exposure particularly in young infants, CT scanning and even plain radiography should be indicated extremely carefully.Material and methodsOur current diagnostic protocol in the management of single-suture craniosynostosis is mainly based on careful clinical examination with regard to severity and degree of the abnormality and on ophthalmoscopic surveillance. Imaging techniques consist of ultrasound examination in young infants while routine plain radiographs are usually postponed to the date of surgery or the end of the first year. CT and magnetic resonance imaging (MRI) are confined to special diagnostic problems rarely encountered in isolated craniosynostosis. The results of this approach were evaluated retrospectively in 137 infants who were referred to our outpatient clinic for evaluation and/or treatment of suspected single suture craniosynostosis or positional deformity during a 2-year period (2008–2009).ResultsIn 133 (97.1%) of the 137 infants, the diagnosis of single-suture craniosynostosis (n = 110) or positional plagiocephaly (n = 27) was achieved through clinical analysis only. Two further cases were classified by ultrasound, while the remaining two cases needed additional digital radiographs. In no case was CT scanning retrospectively considered necessary for establishing the diagnosis. Yet in 17.6% of cases, a cranial CT scan had already been performed elsewhere (n = 16) or had been definitely scheduled (n = 8).ConclusionCT scanning is rarely necessary for evaluation of single-suture craniosynostosis. Taking into account that there is a quantifiable risk of developing cancer in further lifetime, every single CT scan should be carefully indicated.

Spontaneous regression of experimental gliomas--an immunohistochemical and MRI study of the C6 glioma spheroid implantation model.

OBJECTIVE The orthotopic C6 glioma spheroid implantation model has been used to examine factors of neoangiogenesis, growth factor release, and protease expression as well the effect of antitumor agents. The present study systematically investigates the long-term course of orthotopically implanted C6 spheroid gliomas. METHODS Reaggregated C6 spheroid tumors were implanted into the forebrain of 48 male Sprague-Dawley rats (32 immunocompetent, 16 thymectomized). The animals were examined by MRI at postoperative day (POD) 7, 14, 21, 28, 32, 45, 60, and 70. The MRI protocol included a T2-w and T1-w SE sequence before and after application of contrast medium and a CISS 3D sequence for volumetry. A total of six animals were selected after each MR exam from both groups and sacrificed for HE light microscopy and CD8+ T-lymphocyte, ED1+ macrophage, CD31+ endothelial cell immunohistochemistry. RESULTS The tumors progressed to reach a maximum volume on day 28: 0.23 +/- 0.05 ml in the thymectomized and 0.16 +/- 0.021 ml in the immunocompetent group. Tumors then consistently regressed to vanish completely by POD 70. The influx of cytotoxic CD8+ T-lymphocytes correlated with tumor progression and the tumors reached a larger size in the thymectomized group. However, the time course of tumor regression was the same for both groups. CONCLUSION The present data suggest that the orthotopic C6 glioma implanted into Sprague-Dawley rats will progress within a time span of approximately 4 weeks and can then retrogress again spontaneously. This finding has to be taken into account when deciding on a study protocol and the appropriate animal model. The C6 glioma model may be suitable to study the cell biological steps involved in the phenomenon of spontaneous tumor regression.

Three-dimensional analysis of cranial growth from 6 to 12 months of age

The aim of this study was to generate three-dimensional data of the physiological growth of the infants cranium in the significant growth phase from 6 to 12 months of age. In a longitudinal observational study non-invasive 3D data using an optical surface scanner were generated of the entire head of 52 Caucasian infants (27 females and 25 males) between the ages of 6 (T1) and 12 (T2) months. The circumference of the head increased by 6.51 per cent (from 43.50 to 46.33cm). Analysis of width and length showed that the head grows 2.84 per cent more in length, resulting in a decrease in the cranial index of 2.52 per cent (from 83.87 to 81.76 per cent). The highest increment observed was in the total volume of the cranium, with an increase of 18.76 per cent (from 1229.01 to 1459.57cm(3)). Comparison of the left and right sides of the head by measuring the diagonal symmetry difference showed a difference of only 0.37cm. Overall, the symmetry-related parameters showed an almost symmetric development of the cranium in infants. The findings should provide valuable information on physiological growth and development of the infants cranium. Therefore the high growth rate of the cranium in the first year of life suggests that this period is a critical period in which the disruption of developmental processes may have long-lasting effects on the morphology of the cranium with a prognostically unfavourable effect of the further growth of the viscerocranium.

Multi-directional Le Fort III midfacial distraction using an individual prefabricated device.

BACKGROUND Midfacial distraction following Le Fort III osteotomy has become an established procedure for midfacial advancement of syndromic craniosynostosis patients. A frequent difficulty is the precise three dimensional (3D) alignment of the distracted midface and the proper fixation of the distraction device in the midfacial area. In this study we present an individual modification method for commercial distraction devices comprising the establishment of prefabricated fixation plates and parallel connecting pins. MATERIAL Individual prefabricated fixation plates for the zygomatic buttress were combined with two commercial distraction devices. METHOD The fixation plates were made by a casting technique using individual cranial models as templates. The latter were fabricated by the rapid prototyping technique of 3D powder printing. For precise realization of the distraction vector, two commercial devices were combined and attached rigidly to the fixation plates by two parallel pins. RESULT In the clinical routine, the 3D powder printing technique enables the simple fabrication of precise individual cranial models, which are required for manufacturing individual fixation plates. The combination of two commercial distraction devices facilitates the appropriate transfer of complex distraction vectors into the midfacial area. CONCLUSION The technique presented should be useful for a precise multi-directional midfacial distraction following Le Fort III osteotomy.

Three-dimensional analysis of positional plagiocephaly before and after molding helmet therapy in comparison to normal head growth

ObjectiveStereophotogrammetry enables a simple and radiation free longitudinal analysis of skull asymmetries: in a three-dimensional coordinate system various distances (length, breadth, cephalic index, oblique diameters, ear shift, head circumference) can be analyzed. We also defined separate volume sections in order to further quantify the degree of asymmetry in the posterior and anterior components of both sides of the head.Patients and methodsIn 51 infants (mean age, 6 months; SD 0.97) with positional plagiocephaly, we determined these parameters at the beginning as well as at the end of molding helmet therapy (mean therapy time 4.9 months). Thirty-seven infants without positional deformity (mean age, 6.4 months; SD 0.3) served as control group and provided data about what appears to be normal and how these parameters change during growth over a comparable period of time.ResultsCompared with the control group, the plagiocephalic heads were more brachycephalic, but closely approximated the normal shape under molding therapy. The striking volume difference between the left and right posterior sections in the plagiocephalic children (the mean volume of the flattened side being 21 % smaller than the one on the contralateral side) improved as well (to a residual difference of mean 8 %) and ended up with a value close to the control group (mean 6 %).ConclusionThere is a broad clinical application area for stereophotogrammetry analyzing skull morphology: In plagiocephalic infants we demonstrate impressive changes of head shape under molding therapy; in normal-looking infants we describe the extent of unperceived asymmetry.

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.

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

BackgroundMedulloblastoma 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.MethodsWe 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.ResultsBesides 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.ConclusionsThis model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma.

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.

3D stereophotogrammetric analysis of operative effects after broad median craniectomy in premature sagittal craniosynostosis

IntroductionThere is ongoing discussion on the diagnostic methods, the need of surgical treatment, and the surgical strategies for premature craniosynostosis.Materials and methodsThis study examined the operative procedure of a standardized broad median craniectomy, active tilting of the forehead, and bitemporal greenstick fracturing in children with premature sagittal craniosynostosis. To objectively analyze the direct surgical results, we used a 3D stereophotogrammetry scanner, as previously described.ResultsA 3D analysis showed a significant increase in the width, cranial index (CI), head and coronal circumferences, intracranial volume, and cranial base width after surgery. Head length was the only parameter that demonstrated a significant decrease postoperatively. Asymmetry and the 30° diagonal difference showed no significant changes.Conclusion3D stereophotogrammetry is a reliable and valuable tool with no side effects. It demonstrated that the extended surgical procedure achieves good postoperative results with a reduced length and increased width and, therefore, an improved CI. Additionally, the total intracranial volume was significantly increased after surgery.