Ulrich Sure

Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous components of gliosarcomas suggest a common origin from glial cells

Gliosarcomas are morphologically heterogeneous tumors of the central nervous system composed of gliomatous and sarcomatous components. The histogenesis of the latter is still a matter of debate. As mutations of the p53 tumor suppressor gene represent an early event in the development of gliomas, we attempted to determine whether both components of gliosarcomas share identical alterations of the p53 gene. Using single-strand conformation analysis (SSCA) and direct DNA sequencing of the p53 gene, we analyzed dissected gliomatous and sarcomatous parts of 12 formalin-fixed, paraffin-embedded gliosarcomas. The two tumors that contained a p53 alteration were found to carry the identical mutation (exon 5; codon 151, CCC — TCC; codon 173, GTG —> GTA) in the gliomatous and the sarcomatous components. These findings suggest a common origin of the two cellular components from neoplastic glial cells.

Determination of p53 mutations, EGFR overexpression, and loss of p16 expression in pediatric glioblastomas.

Glioblastoma multiforme is a rare neoplasm in children and is often located infratentorially, particularly in the brainstem: Pediatric glioblastomas arise frequently (here 60%) outside the cerebral hemispheres. We investigated 20 pediatric glioblastomas for mutational inactivation of the p53 tumor suppressor gene, loss of p16 protein expression and overexpression of the epidermal growth factor receptor (EGFR). Mutations in the p53 gene were identified in 5/20 (25%) glioblastomas, 4 of which occurred in primary glioblastomas with a clinical history of less than 4 months and neither clinical nor histologic evidence of a less malignant precursor lesion. Loss of p16 expression was detected in 11/18 (61%) glioblastomas. Overexpression of the EGFR was infrequent (2/19, 11%) and included 1 tumor with a p53 mutation. Of 4 secondary glioblastomas that progressed from histologically diagnosed lower grade tumors, one contained a p53 mutation. Our results are at variance with similar studies in adult patients in which primary and secondary glioblastomas are characterized by EGFR overexpression and p53 mutations, respectively, suggesting that the evolution of pediatric glioblastomas follows different genetic pathways.

Transgenic and Knock‐out Mice: Models of Neurological Disease

Besides providing useful model systems for basic science, studies based on modification of the mammalian germ line are changing our understanding of pathogenetic principles. In this article, we review the most popular techniques for generating specific germ line mutations in vivo and discuss the impact of various transgenic models on the study of neurodegenerative diseases.

The supracondylar approach to the jugular tubercle and hypoglossal canal

BACKGROUND Circumscribed lesions of the hypoglossal canal and of the jugular tubercle still remain a surgical challenge. So far, transpetrosal, transcondylar suboccipital, and extreme lateral approaches have been used to access this region. These surgical procedures bear a high risk for neurological deficits. Therefore, we introduce a new minimally invasive extradural approach to the hypoglossal canal that also allows access to the lateral aspects of the jugular tubercle. METHODS After a paramedian retromastoid skin incision, a basal suboccipital craniectomy lateral to the foramen magnum toward the jugular tubercle is performed. With this approach the occipital condyle and the lateral osseous circumference of the foramen magnum are preserved. Drilling extradurally, the dorsal parts of the jugular tubercle are removed. The exposure is extended downward to the posterior margins of the hypoglossal canal and laterally to the jugular bulb, enabling a minimally invasive exposure of the hypoglossal canal, the lateral aspects of the jugular tubercle, and medial aspects of the jugular bulb. RESULTS Using this supracondylar approach, surgical interventions were performed in three patients suffering from a hypoglossal neurinoma, a cholesterol granuloma extending into the jugular tubercle, and a cyst of the hypoglossal canal, respectively. No additional postoperative neurological deficits were seen. CONCLUSIONS The supracondylar approach seems to be useful to gain access to benign lesions of the hypoglossal canal and of the jugular tubercle to decompress tumors or cysts. In contrast to previously reported techniques this approach has a low risk of morbidity. The surgical field, however, is restricted laterally by the jugular bulb, medially and basally by the residual occipital condyle and dorsally by the dura. Therefore, this approach is useful to remove small lesions or to perform extended biopsies. Radical removal of large tumors seems to be problematic using this approach.

Telencephalic transplants in mice: characterization of growth and differentiation patterns

Telencepalic grafting represents a powerful tool for developmental studies and for the investigation of biological features of transgenic brain tissue. The interpretation of grafting experiments. however, requires detailed knowledge of graft biology. Therefore, we have characterzed growth rates, graft size, and differentiation of embryonic telecephalic tissue harvested at various developmental stages and grafted into the caudoputament and lateral ventricles of histocompatible mice. A total of 164 grafts were analysed up to 500 days after transplantation. Of all transplants, 79.3% resulted in the formation of solid neural grafts. Grafted cells were identified by ‘H‐thymidine labelling and autoradiography’. Proliferation was studied by bromodeoxyuridine incorporation and decreased from an initial 35% at 1‐3 d after grafting to less than 1.6% after 40 days. The graft size was measured as a function of the embryonic age of the transplanted tissue. Our data indicate that telencephalic tissue harvested at embryonic day E 12.5 reproducibly yields large, fully differentiated neuroectodermal grafts. The parameters defined in this study will be useful for detailed analysis of neuroectodermal tissue from mice undergoing fatal neurodegeneration, such as knockout mice bearing lethal mutations.

Subarachnoid and intraventricular hemorrhage caused by hypernephroma metastasis, accompanied by innocent bilateral posterior communicating artery aneurysms

We present a case of subarachnoid and intraventricular hemorrhage due to an infratentorial metastasis of a renal cell carcinoma. The lesion was not apparent on initial magnetic resonance imaging (MRI) or in a follow-up examination (MRI and angiography) 6 weeks after the bleeding. The innocent bilateral posterior communicating artery aneurysms detected by cerebral angiography were treated surgically. The origin of the hemorrhage, however, remained unclear. Five months later, a surgically proven metastasis in the fourth ventricle subsequently gave the explanation for the bleeding.

Automatic Segmentation of the Cerebral Falx and Adjacent Gyri in 2D Ultrasound Images

We present an automatic segmentation of the cerebral falx and adjacent gyri (perifalcine region) for B-mode 2D ultrasound (US) images. The movement of brain tissue during neurosurgery reduces the accuracy of navigation systems which provide image guidance based on preoperative MRI (preMRI). Thus, the segmentation of the falx and its adjoining gyri in navigated, intraoperative US (iUS) may be used to im- prove navigation within preMRI scans by providing additional, spatially updated image information of the patients brain. The segmentation was tested on 50 2D US images and achieved on average a Dice coefficient of 0.79, a Hausdorff distance of 1.56 mm, and a Jaccard index of 0.64.