Introduction: Methods: Results: Conclusion:

1928 beschrieb Hugo Friedrich Kufs erstmalig eine Familie mit zerebralen, retinalen und kutanen Kavernomen. Mittlerweile wurden über 300 weitere Familien beschrieben. Ebenfalls wurden drei Genloci 7q21-q22 (mit dem Gen CCM1), 7p15-p13 (Gen CCM2) und 3q25.2-q27 (Gen CCM3) beschrieben, in denen Mutationen zu Kavernomen führen. Das Genprodukt von CCM1 ist das Protein Krit1 (Krev Interaction Trapped 1), das über verschiedene Mechanismen mit der Angiogenese interagiert. Das neu entdeckte CCM2-Gen enkodiert ein Protein, das möglicherweise eine dem Krit1 ähnliche Funktion in der Regulation der Angiogenese hat. Das CCM3-Gen wurde noch nicht beschrieben. In dieser Arbeit werden sowohl die klinischen und genetischen Befunde bei 15 deutschen Familien beschrieben.

The histological variability of Glioblastomas (GB) precludes the modern assimilation of theses tumors into a single histological tumor group. As an alternative to statistical histological evaluation, we investigated 1489 human GB in order to discover whether they could be correctly classified using Self-Organizing Maps (SOM). In all tumors 50 histological features, as well as the age and sex of the patients, were examined. Four clusters of GB with a significance of 52 (maximal significance 60) were found. Cluster C1 contained 37.47% of all GB and 41.09% of all polymorphic glioblastomas (PG). Cluster C2 included 35.06% of all GB and 44.96% of all giant cell glioblastomas (GCG). Cluster C3 contained 16.45% of all GB with a significant component of astroblasts, glioblasts and oligodendroglia. Cluster C4 included 11.01% of all GB, 87.80% of the gliosarcomas (GS) and 36.72% of all GCG. Placing a series of component windows with their maps side by side allows the immediate recognition of the dependencies on variables and the determination of variables necessary to build the specific clusters. The SOM allow a realistic histological classification, comparable to the actual classification by the WHO. In addition, we found new, small subclusters of human GB which may have a clinical significance. With SOM one can learn to discriminate, discard and delete data, select histological and clinical or genetic variables that are meaningful, and consequently influence the result of patient management.

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.

Purpose: To determine if the diffusion tensor imaging (DTI) parameters fractional anisotropy (FA) and mean diffusivity (MD) can differentiate between accompanying edema and tumor cell infiltration of white matter (WM) beyond the tumor edge as defined from conventional MRI in low- and high-grade gliomas. Materials and Methods: We examined 12 patients with high-grade gliomas/glioblastomas and eight patients with low-grade gliomas and compared them to 10 patients with meningiomas, in which no tumor infiltration is expected. The tumor was defined as the enhancing area in glioblastomas and meningiomas and as the area of increased T2-signal in low-grade gliomas. FA and MD were measured in the center of the tumor and in the adjacent WM. The contralateral WM and internal capsule were used as an internal standard. Results: Comparing the WM areas of increased T2-signal adjacent to meningiomas and glioblastomas, we saw a trend (without significance) towards a reduction of FA, but not of MD, in glioblastomas. We found no changes of FA and MD in the WM adjacent to low-grade gliomas (without T2-signal increase) compared to the WM of the contralateral hemisphere. In meningiomas and high-grade gliomas/ glioblastomas, a narrow rim of significantly (P < 0.01) increased FA and decreased MD values around the enhancing tumor area was seen, whereas in low-grade gliomas, such a rim could not be defined. There was no contribution of FA or MD to grading of gliomas. Conclusion: In glioblastomas, a reduction of FA in the edematous area. surrounding the tumor may indicate tumor cell infiltration, but a reliable differentiation between infiltration and vasogenic edema is not yet possible on the basis of DTI. The additional finding of a narrow rim of increased FA and decreased MD at the edge of glioblastomas (as well as in meningiomas) may be caused by compressed WM fibers and/or increased vascularity, but does not contribute to exclude peripheral cellular infiltration. (C) 2004 Wiley-Liss, Inc.

OBJECTIVE:Endoscopic third ventriculostomy (ETV) is an effective treatment for occlusive hydrocephalus caused by an obstruction of the CSF flow in the aqueduct or the posterior fossa. We evaluated the factors age, pathology and surgical technique on the results of the ETV.METHODS:Between November 1992 and October 2000 171 ETV have been performed in 159 patients. The follow-up was evaluated in 150 patients. The age ranged from 10 days to 77 years (mean age 35 years). The hydrocephalus was caused by benign aqueductal stenosis in 77 patients, space-occupying lesions in 59, by intraventricular hemorrhages in 11, and by other causes in 3 patients. The trajectory was planned in 31 patients by frame-based and in 4 patients by frameless stereotaxy.RESULTS:The overall success rate of a single ETV was 71.3 % and including successful re-ETV 76.7 %. Best results were observed in adults and children older than 1 year. Infants demonstrated significantly worser outcomes. Patients with benign aqueductal stenosis and tumor compressing the aqueduct had the greatest profit from the ETV. The stereotactic guidance had no influence on the outcome and the number of severe complications. Complications were one arterial bleeding, three venous bleedings, and one ICB, all without permanent deficit, except one permanent hemiparesis. No mortality was observed.

In this article, 12 re-ventriculostomies in the treatment for obstructive hydrocephalus are described. The etiology of the hydrocephalus was a benign aqueductal stenosis in 9 patients, a tumor around the aqueduct in 2 patients and intraventricular bleeding in one patient. In all cases the initial ventriculostomy was successful, but after a time interval of 2 weeks to 6 years the patients developed similar clinical symptoms as preoperatively. In all except one case the radiological findings spoke in favour of stoma closure. Intraoperatively the stoma was completely closed in 9 patients and in 3 patients a subtotal closure was observed. In all cases a re-ventriculostomy was performed bluntly with a Fogarty catheter in loco typico at the floor of the third ventricle. Of the 12 patients 6 had an excellent outcome postoperatively, one patient improved and one had a benefit from the re-ventriculostomy although he died of cardiac problems. In the remaining 4 patients the re-ventriculostomy was not successful and the patients needed a shunt operation. In conclusion, after initially successful endoscopic third ventriculostomy, re-ventriculostomy should be considered as a sufficient treatment option in case of suspected stoma dysfunction.

Frame-based stereotactic biopsies are time-consuming procedures making necessary head fixation in a ring, explicit coordinate calculation and setting of the parameters. Frameless systems make many of these intermediate steps unnecessary, impose less mechanical restrictions regarding access to the lesions, and with slight modifications can be used to perform stereotactic biopsies. A special adaptation designed to fix the holder and the biopsy instrument is described. The neuronavigation optical tracking system of Radionics was used. CT scans were performed with 6 skin markers. Calibration was performed after head fixation in the Mayfield clamp. Mean calibration error was 2.19 +/- 0.81 mm. The light-emitting diode holder of the pointer was fixed into 2 Leila arms and moved under visual control based on CT images. The target point was selected, Leila arms fixed and a burr hole performed. The cannula was introduced to the target, being fitted with a depth stop in a length identical to that of the pointer on the screen. If necessary a second trajectory was easily selected. 49 patients underwent a frameless stereotactic biopsy. All targets except seven were superficial or in the white matter. In selected cases the biopsies were taken from deep-seated lesions. A histological diagnosis was obtained in 100% of the cases. Four cases deteriorated postoperatively, two of these related to intratumoral bleeding. Navigation is a simple and effective method to perform biopsies of superficial and relatively large lesions. Frame-based procedures are restricted to brainstem tumors and lesions less than 1.5 cm in diameter.

Computed tomography (CT) images in combination with a navigation device enable three-dimensional (3-D) localization of intracranial lesions. Furthermore, CT scanning can be adapted for intraoperative application to actualize the image data and to check the anatomical situation during the operation. Frameless navigation was used in 100 patients. The procedure was performed in 46 cases with an optical navigation system, in 38 cases with a sensory arm, and in 16 cases with a navigated microscope. Six skin markers were used for registration. Mean fiducial registration error was 2.18 mm with a standard deviation of 1.03 mm. The indication for navigation was tumor localization and planning of the craniotomy in 81 cases, stereotactic biopsy in eight cases, and endoscopic procedures in 11 cases. Technical problems with the navigation system were observed in nine cases. In two additional cases the tumor was not found by navigation. All eight biopsy cases were successful, and histologically relevant specimens were obtained without complications. Navigation was helpful in 11 endoscopic cases for choosing an optimal trajectory through the foramen of Monro or for connecting multiple intraventricular cysts. For intraoperative CT imaging, the mobile Philips Tomoscan M was adapted to the needs of the operating environment. The mobile CT was used in 78 cases in the operating room: 16 patients who underwent a stereotactic procedure had only preoperative CT scans, 36 patients had an intraoperative CT during tumor surgery, and 26 patients during the test period of the device had only a postoperative CT investigation. In 10 cases (28%) of the intraoperative group the remaining tumor tissue could be demonstrated on the CT scans. The tumor remnants that were not visible in the microscopical surgical field were subsequently removed. According to our results, intraoperative navigation seems superior for the localization of intracranial lesions and intraoperative CT is more useful when considering the radicality of tumor removal.

Stereotactic guidance is useful for planning an accurate trajectory to the third ventricle, A guiding block with a ball joint was developed for frame-based endoscopy and adaptors for arm-based and armless navigation systems. Between 1992 and 1996, 52 patients were operated on endoscopically in the third ventricle under stereotactic guidance. Thirty-eight ventriculostomies, 13 biopsies and 10 cystic lesions were performed, The coordinates of two points were calculated; one in the foramen of Monro and the second in the third ventricle, The ventriculostomy was performed under endoscopic control bluntly with a Fogarty catheter in front of the basilar artery. Twenty-seven (71%) of the patients had a long-lasting benefit from the operation, 6 (16%) had no benefit, and in 5 (13%) a shunt operation was necessary, Poor outcome was due to closure of the stoma by tumor growth or infection. Three cysts were fenestrated and 7 colloid cysts partly evacuated. One incident of bleeding occurred in the frontal lobe in the path of the endoscope which was treated conservatively with success. Transient memory deficit was noted in one patient and double vision in the second.

To evaluate the usefulness of transendoscopic sonography we studied two new sono probes of 6F diameter in 17 fresh specimens. We saw a precise imaging of well known anatomical structures and moreover got a additional dimension in endoscopy, as the sono adds to the endo view a transversal scan like a mini CT at the tip of the probe. By that we also experienced the navigation characteristic of this imaging technique, both in real time and on line. Some 3-D reconstructions of the ventricles are examinated. First clinical use has been done and adaptation of the equipment to neurosurgery is necessary.