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Biomedical subjects

G Schackert

Publications and source records attributed to G Schackert.

At least 19 recordsLinked to original sources

Integration of intraoperative 3D-ultrasound in a commercial navigation system.

STUDY AIMS: The purpose of this study was the integration of three-dimensional ultrasound data into a neuronavigation system, in order to allow a guided intraoperative resection control during neurosurgical interventions. MATERIAL AND METHODS: A system for iterative neuronavigation based on 3D-ultrasound (US) has been developed. The main components of the system are the ultrasound device Voluson 730 (GE Healthcare) with a 5 - 9 MHz probe, the navigation system VectorVision2 (BrainLAB AG) and a standard PC with Windows XP. The ultrasound data are transferred via DICOM from the ultrasound device to an external computer, where they are processed with a C++ program for representation in the neuronavigation coordinate system. The data transfer between the navigation system and the external computer is performed via the VVLink interface from BrainLAB. The feasibility test of the system was performed with an ultrasound phantom RMI 403GS (Gammex-RMI GmbH). RESULTS: The error of homologous points mapping from US datasets to a CT dataset in the neuronavigation system was determined to be 1.9 +/- 0.97 mm. The maximum time required to technically integrate the ultrasound data into the navigation system was 1.5 min. CONCLUSIONS: The developed system allows 3D-ultrasound based navigation to be carried out with a commercially available navigation system. The functionality of this system has been proven by technical tests. Recording and integration of the ultrasound data can be repeated at any time during surgery and can be used to update anatomical data and consequently for resection control. Another application is the intraoperative adaptation of preoperative datasets (MRI or CT) in order to compensate for "brain shift" during neurosurgical operations.

Algorithms↗

Primary aspergillosis of the sphenoid sinus with pituitary invasion - a rare differential diagnosis of sellar lesions.

Aspergillosis belongs to the group of mycotic diseases of paranasal sinuses. The invasive forms, and particularly the fulminant forms, are potentially fatal. Isolated aspergillosis of the sphenoid sinus or the clivus is a difficult diagnosis, since the often misleading clinical manifestations of this rare disease develop late. These patients become apparent by neurological signs such as cavernous sinus syndrome, pseudotumor of the pituitary or the orbit. Diagnosis is often made intra-operatively or on histological examination. We report a case of invasive aspergillosis uniquely involving the sellar area revealed by clinical features suggesting a pseudotumor of the pituitary. Although such lesions are almost always seen in immune suppressed subjects, in our case, the patient was immune competent and had no past history of sinusitis.The question of whether, and when to perform limited or extensive surgery remains an issue for discussion, owing to the rarity of this disease honed by lack of experience. It depends on several factors: the kind of disease, the immunity, the subtype of invasive fungal sinusitis and the degree of tissue invasion.

Diagnosis, Differential↗

Outcomes of surgical resection of large solitary hemangioblastomas of the craniocervical junction with limitations in preoperative angiographic intervention: report of three cases.

INTRODUCTION: Hemangioblastomas of the central nervous system may occur sporadically, or in association with von Hippel-Lindau (vHL) disease. The treatment of large solitary hemangioblastomas of the posterior cranial fossa mandates a combination of angiographic intervention and surgery. However, large tumors may derive their vascularity from major cerebellar vessels, which can make their embolization hazardous. AIM: To describe the surgical outcomes of three cases of large hemangioblastomas with compression of the medulla oblongata, where the potential for preoperative embolization was extremely limited. CASES: Three patients (all males; 68, 36 and 38 years) presented with a history of chronic headache and caudal cranial nerve deficiencies. Diagnostic imaging showed large vascular lesions (4 x 3, 4 x 5 and 5 x 5 cm) at the craniocervical junction, compressing the brainstem. There were no concomitant findings associated with vHL disease. TREATMENT: Staged treatment was administered. Preoperative embolization was attempted at first. One patient (68 yrs) showed a PICA occlusion and associated cerebellar infarction after embolization; embolization was deemed hazardous in the other two. In the second phase, the lesions were removed via a midline suboccipital approach with resection of the arch of altas. Complete removal was possible in all three cases. POSTOPERATIVE COURSE AND FOLLOW-UP: The caudal cranial nerve deficiencies deteriorated soon after surgery in all three patients. A tracheotomy was required in two patients, which was removed uneventfully during the rehabilitation phase. Ventriculo-peritoneal shunts were implanted in two patients. MRI follow-up three (1 case) and four years (2 cases) after surgery showed no relapse. The Karnofsky Index scores were 80, 70 and 90 in the three patients aged 68, 36 and 38, respectively. CONCLUSION: Total microneurosurgical removal of large hemangioblastomas at the craniocervical junction with limited preoperative embolization (associated with morbidity) should be seriously considered. Although the early outcome is not encouraging, the long-term outcomes seem favorable.

Adult↗

The transaxillary approach in the treatment of thoracic outlet syndrome: a neurosurgical appraisal.

OBJECT: Different surgical approaches are available for the treatment of thoracic outlet syndrome (TOS). Our aim is to describe the transaxillary approach from a neurosurgical perspective, and to present the results in 15 patients. METHODS AND RESULTS: Fifteen patients (6 m and 9 f; mean age 44 yrs) were treated for neurogenic TOS. Four patients (26.7 %) demonstrated a cervical rib. The rest did not show a diagnosable bony anomaly (73.3 %). Provocative tests were neurologically positive in all patients (100 %); 4 patients additionally demonstrated vascular symptoms (26.7 %). Six patients demonstrated ulnar nerve F-wave latency (40 %). The transaxillary approach was used in all patients. In three patients with cervical ribs (20 %), an additional ventral approach was utilized. 14 patients remain symptom-free at a mean follow-up period of 24 months (93.4 %). One complained of pain recurrence at nine months after surgery and was treated conservatively (2(1/2) yrs). One patient developed pneumothorax after surgery (6.7 %). Four patients reported on numbness of the lateral thoracic wall, due to stretch injury of the intercostobrachial nerve that lies along the approach corridor (26.7 %). CONCLUSION: The transaxillary approach is one of several described surgical options for the treatment of TOS. It lies along a natural corridor and is non-muscle splitting. Although it requires a deep surgical corridor, the transaxillary approach allows definitive treatment of both bony and soft-tissue components causing TOS, provided the anatomical boundaries are recognized and respected. A persistent cervical rib, however, calls for an additional ventral approach. The complications are minimal and the results are predominantly acceptable.

Adult↗

Low-level microsatellite instability phenotype in sporadic glioblastoma multiforme.

PURPOSE: Genetic instability is a hallmark of glioblastoma multiforme (GBM). Microsatellite instability (MSI) is a significant event in the tumorigenesis of many sporadic malignancies. The aim of our investigation was to study microsatellite instability in newly diagnosed glioblastomas. METHODS: MSI was investigated in 109 GBMs with 15 microsatellite markers. Immunohistochemistry was performed for the mismatch repair (MMR) proteins hMLH1, hMSH2, hPMS2, and hMSH6 in cases showing MSI. Sequence and promoter methylation status of hMLH1 were analyzed in the case of a decreased hMLH1 protein expression as well. To further investigate MSI(+) GBMs we carried out studies of LOH at selected chromosome regions, EGFR amplification, and sequence of p53 and PTEN. RESULTS: MSI was observed in six GBMs (5.5%) and it was more frequent in GBMs with a previous lower grade astrocytoma (18.8% vs. 3.2%). MMR protein staining was positive in all MSI(+) GBMs except in one case, which showed an aberrant expression of hMLH1 and hPMS2 without hMLH1 inactivation. Among MSI(+) GBMs, one tumor corresponded to the GBM molecular type 1 (p53 mutation, no EGFR amplification), another tumor to type 2 (wild-type p53, EGFR amplification), and four tumors to neither type (wild-type p53, no EGFR amplification). None of the six tumors carried a PTEN mutation. CONCLUSIONS: MSI in GBM might be caused by inactivation of minor MMR genes rather than by a deficiency of hMLH1 or hMSH2 and it appears not to play a decisive role in the pathogenesis of these tumors. MSI(+) GBMs predominantly showed a profile which included wild-type of p53 and PTEN and absence of EGFR amplification but MSI occurred in all GBM molecular subtypes.

Adolescent↗

The diaphragma sellae meningioma -- a rare differential diagnosis of non-functioning pituitary adenoma.

It is important to differentiate the rare Diaphragma sellae meningioma from the quite common hormonally inactive pituitary adenoma, especially with regards to the surgical approach. The differentiation could, however, be problematic. We report the case of a 66-year-old woman with a Diaphragma sellae meningioma, which became apparent through a visual field and visual acuity disorder. Successful radical tumor extirpation was achieved via the transsphenoidal approach, since the space-occupying lesion was initially thought to be a hormonally inactive pituitary macroadenoma. However, histological investigation confirmed a meningioma. A careful retrospective analysis of the MRI revealed the possibility of a meningioma having been overlooked, since not all distinguishing features of this lesion were manifested. These criteria, as well as the principles of the surgical approach for treating sellar space-occupying lesions are discussed.

Adenoma↗

Prevention of brain metastasis formation by local expression of interleukin-4 or hemagglutinin antigen.

INTRODUCTION: Expression of hemagglutinin antigen of influenza virus (HA) by the murine colon carcinoma cell line (CT-26) produces systemic immunization against tumor challenges in the cecum, liver and lungs but not in the brain of BALB/c-mice. Immunization with IL-4 expressing CT-26 cells inhibits lung metastases formation. The purpose of our study was to examine the effects of HA or IL-4 expression on brain metastases formation. METHODS: Using selective internal carotid artery injections, brain metastases formation of HA or IL-4 expressing CT-26 cells with and without subcutaneous pre-immunization was evaluated in Balb/c mice. RESULTS: Systemic pre-immunization with HA or IL-4 expressing tumor cells cannot protect against brain metastases, while the local, intracerebral expression of HA or IL-4 inhibits the growth of hematogenous brain metastases. CONCLUSION: Pre-immunization with HA or IL-4 expressing tumor cells did produce systemic immunity against liver and lung metastases but not against brain metastases. Local, intracerebral expression of HA or IL-4 prevents from cerebral metastases formation in an animal model.

Animals↗

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

Adolescent↗

Comparison of functional brain PET images and intraoperative brain-mapping data using image-guided surgery.

OBJECTIVE: Knowledge about the spatial localization of eloquent brain areas is essential for resecting lesions in the vicinity of these areas. The classical approach is to perform surgery on the awake patient under local anesthesia using brain-mapping techniques. As an alternative, the location of eloquent areas can be visualized by preoperative functional brain-imaging techniques, for example, positron emission tomography (PET), functional magnetic resonance imaging (fMRI), or magnetoencephalography (MEG). Using functional activation PET, both methods were combined by integration into a frameless navigation system (BrainLAB) and used to map speech-eloquent areas. PATIENTS AND METHODS: Speech-eloquent areas were localized preoperatively in seven patients with a left-sided glioma using 2-[(18)F]-2-desoxy-D-glucose PET. Patients were scanned under silence conditions (i.e., with the patient remaining silent in a sound-proof cabin), and speech was activated using a verb-generation paradigm. The PET data were transferred to the neuronavigation workstation and matched with a preoperative 3D-MRI using an automatic image-fusion algorithm. Intraoperative speech localization was performed using brain-mapping techniques under local anesthesia with bipolar cortical stimulation. The stimulator position was mapped into the MRI/PET data set by neuronavigational tracking of the instrument. RESULTS: Functional PET images were integrated into the MRI-based neuronavigational system and could be transferred exactly to the operative field. By the additional integration of cortical stimulation, intraoperative electrophysiological findings can be directly compared with preoperative functional images. Seven patients with left-sided glioma were operated on using this protocol, confirming the technical feasibility. In three of seven patients, preoperative PET findings were not supported by intraoperative mapping. CONCLUSIONS: This matching and mapping technique is suitable for monitoring eloquent speech areas during surgical resection of extensive left-sided low-grade gliomas, allowing a direct comparison between intraoperative electrophysiological brain mapping and preoperative functional brain-imaging findings. The sensitivity and specificity of functional imaging techniques can now be evaluated by reconciling the data with the intraoperative stimulation results.

Adult↗

Surgery of brain metastases - pro and contra.

CONCLUSION: Surgery should be considered whenever possible. This means that the patient has to be in good clinical condition (Karnofsky performance score > 70), the extracerebral metastases should be stable, the number of cerebral lesions should not exceed more than 3 seedings, and the age of the patient should be below 70 years. Since brain metastases are usually well circumscribed, complete extirpation seems to be possible. Postoperative MRI should be demanded in order to confirm complete extirpation. Additional radiotherapy is indicated in case of subtotal resection of a single lesion and in multiple lesions. In single brain metastasis a prospective randomized trial is necessary to prove whether conventional radiotherapy is essential after surgery in the primary treatment of the tumors or can be delayed until cerebral lesions recur. Radiosurgery is an alternative to surgery in the treatment of metastasis.

Brain Neoplasms↗

Surgery of low-grade gliomas near speech-eloquent regions: brainmapping versus preoperative functional imaging.

The identification of eloquent areas is of utmost importance in the surgery of tumors located near speech-eloquent brain areas, since the classical concept of a constant localization was proven to be untrue and the spatial localization of these areas may show large interindividual differences. Some neurosurgical centers apply intraoperative electrophysiological methods that, however, necessitate the performance of surgery in the awake patient. This might be a severe burden both for the patient and the operating team in a procedure that lasts several hours; in addition, electrical stimulation may generate epileptic seizures. Alternatively, methods of functional brain imaging (e.g., PET, fMRI, MEG) may be applied, which allow individual localization of speech-eloquent areas. Matching of these image data with a conventional 3D-CT or MRI now allows the exact transfer of this information into the surgical field by neuronavigation. Whereas standards concerning electrophysiological stimulation techniques that could prevent a permanent postoperative worsening of language are available, until now it remains unclear whether the resection of regions shown to be active in functional brain imaging will cause a permanent postoperative deficit.

Brain Mapping↗

Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression.

Various radiotracers based on uracil nucleosides (e.g. [124I]2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil, [124I]FIAU) and acycloguanosine derivatives (e.g. [18F]9-[(3-fluoro-1-hydroxy-2-propoxy) methyl] guanine, [18F]FHPG) have been proposed for the non-invasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression. However, these radiotracers have been evaluated in different in vitro and in vivo models, precluding a direct comparison. Therefore, we directly compared [18F]FHPG and radioiodinated FIAU to assess their potential for PET imaging of transgene expression. The uptake of [125I]FIAU, [18F]FHPG and [3H]acyclovir was determined in vitro using four different HSV1-tk expressing cell lines and their respective negative controls. The in vitro tracer uptake was generally low in non-transduced parental cell lines. In HSV1-tk expressing cells, [3H]acyclovir showed approximately a twofold higher tracer accumulation, the [18F]FHPG uptake increased by about sixfold and the [125I]FIAU accumulation increased by about 28-fold after 120-min incubation of T1115 human glioblastoma cells. Similar results were found in the other cell lines. In addition, biodistribution and positron emission tomography (PET) studies with [18F]FHPG and [124/125I]FIAU were carried out in tumour-bearing BALB/c mice. Significantly higher specific accumulation of radioactivity was found for [125I]FIAU compared with [18F]FHPG. The ratio of specific tracer accumulation between [125I]FIAU and [18F]FHPG increased from 21 (30 min p.i.) to 119 (4 h p.i.). PET imaging, using [124I]FIAU, clearly visualised and delineated HSV1-tk expressing tumours, whereas only a negligible uptake of [18F]FHPG was observed. This study demonstrated that in vitro and in vivo, the radioiodinated uracil nucleoside FIAU has a significantly higher specific accumulation than the acycloguanosine derivative [18F]FHPG. This suggests that [124I]FIAU should be the preferred reporter probe for PET imaging of HSV1-tk gene expression. Thus, further attempts to develop suitable PET tracers for the assessment of HSV1-tk gene expression should also focus on 18F-labelled uracil derivatives.

Animals↗

Genesis of cerebral aneurysms--an update.

To elucidate the molecular pathogenesis of diseases has become a crucial step in the development of new treatment strategies. Although the pathogenesis of cerebral aneurysms has been studied intensively, it is poorly understood. Endogenous factors like elevated arterial blood pressure, the special anatomy of the Circle of Willis or the effect of haemodynamic factors, particularly originating at vessel bifurcation, are all known to be involved in the growth and rupture of an aneurysm. There is an ongoing discussion as to whether these factors also contribute to the very early steps of pathogenesis. Arteriosclerosis and secondary inflammatory reactions are thought to be elementary preconditions. Exogenous factors like cigarette smoking, heavy alcohol consumption or certain medications known to help generate arteriosclerosis and elevated blood pressure have also been found to be related to the occurrence of cerebral aneurysms. Furthermore, there has been a long-lasting debate on whether aneurysms might develop as a result of an inborn genetic defect. First-degree relatives of patients with cerebral aneurysms have a higher risk of having an aneurysm. In addition, the elevated prevalence of cerebral aneurysms in patients suffering from various inherited diseases points to a genetic background in the development of an aneurysm. Recent advances in molecular biology provide evidence that genetic variants of different candidate genes are associated with the occurrence of cerebral aneurysms. The aim of this review is to expose the current status of these various hypotheses and their contribution to the pathogenesis of cerebral aneurysms in order to provide a basis for future investigations in this field.

Aneurysm, Infected↗

Identification of uncommon chromosomal aberrations in the neuroglioma cell line H4 by spectral karyotyping.

To elucidate the reasons why mRNA expression of the LGI1 candidate tumor-suppressor gene was severely reduced in the glioma-derived cell line H4, as demonstrated in a previous study, we performed a cytogenetic analysis of this cell line using conventional methods and fluorescence in situ hybridization (FISH) techniques [spectral karyotyping (SKY), interphase- and chromosome FISH of metaphases (I- and C-FISH)]. Cell line H4 is monoclonal and near triploid (+/-3n). SKY enabled us to detect 24 structural aberrations: unbalanced translocations, n = 12; deletions, n = 10; insertion, n = 1; duplication, n = 1. The results were confirmed by I- and C-FISH analysis using chromosome-specific paints, centromer-specific probes and locus-specific probes for p53, PTEN/MMAC1, LGI1, Cyclin D1, EGR1, ETV6/TEL, AML1, and the genomic region 13q14.3 containing the Rb locus. We found loss of one copy of p53 as well as of one copy of Rb. Complete loss of PTEN/MMAC1 was detected, while all copies of LGI1 and Cyclin D1 were preserved. Interestingly, there was a gain of ETV6/TEL and EGR1, which were each present in quadruplicate. Additionally, the AML1 locus revealed mosaicism of cells with three and four copies, respectively. Additionally, a 5q-chromosome [del(5)(q13q33)] was found, which is one of the common features in hematological malignancies, and der(12)t(1;12) was found, suggesting that there might be an additional ETV6/TEL fusion protein. The combination of SKY, I- and C-FISH demonstrates that the neuroglioma cell line H4 harbors cytogenetic aberrations that are reported to occur in glioma-derived cell lines and additional chromosomal aberrations that have so far not been reported to occur in these cell lines. The complex aberrant karyotype and possibly generation of transcription factors by fusion proteins might be reasons for the impaired mRNA expression of the LGI1 candidate tumor-suppressor gene in cell line H4.

Adult↗

Albright's hereditary osteodystrophy associated with cerebellar pilocytic astrocytoma: coincidence or genetic relationship?

Albright's hereditary osteodystrophy (AHO) is a rare inherited disease characterized by skeletal abnormalities, short stature, and, in some cases, resistance to parathyroid hormone, resulting in pseudohypoparathyroidism (PHP). Heterozygous inactivating mutations of the GNAS1 gene are responsible for reduced activity of the alpha subunit of the Gs protein (G(Salpha)), a protein that mediates hormone signal transduction across cell membranes. G(salpha) is also known to have oncogenic potentials, leading to the development of human pituitary tumors and Leydig cell tumors. Here, we report the 1st case, a 3.5-year-old girl, with classic AHO phenotype and PHP type 1A associated with a cerebellar pilocytic astrocytoma. Coincidence or genetic relationships of both diseases are discussed according to molecular findings and current literature.

Adult↗