Jürgen Meixensberger

Publications (79)131.29 Total impact

• Article: Evaluation of a semi-automatic segmentation algorithm in 3D intraoperative ultrasound brain angiography.

  Claire Chalopin, Karl Krissian, Jürgen Meixensberger, Andrea Müns, Felix Arlt, Dirk Lindner
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  ABSTRACT: Abstract In this work, we adapted a semi-automatic segmentation algorithm for vascular structures to extract cerebral blood vessels in the 3D intraoperative contrast-enhanced ultrasound angiographic (3D-iUSA) data of the brain. We quantitatively evaluated the segmentation method with a physical vascular phantom. The geometrical features of the segmentation model generated by the algorithm were compared with the theoretical tube values and manual delineations provided by observers. For a silicon tube with a radius of 2 mm, the results showed that the algorithm overestimated the lumen radii values by about 1 mm, representing one voxel in the 3D-iUSA data. However, the observers were more hindered by noise and artifacts in the data, resulting in a larger overestimation of the tube lumen (twice the reference size). The first results on 3D-iUSA patient data showed that the algorithm could correctly restitute the main vascular segments with realistic geometrical features data, despite noise, artifacts and unclear blood vessel borders. A future aim of this work is to provide neurosurgeons with a visualization tool to navigate through the brain during aneurysm clipping operations.
  Biomedizinische Technik/Biomedical Engineering 05/2013; · 0.53 Impact Factor
• Article: The impact of missing sensor information on surgical workflow management.

  Philipp Liebmann, Jürgen Meixensberger, Peter Wiedemann, Thomas Neumuth
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  ABSTRACT: OBJECTIVE: Sensor systems in the operating room may encounter intermittent data losses that reduce the performance of surgical workflow management systems (SWFMS). Sensor data loss could impact SWFMS-based decision support, device parameterization, and information presentation. The purpose of this study was to understand the robustness of surgical process models when sensor information is partially missing. SWFMS changes caused by wrong or no data from the sensor system which tracks the progress of a surgical intervention were tested. MATERIALS AND METHODS: The individual surgical process models (iSPMs) from 100 different cataract procedures of 3 ophthalmologic surgeons were used to select a randomized subset and create a generalized surgical process model (gSPM). A disjoint subset was selected from the iSPMs and used to simulate the surgical process against the gSPM. The loss of sensor data was simulated by removing some information from one task in the iSPM. The effect of missing sensor data was measured using several metrics: (a) successful relocation of the path in the gSPM, (b) the number of steps to find the converging point, and (c) the perspective with the highest occurrence of unsuccessful path findings. RESULTS: A gSPM built using 30 % of the iSPMs successfully found the correct path in 90 % of the cases. The most critical sensor data were the information regarding the instrument used by the surgeon. CONCLUSION: We found that use of a gSPM to provide input data for a SWFMS is robust and can be accurate despite missing sensor data. A surgical workflow management system can provide the surgeon with workflow guidance in the OR for most cases. Sensor systems for surgical process tracking can be evaluated based on the stability and accuracy of functional and spatial operative results.
  International Journal of Computer Assisted Radiology and Surgery 03/2013; · 1.48 Impact Factor
• Article: Impact of 5-lipoxygenase inhibitors on the spatiotemporal distribution of inflammatory cells and neuronal COX-2 expression following experimental traumatic brain injury in rats.

  Wolfgang Härtig, Dominik Michalski, Gudrun Seeger, Cornelia Voigt, Cornelius K Donat, Julia Dulin, Johannes Kacza, Jürgen Meixensberger, Thomas Arendt, Martin U Schuhmann
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  ABSTRACT: The inflammatory response following traumatic brain injury (TBI) contributes to neuronal death with poor outcome. Although anti-inflammatory strategies were beneficial in experimental TBI, clinical translations mostly failed, probably caused by the complexity of involved cells and mediators. We recently showed in a rat model of controlled cortical impact (CCI) that leukotriene inhibitors (LIs) attenuate contusion growth and improve neuronal survival. This study focuses on spatiotemporal characteristics of macrophages and granulocytes, typically involved in inflammatory processes, and neuronal COX-2 expression. Effects of treatment with LIs (Boscari/MK-886), started prior trauma, were evaluated by quantifying CD68(+), CD43(+) and COX-2(+) cells 24h and 72h post-CCI in the parietal cortex (PC), CA3 region, dentate gyrus (DG) and visual/auditory cortex (v/aC). Correlations were applied to identify inter-cellular relationships. At 24h, untreated animals showed granulocyte invasion in all regions, decreasing towards 72h. Macrophages increased from 24h to 72h post-CCI in PC and v/aC. COX-2(+) neurones showed no temporal changes, except of an increase in the CA3 region at 72h. Treatment reduced granulocytes at 24h in the pericontusional zone and hippocampus, and macrophages at 72h in the PC and v/aC. COX-2 expression remained unaffected by LIs, except of time-specific changes in the DG (increase/decrease at 24/72h). Interrelations confirmed concomitant cellular reactions beyond the initial trauma site. In conclusion, LIs attenuated the cellular inflammatory response following CCI. Future studies have to clarify region-specific effects and explore the potential of a clinically more relevant therapeutic approach applying LIs after CCI.
  Brain research 12/2012; · 2.46 Impact Factor
• Article: Does histology predict the clinical outcome after lumbar intervertebral disc herniation: No.

  Dirk Winkler, Niels Hammer, Johannes Gossner, Ralf Schober, Heinz-Ekkehard Vitzthum, Jürgen Meixensberger
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  ABSTRACT: BACKGROUND AND OBJECTIVES: The histological analysis of extirpated intervertebral disc material from patients undergoing discectomy due to lumbar disc herniation remains an established procedure. In looking at whether the high costs that histological examination entails can be justified, it is worthwhile to ascertain the actual diagnostic benefit of this procedure. The aim of this study was to address the following hypothesis: Do histological characteristics such as the presence of inflammatory cells (macrophages) predict the clinical outcome of patients undergoing discectomy? MATERIALS AND METHODS: A total of 343 patients (221 males, 122 females, mean age 44.7years) were treated microsurgically by root decompression subsequent to interlaminar fenestration. The patient history, the operated disc segment, the radicular and vegetative symptoms as well as the early and long-term outcome were evaluated. The excised disc material was classified histologically. CD68 staining was performed in 11 randomly chosen patients with good and in 11 patients with poor subjective long-term outcome for quantitative evaluation of macrophage count. RESULTS: The follow up rate was 69.7%. Three hundred and five patients underwent disc surgery for the first time and 38 patients underwent relapse disc surgery. Moderate, pronounced and severe degeneration was found in 16, 231 and 92 patients, respectively. Positive subjective assessment of early outcome was 91% and 92% for the primary and relapse group, whereas long-term outcome was positive in 69% and 50% for the primary and the relapse group respectively. No histological features including CD68 (macrophage) count showed statistically significant correlations with the success of clinical treatment. DISCUSSION AND CONCLUSIONS: A reliable prediction of the success of treatment, including patient outcome, cannot be made on the basis of the present histological criteria. The hypothesis must therefore be rejected.
  Medical Hypotheses 12/2012; · 1.39 Impact Factor
• Article: Operative management of idiopathic spinal intradural arachnoid cysts in children: a systematic review.

  Petros Evangelou, Jürgen Meixensberger, Matthias Bernhard, Wolfgang Hirsch, Wieland Kiess, Andreas Merkenschlager, Ulf Nestler, Matthias Preuss
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  ABSTRACT: BACKGROUND: Spinal intradural arachnoid cysts are rare with only a few patients reported so far. Idiopathic, traumatic, posthemorrhagic, and postinflammatory causes have been reported in the literature. Especially, idiopathic lesions, in which other possible etiological factors have been ruled out, seem to be rare. PATIENTS AND METHODS: We systematically reviewed the literature in regards to localization within the spinal canal, treatment options, complications, and outcome. Additionally, we present management strategies in two progressively symptomatic children less than 3 years of age with idiopathic intradural arachnoid cysts. RESULTS: In total, 21 pediatric cases including the presented cases have been analyzed. Anterior idiopathic spinal arachnoid cysts are predominantly located in the cervical spine in 87.5 % of all cases, whereas posterior cysts can be found at thoracic and thoracolumbar segments in 84.6 % of the patients. Most children presented with motor deficits (76.2 %). Twenty-five percent of anterior spinal arachnoid cysts caused back pain as the only presenting symptom. Open fenestration by a dorsal approach has been used in the vast majority of cases. No major surgical complications have been reported. Ninety-four percent of all patients did improve or showed no neurological deficits. Recurrence rate after successful surgical treatment was low (9.5 %). CONCLUSION: Idiopathic spinal intradural arachnoid cysts can present with neurological deficits in children. Pathologies are predominantly located in the cervical spine anteriorly and in thoracic and thoracolumbar segments posteriorly to the spinal cord. In symptomatic cases, microsurgical excision and cyst wall fenestration via laminotomy are recommended. Our radiological, intraoperative, and pathological findings support the cerebrospinal fluid obstruction and vent mechanism theory of arachnoid cysts.
  Child s Nervous System 12/2012; · 1.54 Impact Factor
• Article: Intervention time prediction from surgical low-level tasks.

  Stefan Franke, Jürgen Meixensberger, Thomas Neumuth
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  ABSTRACT: OBJECTIVE: Effective time and resource management in the operating room requires process information concerning the surgical procedure being performed. A major parameter relevant to the intraoperative process is the remaining intervention time. The work presented here describes an approach for the prediction of the remaining intervention time based on surgical low-level tasks. MATERIALS AND METHODS: A surgical process model optimized for time prediction was designed together with a prediction algorithm. The prediction accuracy was evaluated for two different neurosurgical interventions: discectomy and brain tumor resections. A repeated random sub-sampling validation study was conducted based on 20 recorded discectomies and 40 brain tumor resections. RESULTS: The mean absolute error of the remaining intervention time predictions was 13 min 24 s for discectomies and 29 min 20 s for brain tumor removals. The error decreases as the intervention progresses. DISCUSSION: The approach discussed allows for the on-line prediction of the remaining intervention time based on intraoperative information. The method is able to handle demanding and variable surgical procedures, such as brain tumor resections. A randomized study showed that prediction accuracies are reasonable for various clinical applications. CONCLUSION: The predictions can be used by the OR staff, the technical infrastructure of the OR, and centralized management. The predictions also support intervention scheduling and resource management when resources are shared among different operating rooms, thereby reducing resource conflicts. The predictions could also contribute to the improvement of surgical workflow and patient care.
  Journal of Biomedical Informatics 10/2012; · 1.79 Impact Factor
• Article: Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage.

  Matthias Jaeger, Martin Soehle, Martin U Schuhmann, Jürgen Meixensberger
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  ABSTRACT: The purpose of this study was to investigate the relationship between cerebrovascular autoregulation and outcome after aneurysmal subarachnoid hemorrhage. In a prospective observational study, 80 patients after severe subarachnoid hemorrhage were continuously monitored for cerebral perfusion pressure and partial pressure of brain tissue oxygen for an average of 7.9 days (range, 1.9-14.9 days). Autoregulation was assessed using the index of brain tissue oxygen pressure reactivity (ORx), a moving correlation coefficient between cerebral perfusion pressure and partial pressure of brain tissue oxygen. High ORx indicates impaired autoregulation; low ORx signifies intact autoregulation. Outcome was determined at 6 months and dichotomized into favorable (Glasgow Outcome Scale 4-5) and unfavorable outcome (Glasgow Outcome Scale 1-3). Twenty-four patients had a favorable and 56 an unfavorable outcome. In a univariate analysis, there were significant differences in autoregulation (ORx 0.19±0.10 versus 0.37±0.11, P<0.001, for favorable versus unfavorable outcome, respectively), age (44.1±11.0 years versus 54.2±12.1 years, P=0.001), occurrence of delayed cerebral infarction (8% versus 46%, P<0.001), use of coiling (25% versus 54%, P=0.02), partial pressure of brain tissue oxygen (24.9±6.6 mm Hg versus 21.8±6.3 mm Hg, P=0.048), and Fisher grade (P=0.03). In a multivariate analysis, ORx (P<0.001) and age (P=0.003) retained an independent predictive value for outcome. ORx correlated with Glasgow Outcome Scale (r=-0.70, P<0.001). The status of cerebrovascular autoregulation might be an important pathophysiological factor in the disease process after subarachnoid hemorrhage, because impaired autoregulation was independently associated with an unfavorable outcome.
  Stroke 05/2012; 43(8):2097-101. · 5.73 Impact Factor
• Article: Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial.

  Wolfgang Wick, Michael Platten, Christoph Meisner, Jörg Felsberg, Ghazaleh Tabatabai, Matthias Simon, Guido Nikkhah, Kirsten Papsdorf, Joachim P Steinbach, Michael Sabel, Stephanie E Combs, Jan Vesper, Christian Braun, Jürgen Meixensberger, Ralf Ketter, Regine Mayer-Steinacker, Guido Reifenberger, Michael Weller
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  ABSTRACT: Radiotherapy is the standard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined. We did a randomised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma. Between May 15, 2005, and Nov 2, 2009, we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65 years, and a Karnofsky performance score of 60 or higher. Patients were randomly assigned 100 mg/m(2) temozolomide, given on days 1-7 of 1 week on, 1 week off cycles, or radiotherapy of 60·0 Gy, administered over 6-7 weeks in 30 fractions of 1·8-2·0 Gy. The primary endpoint was overall survival. We assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01502241. Of 584 patients screened, we enrolled 412. 373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses. Median overall survival was 8·6 months (95% CI 7·3-10·2) in the temozolomide group versus 9·6 months (8·2-10·8) in the radiotherapy group (hazard ratio [HR] 1·09, 95% CI 0·84-1·42, p(non-inferiority)=0·033). Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3·3 months [95% CI 3·2-4·1] vs 4·7 [4·2-5·2]; HR 1·15, 95% CI 0·92-1·43, p(non-inferiority)=0·043). Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested. MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11·9 months [95% CI 9·0 to not reached] vs 8·2 months [7·0-10·0]; HR 0·62, 95% CI 0·42-0·91, p=0·014). EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8·4 months [95e% CI 5·5-11·7] vs 4·6 [4·2-5·0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3·3 months [3·0-3·5] vs 4·6 months [3·7-6·3]). The most frequent grade 3-4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight). Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making. Merck Sharp & Dohme.
  The lancet oncology 05/2012; 13(7):707-15. · 14.47 Impact Factor
• Article: Detection of novel genomic aberrations in anaplastic astrocytomas by GTG-banding, SKY, locus-specific FISH, and high density SNP-array.

  Heidrun Holland, Peter Ahnert, Ronald Koschny, Holger Kirsten, Manfred Bauer, Ralf Schober, Jürgen Meixensberger, Dominik Fritzsch, Wolfgang Krupp
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  ABSTRACT: Astrocytomas represent the largest and most common subgroup of brain tumors. Anaplastic astrocytoma (WHO grade III) may arise from low-grade diffuse astrocytoma (WHO grade II) or as primary tumors without any precursor lesion. Comprehensive analyses of anaplastic astrocytomas combining both cytogenetic and molecular cytogenetic techniques are rare. Therefore, we analyzed genomic alterations of five anaplastic astrocytomas using high-density single nucleotide polymorphism arrays combined with GTG-banding and FISH-techniques. By cytogenetics, we found 169 structural chromosomal aberrations most frequently involving chromosomes 1, 2, 3, 4, 10, and 12, including two not previously described alterations, a nonreciprocal translocation t(3;11)(p12;q13), and one interstitial chromosomal deletion del(2)(q21q31). Additionally, we detected previously not documented loss of heterozygosity (LOH) without copy number changes in 4/5 anaplastic astrocytomas on chromosome regions 5q11.2, 5q22.1, 6q21, 7q21.11, 7q31.33, 8q11.22, 14q21.1, 17q21.31, and 17q22, suggesting segmental uniparental disomy (UPD), applying high-density single nucleotide polymorphism arrays. UPDs are currently considered to play an important role in the initiation and progression of different malignancies. The significance of previously not described genetic alterations in anaplastic astrocytomas presented here needs to be confirmed in a larger series.
  Pathology - Research and Practice 05/2012; 208(6):325-30. · 1.21 Impact Factor
• Article: Hedgehog signaling in glioblastoma multiforme.

  Stefanie Braun, Henry Oppermann, Antje Mueller, Christof Renner, Amalya Hovhannisyan, Rainer Baran-Schmidt, Rolf Gebhardt, Alan Hipkiss, Joachim Thiery, Jürgen Meixensberger, Frank Gaunitz
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  ABSTRACT: Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults with a median survival of 14.6 mo under the best available treatment. New treatment strategies are therefore urgently required, for which a profound understanding of tumor biology is necessary. Much effort has been devoted to tumor-specific aberrant signaling processes. Recently it was discovered that the transcription factor Gli1, which is activated by hedgehog signaling, is a highly predictive marker in GBM, as determined by immunohistochemistry. To determine whether GBM cells have transcriptionally active Gli1, we performed experiments with reporter genes with cells isolated from surgically removed human tumors and cell lines. We also determined whether the hedgehog signaling inhibitor cyclopamine influences reporter gene expression and cell viability, and we determined the expression of Gli1, SHH and Patched1 by quantitative real-time RT-PCR. Reporter gene analysis of nine cultures and four cell lines demonstrated a significantly enhanced transcriptional activity in six tumor cell cultures and all cell lines. Analysis of cell viability in the presence of cyclopamine revealed a response of all cell cultures with the exception of one primary culture and one cell line, but only one cell line responded to cyclopamine with reduced hedgehog signaling activity. This indicates that the toxicity of cyclopamine toward GBM cells is independent from hedgehog signaling. Since no correlation between hedgehog activity and SHH, Gli1 and Patched1 mRNA levels was observed we conclude that other mechanisms aside from transcriptional regulation of these factors are responsible for hedgehog activity in tumor cells derived from GBM.
  Cancer biology & therapy 05/2012; 13(7):487-95. · 2.64 Impact Factor
• Article: MicroTargeting® platform: an individual stereotaxic device in functional neurosurgery

  Dirk Winkler, Gero Strauss, Jochen Helm, Axel Goldammer, Jens-Peter Schneider, Johannes Schwarz, Jürgen Meixensberger
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  ABSTRACT: Object: Deep brain stimulation of the Nucleus subthalamicus (DBS-STN) results in an improvement of cardinal symptoms of Parkinson disease (PD) and allows a significant reduction of medication. Because of the potential risk of inaccuracies during image acquisition, planning procedure, placement of test electrodes and final electrode insertion a microTargeting® platform, FHC Company, Germany, as an example of automation in stereotaxic neurosurgery was used. Materials and methods: A 65-years-old male patient with PD with severe motor dysfunctions was selected for DBS-STN. Preoperatively and just before image acquisition (CT, T1w-, T2w-MRI) three WayPointTM anchors per side were implanted in the skull for further definition of entry and target points, postprocessing and for creation of an individual stereotaxic platform, which was fixed with the patient’s head intraoperatively. Results: The “MicroTargeting” system allowed a precise detection of the STN and definition of electrode trajectories, which was confirmed intraoperatively by microelectrode recording and macrostimulation. At a frequency of 130Hz, 1.5mA and 60μ s pulse width the typical motor dysfunction disappeared and no stimulation associated side effects could be registered. Adjustment and reduction of medication followed. Conclusion: MicroTargeting® platform replaced traditional target arch and electrode positioning system in an excellent way and increased the patient’s comfort. With the individual stereotaxic platform an example for automation was found, which has the potential to increase the patient’s and neurosurgeon’s safety.
  International Journal of Computer Assisted Radiology and Surgery 04/2012; 1(5):295-299. · 1.48 Impact Factor
• Article: Carnosine Inhibits Growth of Cells Isolated from Human Glioblastoma Multiforme

  Christof Renner, Anne Seyffarth, Susana Garcia de Arriba, Jürgen Meixensberger, Rolf Gebhardt, Frank Gaunitz
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  ABSTRACT: The present study evaluates the effect of the naturally occurring dipeptide carnosine on primary cell cultures established from patients with glioblastoma multiforme. Surgically removed tumors were used to establish primary cell cultures that were incubated for 96h with medium supplemented with carnosine at concentrations of 20, 40 and 50mM. Following incubation, dehydrogenase activity, cellular adenosine triphosphate concentration (ATP), caspase activity, lactate dehydrogenase (LDH) release and the rate of DNA synthesis were determined. After 96h of carnosine treatment a significant reduction in cellular ATP and dehydrogenase activity was detected already at a concentration of 20mM carnosine. Carnosine (50mM) reduced ATP concentration to 42.7±13.5% (n=6) and dehydrogenase activity to 41.0±19.3% (n=6) compared to untreated cells. Additional experiments revealed no sign of enhanced apoptosis or necrosis in the presence of carnosine. However, a quantitative bromo-desoxy-uridine-based proliferation assay demonstrated a clear effect of carnosine on DNA synthesis reducing its rate down to 50% (2cultures) and 10% (4cultures). Therefore, it can be concluded that carnosine is obviously able to inhibit proliferation of cells derived from glioblastoma. Since it is a naturally occurring substance that appears to be non-toxic to normal tissue and is able to penetrate the blood–brain barrier it may be a candidate for a therapeutic agent that may reduce proliferation of neoplastic cells even invivo and especially in cases of glioblastoma multiforme.
  International Journal of Peptide Research and Therapeutics 04/2012; 14(2):127-135. · 0.99 Impact Factor
• Source

  Available from: PubMed Central

  Article: Giant intradiploic epidermoid cyst with large osteolytic lesions of the skull: a case report.

  Wolfgang Krupp, Alexander Heckert, Heidrun Holland, Jürgen Meixensberger, Dominik Fritzsch
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  ABSTRACT: We report a case of tumor growth over a period of four decades, presenting with large multicentric lytic lesions of the skull and a profound mass effect, without neurological deficits. Clinical and radiological features of a patient with a giant intradiploic epidermoid and its impact on the choice of treatments are discussed. An 81-year-old Caucasian man, who had first noticed a painless subcutaneous swelling over the left frontal scalp about 40 years ago, presented after a short episode of dizziness, which he experienced after treatment of focal retinal detachment. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations revealed an exceptionally large tumor involving major parts of the skull with extensive destruction of the bone and distinct deformation of the brain. Considering his age and the absence of neurological deficits or pain, the patient refused the option of tumor removal and cranioplasty, yet agreed to a biopsy, which confirmed the suspected diagnosis. The course of the disease demonstrates that even patients with large tumors, inducing distinct pathomorphological changes, do not necessarily experience significant impairment of their quality of life without surgery. This is an impressive example of the chance to lead a long and satisfying life without specific medical treatment, avoiding the inherent risks of these procedures. Yet, there is a clear indication for surgery of intradiploic epidermoids in most cases described in the literature.
  Journal of Medical Case Reports 03/2012; 6(1):85.
• Article: High resolution genomic profiling and classical cytogenetics in a group of benign and atypical meningiomas.

  Heidrun Holland, Kristin Mocker, Peter Ahnert, Holger Kirsten, Helene Hantmann, Ronald Koschny, Manfred Bauer, Ralf Schober, Markus Scholz, Jürgen Meixensberger, Wolfgang Krupp
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  ABSTRACT: Meningiomas are classified as benign, atypical, or anaplastic. The majority are sporadic, solitary, and benign tumors with favorable prognoses. However, the prognosis for patients with anaplastic meningiomas remains less favorable. High resolution genomic profiling has the capacity to provide more detailed information. Therefore, we analyzed genomic aberrations of benign and atypical meningiomas using single nucleotide polymorphism (SNP) array, combined with G-banding by trypsin using Giemsa stain (GTG banding), spectral karyotyping, and locus-specific fluorescence in situ hybridization (FISH). We confirmed frequently detected chromosomal aberrations in meningiomas and identified novel genetic events. Applying SNP array, we identified constitutional de novo loss or gain within chromosome 22 in three patients, possibly representing inherited causal events for meningioma formation. We show evidence for somatic segmental uniparental disomy in regions 4p16.1, 7q31.2, 8p23.2, and 9p22.1 not previously described for primary meningioma. GTG-banding and spectral karyotyping detected a novel balanced reciprocal translocation t(4;10)(q12;q26) in one benign meningioma. A paracentric inversion within 1p36, previously described as novel, was detected as a recurrent chromosomal aberration in benign and atypical meningiomas. Analyses of tumors and matched normal tissues with a combination of SNP arrays and complementary techniques will help to further elucidate potentially causal genetic events for tumorigenesis of meningioma.
  Cancer Genetics 10/2011; 204(10):541-9.
• Article: Search for genetic variants in the ryanodine receptor 1 gene in patients with symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

  Henrik Rueffert, Anja Gumplinger, Christof Renner, Markus Dengl, Andreas Reske, Udo X Kaisers, Jürgen Meixensberger
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  ABSTRACT: Cerebral vasospasm is one of the most serious complications after subarachnoid hemorrhage (SAH). The cerebral artery diameter is regulated by complex physiological mechanisms. Among them the regulation of intracellular calcium homeostasis seems to play a crucial role. Recent data suggest that ryanodine receptors (RYRs) are involved in regulating the luminal calcium concentration in vascular smooth muscle cells. In this gene association investigation, we studied the question as to whether variants in the gene for the ryanodine receptors subtype 1 (RYR1) are associated with symptomatic cerebral vasospasm following SAH. After informed consent genomic DNA analysis was performed from a whole blood sample in 46 patients suffering from aneurysmal SAH. 16 Patients were affected by symptomatic vasospasm. The RYR1 gene was screened for possible genetic variants by means of direct sequencing. The association of these variants was correlated to the development of symptomatic vasospasm, which was confirmed by clinical examination combined with cerebral angiography, transcranial doppler sonography, or CT scan. Three different genetic RYR1 variants (c.5360C>T, c.6178G>T, and c.7244G>A) were identified in the study. The G/T genotype of RYR1 c.6178G>T was associated with an increased risk for development of symptomatic vasospasm (odds ratio 6.4; 95% CI 1.1-37.8; P = 0.04). Our pilot study suggests that RYRs are involved in the complex pathophysiology of vasospasm development following SAH. The potential role of RYR1 as a biomarker for prediction of cerebral vasospasm after SAH has to be confirmed in a larger clinical trial.
  Neurocritical Care 04/2011; 15(3):410-5. · 2.47 Impact Factor
• Article: Integration of a 3D ultrasound probe into neuronavigation.

  Andrea Müns, Jürgen Meixensberger, Sven Arnold, Arno Schmitgen, Felix Arlt, Claire Chalopin, Dirk Lindner
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  ABSTRACT: Intraoperative ultrasound (iUS) allows the generation of real-time data sets during surgical interventions. The recent innovation of 3D ultrasound probes permits the acquisition of 3D data sets without the need to reconstruct the volume by 2D slices. This article describes the integration of a tracked 3D ultrasound probe into a neuronavigation. An ultrasound device, provided with both a 2D sector probe and a 3D endocavity transducer, was integrated in a navigation system with an optical tracking device. Navigation was performed by fusion of preoperatively acquired MRI data and intraoperatively acquired ultrasound data throughout an open biopsy. Data sets with both probes were acquired transdurally and compared. The acquisition with the 3D probe, processing and visualization of the volume only took about 2 min in total. The volume data set acquired by the 3D probe appears more homogeneous and offers better image quality in comparison with the image data acquired by the 2D probe. The integration of a 3D probe into neuronavigation is possible and has certain advantages compared with a 2D probe. The risk of injury can be reduced, and the application can be recommended for certain cases, particularly for small craniotomies.
  Acta Neurochirurgica 04/2011; 153(7):1529-33. · 1.52 Impact Factor
• Article: Traumatic brain injury elicits similar alterations in α7 nicotinic receptor density in two different experimental models.

  Peter-Georg Hoffmeister, Cornelius K Donat, Martin U Schuhmann, Cornelia Voigt, Bernd Walter, Karen Nieber, Jürgen Meixensberger, Reinhard Bauer, Peter Brust
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  ABSTRACT: Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. Previous studies have shown alterations in the central cholinergic neurotransmission after TBI. We therefore determined α7 nicotinic acetylcholine receptor (nAChR) densities in newborn piglets and adult rats after experimental TBI. Thirteen newborn piglets (post-TBI survival time: 6 h) underwent fluid percussion (FP) injury (n = 7) or sham operation (n = 6). Furthermore, adult rats randomized into three groups of post-TBI survival times (2, 24, 72 h) received controlled cortical impact injury (CCI, n = 8) or sham operation (n = 8). Brains were frozen, sagittally cut and incubated with the α7-specific radioligand [(125)I]α-bungarotoxin for autoradiography. In injured newborn piglets, decreased α7 receptor densities were observed in the hippocampus (-38%), the hippocampus CA1 (-40%), thalamus (-30%) and colliculus superior (-30%). In adult rats, CCI decreased the receptor densities (between -16 and -47%) in almost any brain region within 2 and 24 h. In conclusion, widespread and significantly lowered α7 nAChR densities were demonstrated in both TBI models. Our results suggest that a nearly similar TBI-induced decrease in the α7 density in the brain of immature and adult animals is found, even with the differences in species, age and experimental procedures. The alterations make the α7 nAChR a suitable target for drug development and neuroimaging after TBI.
  Neuromolecular medicine 03/2011; 13(1):44-53. · 5.00 Impact Factor
• Article: Intracranial hemangiopericytoma: Case study with cytogenetics and genome wide SNP-A analysis.

  Heidrun Holland, Michela Livrea, Peter Ahnert, Ronald Koschny, Holger Kirsten, Jürgen Meixensberger, Manfred Bauer, Ralf Schober, Dominik Fritzsch, Wolfgang Krupp
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  ABSTRACT: The tumor entity of hemangiopericytoma is not universally recognized as a nosological entity by pathologists, and there is a trend toward reassigning it to other categories gradually. However, hemangiopericytomas occurring in the nervous system are included in the new WHO classification of brain tumors, and are distinguished from both meningioma and fibrous tumors. Since there are few genetic studies, we performed a comprehensive cytogenetic analysis of an infratentorial hemangiopericytoma in a 55-year-old female. It was originally classified as a grade II tumor but recurred as a grade III tumor with a proliferation index of 20%. Using trypsin-Giemsa staining (GTG-banding) and multicolor fluorescence in situ hybridization (M-FISH), we could confirm the loss of chromosomal material 10q, which has been previously described in hemangiopericytoma, and we identified de novo chromosomal aberrations on chromosome 8. Applying genome-wide high-density single nucleotide polymorphism array (SNP-A) analysis, we detected segments with loss or gain, as well as clonal deletions or regions suggestive of segmental uniparental disomy. These findings, together with the results of conventional histological and immunohistochemical characterization, provide additional evidence for the nosological separation of hemangiopericytoma in the central nervous system as a biologically different entity.
  Pathology - Research and Practice 02/2011; 207(5):310-6. · 1.21 Impact Factor
• Article: Comment to the article: Foramen magnum meningioma: successful surgical resection in a 76-year-old Nigerian.

  Jürgen Meixensberger
  Central European neurosurgery 02/2011; 72(1):46. · 0.84 Impact Factor
• Article: Identification of factors involved in the anti-tumor activity of carnosine on glioblastomas using a proteomics approach.

  Ansgar Asperger, Christof Renner, Mandy Menzel, Rolf Gebhardt, Jürgen Meixensberger, Frank Gaunitz
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  ABSTRACT: Human glioblastoma multiforme is the most malignant brain tumor in adults and is difficult to treat. Recently, it was demonstrated that the dipeptide carnosine inhibits tumor growth, but the main molecular targets are not known. Therefore, a proteomics study with glioblastoma cells treated with carnosine was performed. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight detected 31 proteins expressed differentially under the influence of carnosine. Finally, peptide mass fingerprinting identified the "BCL2-associated athanogene 2" and the "von Hippel-Lindau binding protein 1" among other proteins, linking the action of carnosine to protein folding and HIF-1α signalling.
  Cancer Investigation 02/2011; 29(4):272-81. · 1.85 Impact Factor