Propentdyopents as Heme Degradation Intermediates Constrict Mouse Cerebral Arterioles and Are Present in the Cerebrospinal Fluid of Patients With Subarachnoid Hemorrhage.

RATIONALE: Delayed ischemic neurological deficit is the most common cause of neurological impairment and unfavorable prognosis in patients with subarachnoid hemorrhage (SAH). Despite the existence of neuroimaging modalities that depict the onset of the accompanying cerebral vasospasm, preventive and therapeutic options are limited and fail to improve outcome owing to an insufficient pathomechanistic understanding of the delayed perfusion deficit. Previous studies have suggested that BOXes (bilirubin oxidation end products), originating from released heme surrounding ruptured blood vessels, are involved in arterial vasoconstriction. Recently, isolated intermediates of oxidative bilirubin degradation, known as PDPs (propentdyopents), have been considered as potential additional effectors in the development of arterial vasoconstriction. OBJECTIVE: To investigate whether PDPs and BOXes are present in hemorrhagic cerebrospinal fluid and involved in the vasoconstriction of cerebral arterioles. METHODS AND RESULTS: Via liquid chromatography/mass spectrometry, we measured increased PDP and BOX concentrations in cerebrospinal fluid of SAH patients compared with control subjects. Using differential interference contrast microscopy, we analyzed the vasoactivity of PDP isomers in vitro by monitoring the arteriolar diameter in mouse acute brain slices. We found an arteriolar constriction on application of PDPs in the concentration range that occurs in the cerebrospinal fluid of patients with SAH. By imaging arteriolar diameter changes using 2-photon microscopy in vivo, we demonstrated a short-onset vasoconstriction after intrathecal injection of either PDPs or BOXes. Using magnetic resonance imaging, we observed a long-term PDP-induced delay in cerebral perfusion. For all conditions, the arteriolar narrowing was dependent on functional big conductance potassium channels and was absent in big conductance potassium channels knockout mice. CONCLUSIONS: For the first time, we have quantified significantly higher concentrations of PDP and BOX isomers in the cerebrospinal fluid of patients with SAH compared to controls. The vasoconstrictive effect caused by PDPs in vitro and in vivo suggests a hitherto unrecognized pathway contributing to the pathogenesis of delayed ischemic deficit in patients with SAH.

A biomechanical comparison of a cement-augmented odontoid screw with a posterior-instrumented fusion in geriatric patients with an odontoid fracture type IIb.

PURPOSE: Possible surgical therapies for odontoid fracture type IIb include odontoid screw osteosynthesis (OG) with preservation of mobility or dorsal C1/2 fusion with restriction of cervical rotation. In order to reduce material loosening in odontoid screw osteosynthesis in patients with low bone density, augmentation at the base of the axis using bone cement has been established as a suitable alternative. In this study, we compared cement-augmented OG and C1/2 fusion according to Harms (HG). METHODS: Body donor preparations of the 1st and 2nd cervical vertebrae were randomized in 2 groups (OG vs. HG). The range of motion (ROM) was determined in 3 principle motion plains. Subsequently, a cyclic loading test was performed. The decrease in height of the specimen and the double amplitude height were determined as absolute values as an indication of screw loosening. Afterward, the ROM was determined again and loosening of the screws was measured in a computed tomography. RESULTS: A total of 16 were included. Two groups of 8 specimens (OG vs. HG) from patients with a median age of 80 (interquartile range (IQ) 73.5-85) years and a reduced bone density of 87.2 (IQ 71.2-104.5) mg/cc dipotassium hydrogen phosphate were examined for their biomechanical properties. Before and after exposure, the OG preparations were significantly more mobile. At the time of loading, the OG had similar loading properties to HG decrease in height of the specimen and the double amplitude height. Computed tomography revealed similar outcomes with regard to the screw loosening rate (62.5 vs. 87.5%, p = 0.586). CONCLUSION: In patients with an odontoid fracture type IIb and reduced bone density, cement-augmented odontoid screw yielded similar properties in the loading tests compared to the HG. It may, therefore, be considered as a primary alternative to preserve cervical mobility in these patients.

[What became of Prialt®? : Observational study on the use of ziconotide in the treatment of chronic pain]. / Was wurde eigentlich aus Prialt®? : Beobachtungsstudie über den Langzeiteinsatz von Ziconotid in der Behandlung chronischer Schmerzen.

BACKGROUND: Prialt® was approved by the European Medicine Agency in February 2005. Besides morphine, it is the only analgesic approved for long-term intrathecal infusion in the treatment of chronic pain. As it does not bind to opioid receptors, its use in the treatment of chronic pain seemed to be safer and to lead to less adverse events compared with morphine. However, it is an orphan drug and studies of its long-term use are rare. QUESTIONS: What role does Prialt® play in the treatment of chronic pain compared with other analgesics given intrathecally? What impact do the initial dose and the rate of infusion have on the analgesic effect and on the incidence of side effects? MATERIAL AND METHODS: Medical reports were used to identify all patients receiving ziconotide monotherapy from February 2005 to the end of the analysis period in October 2018 in our department. Furthermore, a questionnaire was created and given to the patients to find out more about their experience with ziconotide. RESULTS: The study included 12 patients, all of whom suffered from at least one adverse event. The most common adverse events were forgetfulness and paraesthesia, each affecting 25% of the patients. One third of the patients discontinued ziconotide therapy due to severe adverse events. The mean initial dose was 1.98 µg/day. DISCUSSION: Ziconotide was used at the Jena University Hospital according to the latest guidelines. Nevertheless, morphine and other opioid analgesics are still more frequently used in the intrathecal management of chronic pain. There are various reasons for this, but the narrow therapeutic index, the high incidence of adverse events, and the difficulties in finding the right dose are among the most important.

Prospective randomized comparison of early versus newer-generation vertebral access devices for kyphoplasty.

INTRODUCTION: Kyphoplasty is an established method of treating osteoporotic vertebral body compression fractures. In recent years, several techniques to enhance the efficiency and outcomes of this surgery have been developed and implemented in clinical practice. In the present study, we assess the impact of two new access instruments on overall operation time and the administered dose area product in comparison with the standard access instrument used in our clinical practice. The two newer comparator devices have been designed with the intention of streamlining intraoperative workflow by omitting several procedural steps. MATERIALS AND METHODS: This was a single-center prospective randomized trial investigating three distinct access instruments compatible with the Joline Allevo balloon catheter system. Specifically, two newer access devices marketed as being able to enhance surgical workflow (Joline RapidIntro Vertebra Access Device with a trocar tip and Joline SpeedTrack Vertebra Introducer Device with a short, tapered tip) were compared with the older, established Joline Vertebra Access Device from the same firm. Consecutive eligible and consenting patients scheduled to undergo kyphoplasty for osteoporotic vertebral compression fracture refractory to conservative, medical treatment during the period May 2012-August 2015 were randomized to receive surgery using one of the three devices. Besides the use of the trial instruments, all other preoperative, intraoperative and postoperative care was delivered according to standard practice. RESULTS: 91 kyphoplasties were performed on 65 unique patients during the study period. The median operation time across the three groups was 29 min (IQR 22.5-35.5) with a median irradiation time of 2.3 min (IQR 1.2-3.4). The median patient age was 74 years (IQR 66-80). The groups did not significantly differ in terms of age (p = 0.878), sex (p = 0.37), T score (p = 0.718), BMI (p = 0.285) or the applied volume of cement (p = 0.792). There was no significant difference between the treatment groups with respect to surgical duration (p = 0.157) or dose area product (p = 0.913). CONCLUSIONS: Although use of the two newer-generation access instruments were designed to involve fewer unique steps per operation, their use was not associated with reduction in surgical duration, irradiation time or dose area product administered compared with the older, established vertebral access device. Care should be taken to evaluate the impact of new instruments on key surgery-related parameters such as surgical duration and radiation exposure and claims made about new instruments should be assessed a structured fashion.

Spinal Cord Stimulation for Acute Pain Following Surgery for Cervical Myelopathy: A Novel Treatment Strategy.

BACKGROUND: Chronic pain syndromes caused by degenerative and postinfectious changes in the cervical spine continue to pose significant management challenges to neurosurgeons and pain practitioners. The identification of an individualized treatment plan, astute surgical technique, comprehensive and multimodal analgesia, and adequate rehabilitation processes do not necessarily result in diminished pain. CASE SUMMARY: We present the case of a patient with chronic pain treated surgically for degenerative cervical myelopathy secondary to cervical spinal stenosis. Following this surgery, the patient experienced an intractable postoperative pain syndrome that had anatomical borders, and an intensity and character that were different from the background chronic pain from which he suffered. We successfully implanted a cervical spinal cord stimulation (SCS) lead in the period following his stenosis surgery, which had good therapeutic effect on the postoperative-onset pain. To the best of our knowledge, this is the first description of SCS having a strong positive effect on an acute exacerbation of neuropathic pain. At follow-up 12 months later, assessment of the patient's pain diary revealed a modal pain intensity of 3/10 on the numeric rating scale over the preceding 3 months. The Brief Pain Inventory (Short Form) scores at this time were 10/40 in the pain severity domain and 18/70 in the interference with function domain, demonstrating the long-term effectiveness of this SCS strategy. CONCLUSION: While SCS has hitherto been untested as a therapy for acute-onset pain, this report demonstrates its utility as a salvage treatment in select cases of uncontrollable postoperative pain.

Achievable Central Nervous System Concentrations of the Green Tea Catechin EGCG Induce Stress in Glioblastoma Cells in Vitro.

The polyphenolic compounds present in green tea are preventative against cancer in several animal tumor models. However, direct cytotoxic effects on cancer cells have also been reported. In order to determine whether drinking of green tea has chemopreventive or cytotoxic effects on brain cancer cells, we investigated the effect of the major green tea polyphenol EGCG as a pure substance and as tea extract dietary supplement on primary human glioblastoma cell cultures at the CNS-achievable concentration of 100 nM reported in the literature. We compared this with the effect of the cytotoxic concentration of 500 µM determined to be specific for the investigated primary glioblastoma cultures. After treatment with 500 µM EGCG, strong induction of autophagy and apoptosis was observed. Under treatment with 100 nM EGCG, glioblastoma cells proliferated over the entire observation period of 6 days without any detectable signs of cell death. Only within the first 12 h of treatment was increased accumulation of autophagic vacuoles and increased reactive oxygen species production as a stress response demonstrated. Mild forms of stress, such as treatment with 100 nM EGCG, activate different endogenous repair mechanisms to protect cells. Our data imply that drinking of green tea may have chemopreventive effects, but no direct cytotoxic properties.

Cost-effectiveness of the long-term use of temozolomide for treating newly diagnosed glioblastoma in Germany.

Concomitant radiochemotherapy followed by six cycles of temozolomide (= short term) is considered as standard therapy for adults with newly diagnosed glioblastoma. In contrast, open-end administration of temozolomide until progression (= long-term) is proposed by some authors as a viable alternative. We aimed to determine the cost-effectiveness of long-term temozolomide therapy for patients newly diagnosed with glioblastoma compared to standard therapy. A Markov model was constructed to compare medical costs and clinical outcomes for both therapy types over a time horizon of 60 months. Transition probabilities for standard therapy were calculated from randomized controlled trial data by Stupp et al. The data for long-term temozolomide therapy was collected by matching a cohort treated in the Department of Neurosurgery at Jena University Hospital. Health utilities were obtained from a previous cost utility study. The cost perspective was based on health insurance. The base case analysis showed a median overall survival of 17.1 months and a median progression-free survival of 7.4 months for patients in the long-term temozolomide therapy arm. The cost-effectiveness analysis using all base case parameters in a time-dependent Markov model resulted in an incremental effectiveness of 0.022 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was €351,909/QALY. Sensitivity analyses showed that parameters with the most influence on ICER were the health state utility of progression in both therapy arms. Although open-ended temozolomide therapy is very expensive, the ICER of this therapy is comparable to that of the standard temozolomide therapy for patients newly diagnosed with glioblastoma.

NANOG overexpression and its correlation with stem cell and differentiation markers in meningiomas of different WHO grades.

NANOG, as a key regulator of pluripotency and acting synergistically with other factors, has been described as a crucial transcription factor in various types of cancer. In meningiomas the expression of this marker has not yet been described. With our study, we aimed to identify and localize NANOG and other possible markers of pluripotency, stem cell properties and differentiation in meningioma tissue, to elucidate a possible effect on tumorigenesis. The gene expression levels of NANOG (NANOG1 and NANOGP8), SOX2, OCT4, KLF4, ABCG2, CMYC, MSI1, CD44, NOTCH1, NES, SALL4B, TP53, and EPAS1 were quantitatively examined using RT-qPCR in 33 surgical specimens of low- (WHO grade I) as well as in high-grade (WHO grade II/III) meningiomas with dural tissue as reference. Immunofluorescence co-localization analysis following confocal fluorescence microscopy for NANOG, OCT4, SOX2, Nestin, KI-67, and CD44 was also performed. There was a significant overexpression of NANOG, MSI1, and EPAS1 and a downregulation of NES in all examined tumors. Subgroup analysis (WHO grade I versus grade II/III) revealed differences in the expression of NANOG, CD44, and MSI1. We found 1% NANOG-positive (NANOG+) cells in low-grade and 2% in grade II/III meningiomas co-expressing the other mentioned markers in various compositions. In particular, NANOG+ cells expressing SOX2 and OCT4 were successfully identified (26% low-grade versus 20% high-grade). Our data reveal an overexpression of NANOG and other markers of pluripotency and stemness in meningiomas. Such potentially pluripotent "stem cell-like" cells may have an impact on tumorigenesis and progression in human meningiomas.

Cement-augmented anterior odontoid screw fixation for osteoporotic type II odontoid fractures in elderly patients: prospective evaluation of 11 patients.

PURPOSE: Osteoporosis is considered to be a relative contraindication for anterior screw fixation of odontoid fractures because of reduced screw purchase. In the presence of osteoporosis, the most frequent mode of implant failure is via cut-out through the anterior wall of C2. Under in vitro conditions, cement-augmented odontoid screws show significant biomechanical advantages as compared to non-augmented screws. Against this background, we present our prospectively collected data on cement-augmented anterior screw fixation of osteoporotic odontoid fractures in elderly patients. METHODS: 11 patients (8 female, 3 male, median age 83 years, range 73-89 years) with an isolated, osteoporotic type II odontoid fracture were treated. After closed reduction and standard anterior approach to the C2/3 level, a self-tapping, short-threaded 3.5-mm lag screw was placed. High-viscosity polymethylmethacrylate cement was injected via a cannulated Jamshidi needle into the base of the C2 vertebral body around the screw shaft and the screw was further tightened. Thin slice CT reconstructions for follow-up evaluation were done consistently postop and 12 months after surgery. RESULTS: Anatomic fracture reposition was achieved in all patients. Cement application was uneventful and well controllable. Cement leakage towards the fracture gap was not detectable. There were no major perioperative complications and no early revision surgeries. After 1 year, thin slice CT with three-dimensional reconstruction demonstrated solid osseous healing of the odontoid fracture in 8 out of 10 patients. CONCLUSIONS: Additional cement augmentation for anterior odontoid fracture repair is technically easy and safe. In elderly people with osteoporotic odontoid fractures, the procedure seems to be a useful supplementary option.

Selection of suitable reference genes for expression analysis in human glioma using RT-qPCR.

In human glioma research, quantitative real-time reverse-transcription PCR is a frequently used tool. Considering the broad variation in the expression of candidate reference genes among tumor stages and normal brain, studies using quantitative RT-PCR require strict definition of adequate endogenous controls. This study aimed at testing a panel of nine reference genes [beta-2-microglobulin, cytochrome c-1 (CYC1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hydroxymethylbilane synthase, hypoxanthine guanine phosphoribosyl transferase 1, ribosomal protein L13a (RPL13A), succinate dehydrogenase, TATA-box binding protein and 14-3-3 protein zeta] to identify and validate the most suitable reference genes for expression studies in human glioma of different grades (World Health Organization grades II-IV). After analysis of the stability values calculated using geNorm, NormFinder, and BestKeeper algorithms, GAPDH, RPL13A, and CYC1 can be indicated as reference genes applicable for accurate normalization of gene expression in glioma compared with normal brain and anaplastic astrocytoma or glioblastoma alone within this experimental setting. Generally, there are no differences in expression levels and variability of candidate genes in glioma tissue compared to normal brain. But stability analyses revealed just a small number of genes suitable for normalization in each of the tumor subgroups and across these groups. Nevertheless, our data show the importance of validation of adequate reference genes prior to every study.

Cement augmented anterior odontoid screw fixation is biomechanically advantageous in osteoporotic patients with Anderson Type II fractures.

STUDY DESIGN: A biomechanical human cadaveric study. OBJECTIVE: The authors tested a cannulated and perforated lag screw and compared in situ polymethylmethacrylate (PMMA) augmentation against nonaugmentation for fixation of osteoporotic type II odontoid fractures. SUMMARY OF BACKGROUND DATA: Osteoporosis has been identified as a strong predictor for pseudarthrosis after screw fixation of type II odontoid fractures with cut-out through the anterior wall of C2 as the most frequent mode of implant failure. The concept of PMMA augmentation of the proximal screw shank could serve as a useful supplement in this context. METHODS: A total of 18 fresh-frozen human cadaveric C2 vertebrae were harvested (median 86.5 y; range, 69-98 y). Reduced bone quality was verified by quantitative computed tomography. Type II odontoid fractures were created and repaired with a cannulated lag screw, which has perforations in the proximal screw shank. Additional PMMA augmentation was carried out for 9 specimens. The position of the screw and cement distribution were evaluated by computed tomography. Values for maximum force to failure, energy to failure, and stiffness were statistically compared between cement augmented and nonaugmented screws. RESULTS: Cement distribution in the C2 vertebral body was circumferential around the screw shank without leakage into the spinal canal or into the fracture gap in all 9 specimens. The cement augmented screws showed a 2.4 times higher maximum force to failure (363±94 N, P<0.001), a 2.7 times higher energy to failure (1300±698 mJ, P<0.001), and a 1.76 times higher stiffness (90±35 N/mm, P=0.031) in comparison with the nonaugmented screws. CONCLUSIONS: Cement augmentation for fixation of osteoporotic type II odontoid fractures showed biomechanical advantages. It was also shown that cement augmentation of the newly developed screw is technically easy and safe under in vitro conditions. The technique might be useful with regard to the surgical treatment of elderly patients with osteoporotic odontoid fractures.

Methylation-specific multiplex ligation-dependent probe amplification and its impact on clinical findings in medulloblastoma.

Gain of (proto-)oncogenes and loss or promoter hypermethylation of tumor suppressor genes (TSGs) play essential roles in tumorigenesis. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) allows simultaneous detection of both these alterations. MS-MLPA was performed on 20 medulloblastoma samples (n = 12 cryoconserved; n = 8 formalin-fixed paraffin-embedded, FFPE) in order to screen for copy number changes in 77 unselected TSGs and (proto-)oncogenes as well as for promoter hypermethylation in a subset of 33 TSGs. In all specimens, determination of promoter methylation status was possible, whereas robust data concerning copy number changes could be obtained on cryopreserved material only. We found a median of 1.5 deletions and 6.5 amplifications in the 12 cryopreserved medulloblastoma and a median of 5 promoter hypermethylation per tumor. Frequent copy number changes included amplification of ASC on 16p12 (5/12) and amplification of several adjacent genes on 17q (3/12) including IGFBP4. Hypermethylation of MSH6 on 2p16 was found in 16 samples. MS-MLPA findings were also correlated with clinical and histological characteristics. The number of promoter hypermethylation was significantly associated with presence of necrosis (p = 0.004). Tumors which recurred within 1 year were more likely to show amplification of the GATA5 gene (p = 0.038), while hypermethylation of CASP8 was associated with a lower tumor recurrence rate (p = 0.036). There was also a trend towards a correlation between total number of aberrations and CSF dissemination (p = 0.055). Our findings confirm frequent presence of certain aberrations and reveal novel candidates for improving prognosis based on genetic and epigenetic tumor features. A medulloblastoma-specific MS-MLPA probe set seems a potentially valuable tool for further investigations on larger sample series.

Overexpression of fatty acid synthase in human gliomas correlates with the WHO tumor grade and inhibition with Orlistat reduces cell viability and triggers apoptosis.

Fatty acid synthase (FASN), catalyzing the de novo synthesis of fatty acids, is known to be deregulated in several cancers. Inhibition of this enzyme reduces tumor cell proliferation. Unfortunately, adverse effects and chemical instability prevent the in vivo use of the best-known inhibitors, Cerulenin and C75. Orlistat, a drug used for obesity treatment, is also considered as a potential FASN inhibitor, but its impact on glioma cell biology has not yet been described. In this study, we analyzed FASN expression in human glioma samples and primary glioblastoma cell cultures and the effects of FASN inhibition with Orlistat, Cerulenin and C75. Immunohistochemistry followed by densitometric analysis of 20 glioma samples revealed overexpression of FASN that correlated with the WHO tumor grade. Treatment of glioblastoma cells with these inhibitors resulted in a significant, dose-dependent reduction in tumor cell viability and fatty acid synthesis. Compared to Cerulenin and C75, Orlistat was a more potent inhibitor in cell cultures and cell lines. In LN229, cell-growth was reduced by 63.9 ± 8.7 % after 48 h and 200 µM Orlistat compared to controls; in LT68, the reduction in cell growth was 76.3 ± 23.7 %. Nuclear fragmentation assay and Western blotting analysis after targeting FASN with Orlistat demonstrated autophagy and apoptosis. Organotypic slice cultures treated with Orlistat showed reduced proliferation after Ki67 staining and increased caspase-3 cleavage. Our results suggest that FASN may be a therapeutic target in malignant gliomas and identify Orlistat as a possible anti-tumor drug in this setting.

Denervation and atrophy of paraspinal muscles after open lumbar interbody fusion is associated with clinical outcome--electromyographic and CT-volumetric investigation of 30 patients.

BACKGROUND: Different studies have shown that atrophy of paraspinal muscles arises after open dorsal lumbar fusion, and the reasons for this atrophy are still not yet fully clarified. This prospective study investigates the extent of atrophy of the lumbar paraspinal muscles after open lumbar interbody fusion, its possible causes, and their association with clinical outcome measures. METHODS: Thirty consecutive patients were prospectively included (13 male, 17 female, median age 60.5 years, range 33-80 years). Mono or bisegmental, posterior lumbar interbody fusion and instrumentation was performed applying a conventional, open lumbar midline approach. Clinical outcome was assessed by the Short Form (36) Health Survey (SF-36) questionnaire and visual analogue scale. Needle electromyography of paraspinal muscles was performed preoperatively, at 6 and 12 months. Serum values of creatine kinase, lactate dehydrogenase and myoglobin were determined preoperatively, at day 2 after surgery and at discharge. Paraspinal muscle volume was determined by volumetric analysis of thin-slice computed tomography scans preoperatively and 1 year after surgery. RESULTS: There was a significant increase of electromyographic denervation activity (p =0.024) and reduced recruitment of motor units (p = 0.001) after 1 year. Laboratory studies showed a significant increase of CK (p < 0.001) and myoglobin (p < 0.001) serum levels at day 2 after surgery. The paraspinal muscle volume decreased from 67.8 to 60.4 % (p < 0.001) after 1 year. Correlation analyses revealed a significant negative correlation between denervation and muscle volume (K = -0.219, p = 0.002). Paraspinal muscle volume is significantly correlated with physical outcome (K = 0.169, p = 0.020), mental outcome (K = 0.214, p = 0.003), and pain (K = 0.382, p < 0.001) after 1 year. CONCLUSIONS: Atrophy of paraspinal muscles after open, posterior lumbar interbody fusion seems to be associated with denervation, as well as direct muscle trauma during surgery. While muscle atrophy is also correlated with a worse clinical outcome, it seems to be a determining factor for successful lumbar spine surgery.

Bone flap necrosis after decompressive hemicraniectomy for malignant middle cerebral artery infarction.

BACKGROUND: Autologous bone flap reinsertion follows as a second surgical intervention after decompressive craniectomy in patients with malignant middle cerebral artery (MCA) infarction. In addition to surgery-related short-term complications, aseptic resorption of the reimplanted bone flap is a possible long-term problem which has not yet been sufficiently elucidated in these patients. METHODS: A total of 109 patients who had undergone decompressive hemicraniectomy for malignant MCA infarction in our institution between September 1994 and December 2011 were included in the study. Clinical and radiological findings were retrieved retrospectively. Aseptic bone necrosis was classified into two categories based on computer tomographic features. RESULTS: A total of 76 patients received their own cryoconserved bone flap (mean age 54.34 ± 10.73 years; 49 males). The overall short-term complication rate was 9.2 %. Bone flap necrosis occurred in 26 patients (22.8 %) with 7 flaps showing signs of surgically relevant type II necrosis after a median time of 14 months (interquartile range [IQR] 4-22). CONCLUSIONS: There is a noticeable complication rate in patients undergoing bone flap reinsertion after hemicraniectomy due to malignant MCA infarction. Aseptic bone necrosis represents a significant complication during long-term follow-up. The pathophysiological mechanisms remain unclear and more efforts should be undertaken to understand and possibly prevent this complication in these patients.

Tumor margin identification and prediction of the primary tumor from brain metastases using FTIR imaging and support vector machines.

Infrared spectroscopy enables the identification of tissue types based on their inherent vibrational fingerprint without staining in a nondestructive way. Here, Fourier transform infrared microscopic images were collected from 22 brain metastasis tissue sections of bladder carcinoma, lung carcinoma, mamma carcinoma, colon carcinoma, prostate carcinoma and renal cell carcinoma. The scope of this study was to distinguish the infrared spectra of carcinoma from normal tissue and necrosis and to use the infrared spectra of carcinoma to determine the primary tumor of brain metastasis. Data processing follows procedures that have previously been developed for the analysis of Raman images of these samples and includes the unmixing algorithm N-FINDR, segmentation by k-means clustering, and classification by support vector machines (SVMs). Upon comparison with the subsequent hematoxylin and eosin stained tissue sections of training specimens, correct classification rates of the first level SVM were 98.8% for brain tissue, 98.4% for necrosis and 94.4% for carcinoma. The primary tumors were correctly predicted with an overall rate of 98.7% for FTIR images of the training dataset by a second level SVM. Finally, the two level discrimination models were applied to four independent specimens for validation. Although the classification rates are slightly reduced compared to the training specimens, the majority of the infrared spectra of the independent specimens were assigned to the correct primary tumor. The results demonstrate the capability of FTIR imaging to complement histopathological tools for brain tissue diagnosis.

CT-navigation versus fluoroscopy-guided placement of pedicle screws at the thoracolumbar spine: single center experience of 4,500 screws.

PURPOSE: Single center evaluation of the placement accuracy of thoracolumbar pedicle screws implanted either with fluoroscopy or under CT-navigation using 3D-reconstruction and intraoperative computed tomography control of the screw position. There is in fact a huge variation in the reported placement accuracy of pedicle screws, especially concerning the screw placement under conventional fluoroscopy most notably due to the lack of the definition of screw misplacement, combined with a potpourri of postinstrumentation evaluation methods. METHODS: The operation data of 1,006 patients operated on in our clinic between 1995 and 2005 is analyzed retrospectively. There were 2,422 screws placed with the help of CT-navigation compared to 2,002 screws placed under fluoroscopy. The postoperative computed tomography images were reviewed by a radiologist and an independent spine surgeon. RESULTS: In the lumbar spine, the placement accuracy was 96.4 % for CT-navigated screws and 93.9 % for pedicle screws placed under fluoroscopy, respectively. This difference in accuracy was statistically significant (Fishers Exact Test, p = 0.001). The difference in accuracy became more impressing in the thoracic spine, with a placement accuracy of 95.5 % in the CT-navigation group, compared to 79.0 % accuracy in the fluoroscopy group (p < 0.001). CONCLUSION: This study underlines the relevance of CT-navigation-guided pedicle screw placement, especially when instrumentation of the middle and upper thoracic spine is carried out.

Expandable titanium cages for anterior column cervical reconstruction and their effect on sagittal profile: a review of 48 cases.

BACKGROUND: Expandable cervical cages have been utilised successfully to reconstruct the cervical spine for various conditions. However, to date there are only limited data on their influence on cervical sagittal profile. In this retrospective study, we present our experience with performing anterior cervical corpectomy in one or two levels using expandable titanium cages in order to achieve stable reconstruction and restoration of cervical lordosis. METHODS: A case series of data from 48 consecutive patients (20 men, 28 women; mean age 61 years) operated upon in a 5-year-period is retrospectively reviewed. Standard anterior single- or two-level cervical corpectomy, fusion and spinal reconstruction were performed, including placement of an expandable titanium cage and an anterior cervical plate. The mean follow-up was 23 months (range, 8-42 months). Outcome was measured by clinical examinations and visual analogue scale (VAS) scale; myelopathy was classified according the Nurick grading system. Radiographic analysis comprised several parameters, including segmental Cobb angle, cervical lordosis, subsidence ratio and sagittal cage angle. Computed tomography was done 1 and 2 years after surgery; cervical spine radiographs were obtained 3, 6, 12 and 24 months after surgery. RESULTS: In 38 patients (79 %) osseous fusion or stability of construct could be demonstrated in the 2-year follow up examination. The mean restoration of segmental Cobb angle as well as cervical lordosis amounted to 7.6° and 5.4° respectively, both being statistically significant. Furthermore, a profound correction (10° or more) of the sagittal cervical curve was shown in 15 patients. CONCLUSION: Regarding the restoration of the physiological sagittal cervical profile, expandable cervical cages seem to be efficient and easy to use for cervical spine reconstruction after anterior corpectomy. Donor-site-related complications are avoided, fast and strong reconstruction of the anterior column is provided, resulting in satisfactory fusion rates after 2 years.

Anterior cervical intercorporal fusion in patients with osteoporotic or tumorous fractures using a cement augmented cervical plate system: first results of a prospective single-center study.

STUDY DESIGN: Prospective observational clinical study. OBJECTIVE: The aim of this study is to evaluate the technical feasibility and the safety of additional cement augmentation of anterior cervical implants in patients with poor bone quality because of osteoporosis or tumor infiltration. SUMMARY OF BACKGROUND DATA: With an increasing number of elderly patients in spinal surgery the problem of implant dislocation after cervical instrumentation will become a more and more important problem. Whereas in the thoracolumbar area cement augmented screws have become widely accepted to ensure a rigid fixation in patients with reduced bone quality there are no data concerning an additional intravertebral cement augmentation after cervical plating. METHODS: Nine patients (4 males, 5 females, mean age 62.8 y) with newly diagnosed fractures of 1 or 2 cervical vertebrae because of tumor infiltration (6 cases) or osteoporosis (3 cases) were included in our study. A standard 1-level or 2-level cervical corpectomy with vertebral body replacement by an in situ expandable titanium cage and additional anterior plating was carried out. After this, additional cement augmentation was performed as a vertebroplasty of the anterior two thirds of the cranial and caudal adjacent vertebra by a new anterior hole. The cement should enclose the screws and stabilize the endplates of the adjacent vertebrae. Follow-up comprised clinical examinations, SF-36 questionnaire and visual analog scale 3, 6, and 12 months after surgery. Cervical spine radiographs were obtained 3 and 6 months after surgery and computed tomography scans 6 and 12 months after surgery. RESULTS: The median follow-up was 10 months with a range of 4-18 months. There was no intraoperative cement leakage into the spinal canal. The visual analog scale decreased from 8.2 to 4.2 at 6 months, physical and mental component summaries of SF-36 increased significantly from 27.7 to 36.1 and 31.5 to 48.6 at 6 months, respectively. Loosening of screws or plates was not detected throughout the whole observation period. There was 1 subsidence of a titanium cage into an adjacent vertebra without any clinical consequences. There was no adjacent fracture during the follow-up period and other surgical interventions or revisions were not necessary in any patient. CONCLUSIONS: In patients with severe osteoporosis or in patients with advanced tumor disease, excellent surgical, clinical, and radiologic results are possible following our method. In our opinion, a second-step posterior approach can be avoided by this technique.