[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.

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.

Time course of the response to navigated repetitive transcranial magnetic stimulation at 10 Hz in chronic neuropathic pain.

Objective This prospective study evaluated the time to response and outcomes of navigated repetitive transcranial magnetic stimulation (TMS) at a frequency of 10 Hz in patients with chronic neuropathic pain. Methods This prospective study included patients with unilateral chronic neuropathic pain. All patients received motor cortex stimulation at 10 Hz over nine consecutive days using repetitive TMS. Outcome was evaluated over a six-week follow-up period using the visual analogue scale, the German Pain Questionnaire and time to pain reduction. Results Fifty patients (23 female, 27 male) were recruited. Two patients were excluded from analysis owing to premature discontinuation of treatment and follow-up. 31/48 patients in the cohort suffered from atypical facial pain. The pain duration ranged approximately from six months to 27 years. After six weeks, 28/46 patients reported a significant level of pain relief (P < 0.001). Conclusion Navigated repetitive TMS for chronic pain is a non-invasive modality with demonstrable clinical benefit. In particular, patients with atypical facial pain with a clear clinicoanatomical correlate responded well to high-frequency stimulation. Patients with a mean pain history of less than five years benefited significantly from this treatment, so early treatment with repetitive TMS should be encouraged.

Biplanar Fluoroscopy-Guided Percutaneous Lead Implantation for Spinal Cord Stimulation: Technical Note.

INTRODUCTION: The correct positioning of spinal cord stimulator leads is assessed radiographically during their percutaneous implantation for trial stimulation. Usually the C-arm is repositioned several times to allow imaging in different planes, which may extend the total duration of surgery. The study aimed to evaluate whether the concurrent intraoperative use of 2 C-arms could safely reduce the duration of surgery. MATERIALS: This retrospective study included cases of percutaneous implantation of a spinal cord stimulation (SCS) lead for trial neurostimulation between 2006 and 2011. The duration of the surgical intervention was recorded, along with the duration of the preparation stage in the operating room. In addition, total radiation exposure time per case was recorded. RESULTS: Ninety-four patients underwent percutaneous implantation of an SCS lead (72 thoracolumbar, 22 cervical). In 73 cases 2 C-arms were used, with 21 cases performed with a single C-arm. In both the cervical and thoracolumbar groups, a biplanar configuration was associated with significant reduction in the mean length of the surgical phase, by 29 minutes (P = 0.017) and 14 minutes, respectively (P = 0.016), albeit while increasing the duration of the preoperative preparation stage. There was no significant difference in the total duration in the operating room or in the total radiation exposure time between groups. CONCLUSIONS: Here we present a technical note on the use of a biplanar fluoroscopy configuration for percutaneous implantation of SCS leads. This arrangement correlated with a reduction in surgery duration without increasing total radiation exposure, representing a practical and safe adjustment to current practice.

Coherent anti-Stokes Raman scattering and two photon excited fluorescence for neurosurgery.

OBJECTIVE: There is no established method for in vivo imaging during biopsy and surgery of the brain, which is capable to generate competitive images in terms of resolution and contrast comparable with histopathological staining. METHODS: Coherent anti-Stokes Raman scattering (CARS) and two photon excited fluorescence (TPEF) microscopy are non-invasive all optical imaging techniques that are capable of high resolution, label-free, real-time, nondestructive examination of living cells and tissues. They provide image contrast based on the molecular composition of the specimen which allows the study of large tissue areas of frozen tissue sections ex vivo. RESULTS: Here, preliminary data on 55 lesions of the central nervous system are presented. The generated images very nicely demonstrate cytological and architectural features required for pathological tumor typing and grading. Furthermore, information on the molecular content of a probe is provided. The tool will be implemented into a biopsy needle or endoscope in the near future for in vivo studies. CONCLUSION: With this promising multimodal imaging approach the neurosurgeon might directly see blood vessels to minimize the risk for biopsy associated hemorrhages. The attending neuropathologist might directly identify the tumor and guide the selection of representative specimens for further studies. Thus, collection of non-representative material could be avoided and the risk to injure eloquent brain tissue minimized.

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.

Multifocal glioblastoma multiforme in the posterior fossa mimicking cerebral metastases: case presentation and review of the current literature.

OBJECTIVE: In general, glioblastomas multiforme (GBM) arise in the supratentorial region, but in less than 4% of cases they also occur in the posterior fossa, particularly in the cerebellum. Furthermore, a minority of malignant gliomas are multifocal. We report on an unusual case with infratentorial multifocal lesions, suspicious for metastases, which turned out to be a multifocal GBM of the posterior fossa. PATIENT AND METHOD: A 69-year-old woman presented with recurring episodes of vertigo, headache, and progressive weight loss. Three multifocal cerebellar and brainstem lesions highly suspicious for metastases were identified by magnetic resonance imaging (MRI). Workup for malignancy elsewhere in the body was negative. RESULTS: The patient underwent craniotomy with successful resection of the tumor in the cerebellar vermis with an excellent outcome and uneventful postsurgical course. Histopathology of the tumor revealed features consistent with the diagnosis of GBM and ruled out metastatic lesions. Workup for molecular genetics characterized this tumor as a primary GBM. The patient initially responded to treatment with radiation therapy and temozolomide but died after 10 months with a tumor relapse. CONCLUSION: We discuss the unusual aspects of multifocal primary GBMs in the posterior fossa. Although rare, they should be considered in the differential diagnosis of cerebellar tumors, which stresses the importance of a surgical treatment to establish a histological diagnosis because there are no reliable radiographic criteria for distinguishing multifocal infratentorial gliomas from multiple metastases and other tumor entities. The differentiation between a primary and secondary cerebellar GBM did not lead to any change of the treatment strategy in this case.

Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats.

BACKGROUND: Vagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear. METHODS: Bilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research. We studied the effects of vagus nerve stimulation (VNS) on disturbed one-way active avoidance learning and neurogenesis in the hippocampal dentate gyrus of rats. RESULTS: After a stimulation period of 3 weeks, OBX rats acquired the learning task as controls. In addition, the OBX-related decrease of neuronal differentiated BrdU positive cells in the dentate gyrus was prevented by VNS. CONCLUSIONS: This suggests that chronic VNS and changes in hippocampal neurogenesis induced by VNS may also account for the amelioration of behavioral deficits in OBX rats. To the best of our knowledge, this is the first report on the restorative effects of VNS on behavioral function in an animal model of depression that can be compared with the effects of antidepressants.

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.

Advances in optical biopsy--correlation of malignancy and cell density of primary brain tumors using Raman microspectroscopic imaging.

Raman spectroscopy is a promising tool towards biopsy under vision as it provides label-free image contrast based on intrinsic vibrational spectroscopic fingerprints of the specimen. The current study applied the spectral unmixing algorithm vertex component analysis (VCA) to probe cell density and cell nuclei in Raman images of primary brain tumor tissue sections. Six Raman images were collected at 785 nm excitation that consisted of 61 by 61 spectra at a step size of 2 micrometers. After data acquisition the samples were stained with hematoxylin and eosin for comparison. VCA abundance plots coincided well with histopathological findings. Raman spectra of high grade tumor cells were found to contain more intense spectral contributions of nucleic acids than those of low grade tumor cells. Similarly, VCA endmember signatures of Raman images from high grade gliomas showed increased nucleic acid bands. Further abundance plots and endmember spectra were assigned to tissue containing proteins and lipids, and cholesterol microcrystals. Since no sample preparation is required, an important advantage of the Raman imaging methodology is that all tissue components can be observed - even those that may be lost in sample staining steps. The results demonstrate how morphology and chemical composition obtained by Raman imaging correlate with histopathology and provide complementary, diagnostically relevant information at the cellular level.

Interpreting CARS images of tissue within the C-H-stretching region.

Single band coherent anti-Stokes Raman scattering (CARS) microscopy is one of the fastest implementation of nonlinear vibrational imaging allowing for video-rate image acquisition of tissue. This is due to the large Raman signal in the C-H-stretching region. However, the chemical specificity of such images is conventionally assumed to be low. Nonetheless, CARS imaging within the C-H-stretching region enables detection of single cells and nuclei, which allows for histopathologic grading of tissue. Relevant information such as nucleus to cytoplasm ratio, cell density, nucleus size and shape is extracted from CARS images by innovative image processing procedures. In this contribution CARS image contrast within the C-H-stretching region is interpreted by direct comparison with Raman imaging and correlated to the tissue composition justifying the use of CARS imaging in this wavenumber region for biomedical applications.

Palliative considerations in the surgical treatment of spinal metastases: evaluation of posterolateral decompression combined with posterior instrumentation.

PURPOSE: To evaluate the outcome of patients with spinal metastases, treated under palliative considerations by spinal decompression and sole posterior instrumentation, in respect to survival, neurological symptomatology, pain, ECOG grade, and Tomita's prognostic score (TPS). PATIENTS AND METHODS: Fifty-seven consecutive patients with metastatic vertebral tumors were treated using a posterolateral approach for decompression combined with posterior instrumentation. Mean age was 58.6 years. In average, 3.4 vertebral segments were involved in instrumentation. RESULTS: Preoperative mean TPS was 5.9. The majority of the patients (70.2%) presented with an ECOG grade ≤2. The distribution of the metastatic lesions that needed surgical treatment was: 7.8% cervical, 60.9% thoracical, and 31.3% lumbar. In 52.6% the tumor led to pathological vertebral fractures. Mean pain VAS scores improved significantly in all but one patient from 6.6 preoperatively to 3.1 postoperatively. Post-surgical Frankel grades decreased. Mean postoperative survival was 11.4 months. Ten patients survived until now. Forty-seven patients have died with a mean survival of 9 months. Complication rate was only 5.3% with two superficial wound infections and one seroma. Not a single case of posterior spinal instrumentation fatigue failure was detected. CONCLUSIONS: Palliative surgical treatment for metastatic spinal tumors using a decompressive posterolateral approach combined with sole posterior instrumentation achieved convincing clinical results. All patients with intractable pain showed significant improvement postoperatively, and neurological deterioration was avoided. Since patients with spinal metastases enter the terminal stage of their disease, it is generally agreed that they require only palliative surgical treatments. Accordingly, spinal decompression and stabilization may be performed to improve the quality of the remaining life of cancer patients.

Nonlinear microscopy, infrared, and Raman microspectroscopy for brain tumor analysis.

Contemporary brain tumor research focuses on two challenges: First, tumor typing and grading by analyzing excised tissue is of utmost importance for choosing a therapy. Second, for prognostication the tumor has to be removed as completely as possible. Nowadays, histopathology of excised tissue using haematoxylin-eosine staining is the gold standard for the definitive diagnosis of surgical pathology specimens. However, it is neither applicable in vivo, nor does it allow for precise tumor typing in those cases when only nonrepresentative specimens are procured. Infrared and Raman spectroscopy allow for very precise cancer analysis due to their molecular specificity, while nonlinear microscopy is a suitable tool for rapid imaging of large tissue sections. Here, unstained samples from the brain of a domestic pig have been investigated by a multimodal nonlinear imaging approach combining coherent anti-Stokes Raman scattering, second harmonic generation, and two photon excited fluorescence microscopy. Furthermore, a brain tumor specimen was additionally analyzed by linear Raman and Fourier transform infrared imaging for a detailed assessment of the tissue types that is required for classification and to validate the multimodal imaging approach. Hence label-free vibrational microspectroscopic imaging is a promising tool for fast and precise in vivo diagnostics of brain tumors.

Neural cell adhesion molecule isoform 140 declines with rise of WHO grade in human gliomas and serves as indicator for the invasion zone of multiform glioblastomas and brain metastases.

PURPOSE: Gliomas are highly invasive neuroepithelial tumors with a propensity of malignant transformation and very restricted treatment options. The neural cell adhesion molecule (NCAM) modulates cellular migration, proliferation, and synaptic plasticity by homophilic and heterophilic interactions. Hereby, we investigated its relevance as a glioma tissue marker for the biological aggressiveness of these tumors and compared these features with the carcinoma brain metastasis invasion zone. MATERIALS AND METHODS: We analyzed 194 human brain samples. Human tumor-free brain specimens served as control for the white and gray matter. In addition to that, we used human glioblastomas from nude rats. All tissues were investigated immunohistochemically for the expression of the NCAM isoform 140. Additionally, the multiplanar MRI-CT fusion neuronavigation-guided serial stereotactic biopsy was performed and completed by histopathological workup. RESULTS: Human gliomas loose NCAM-140 with the rise of their WHO grade. Meningiomas are NCAM-140 negative. As the most striking feature, human brain metastases and the majority of human glioblastomas of our patients and of nude rats were totally NCAM-140 negative. This NCAM negativity led us to the conclusion of three different main glioblastoma invasion patterns. Surprisingly, the majority of brain metastasis samples that contained surrounding brain parenchyma demonstrated invasive tumor cell nests beyond the sharply demarcated metastasis border. We also found invasive metastatic cell nests outside the contrast enhancing tumor zone by means of the MRI-CT fusion neuronavigation-guided serial stereotactic biopsy. CONCLUSION: The expression of NCAM-140 inversely correlates with the WHO grade of human gliomas. The lost expression of NCAM-140 in human glioblastomas and in brain metastases enables the investigation of the brain-tumor interface and the definition of glioblastoma invasion patterns and shows that brain metastases are more invasive than ever thought.

Cerebral metastasis of a primary heart sarcoma.

Primary cardiac sarcomas are exceptionally rare tumours. A brain metastasis of a primary cardiac sarcoma has never been reported before. Although we know lots of primary malignomas spreading to the brain, we never observed cerebral metastases of an atrial spindle cell sarcoma. Cardiac sarcomas are more likely to haematogenously metastasize to the lung or the liver. Here, we describe the case of a young man, who suffered from a cerebral metastasis of a spindle cell sarcoma in the left heart atrium nine years ago. Postoperative whole brain irradiation with 30 Gy was performed. Later on, the patient experienced a local recurrence within the left atrium accompanied by cardiac arrhythmia and mitral valve insufficiency. This case is the very first description of a true cerebral metastasis from a primary heart sarcoma. Therefore, clear treatment paradigms are not established. Further case illustrations and the publication of larger patient series are mandatory, whenever possible.

PEEK cages as a potential alternative in the treatment of cervical spondylodiscitis: a preliminary report on a patient series.

The surgical management of cervical spondylodiscitis consists of the resection of the affected disc, the decompression of the cervical spinal cord, followed by the stabilization using an autologous bone graft or a titanium implant combined with a ventral plate fixation. Until now, there were no studies about the practicability and putative safety of PEEK cages in cervical spine infection. Now, we present the history of five patients suffering from neurological deficits and septicemia caused by mono- or bisegmental pyogenic cervical discitis and intraspinal abscess without severe bone destruction. Patients were treated surgically by discectomy, decompression, and ventral spondylodesis. The disc was replaced by a PEEK cage without additional fixation. Progressive bony fusion and complete regression of the inflammatory changes was demonstrated 7-8 months later by a computer assisted tomography and contrast enhanced magnetic resonance imaging, respectively. The vertebral alignment changed minimally; the cages developed only a slight average subsidence. The clinical symptoms improved in all patients significantly. Neck pain or instability was never observed. Nevertheless, prospective investigations of a larger patient series are mandatory. We suppose that the use of PEEK cages represents a potential and safe alternative in the treatment of cervical spondylodiscitis in selected patients.

Glioblastoma cells express functional cell membrane receptors activated by daily used medical drugs.

PURPOSE: Calcium ions are highly versatile spacial and temporal intracellular signals of non-excitable cells and have an important impact on nearly every aspect of cellular life controlling cell growth, metabolism, fluid secretion, information processing, transcription, apoptosis, and motility. Neurons and glia respond to stimuli, including neurotransmitters, neuromodulators, and hormones, which increase the intracellular calcium concentration. The function of intracellular calcium in gliomas is unknown. Lots of daily used drugs may act via receptors that can be linked to the intracellular calcium system and therefore could influence glioma biology. METHODS: Glioma cells were loaded with the calcium ion sensitive dye Fura 2-AM. Subsequently, cells were stimulated with 25 different medical drugs for 30 s. The increase of free intracellular calcium ions was measured and calculated by a microscope-camera-computer-unit. RESULTS: Except for the buffer solution HEPES that served as negative control and for the cortisol derivative dexamethasone, all other 24 tested drugs induced a rise of intracellular calcium ions. The cellular calcium responses were classified into seven functional groups. The tested substances activated several types of calcium channels and receptors. CONCLUSIONS: Our study impressively demonstrates that medical drugs are potent inducers of intracellular calcium signals. Totally unexpected, the results show a high amount of functional cellular receptors and channels on glioma cells, which could be responsible for certain biological effects like migration and cell growth. This calcium imaging study proves the usability of the calcium imaging as a screening system for functional receptors on human glioma cells.

Metastatic glioblastoma cells use common pathways via blood and lymphatic vessels.

Generally, gliomas do not metastasize. Therefore, larger series are not available to investigate the pathways of tumour spread. Here, we present the case of a young man with a glioblastoma multiforme WHO grade IV and distant metastases in several tissues. The glioblastoma multiforme WHO grade IV of a young male patient recurred within a very short time along the surgical resection pathway within the temporalis muscle. After removal of the tumour bulk, the patient developed a distant intracranial tumour lesion around the contralateral ventricular system and a pulmonary tumour. Later on, the patient underwent an operation on a facial lesion representing a local extracranial glioblastoma recurrence and containing metastases within lymph nodes and lymphatic vessels. Our case report indicated a lymphatic pathway of metastasis, which could be demonstrated by our histopathological analysis. We suggest that altered gene expression stimulated by glioblastoma-environment interaction altered the properties of glioblastoma cells, whether caused by a spontaneous genetic shift or induced by factors provided by the extracranial tissue.

Multiplanar MRI-CT fusion neuronavigation-guided serial stereotactic biopsy of human brain tumors: proof of a strong correlation between tumor imaging and histopathology by a new technical approach.

PURPOSE: Serial stereotactic biopsy is a diagnostic procedure, used when open biopsy or tumor bulk removal seems to be associated with a too high risk of new neurological deficits in tumors of eloquent regions or tumors of deep localizations or in anticipated high surgery related morbidity even in the older patient group. Shortcomings of this method are recognized to be the missed pathohistological information from untargeted areas in heterogeneous tumors. This study shows for the first time a collection of patients with brain tumors with their associated multiplanar MRI-CT fusion imaging during stereotaxis and the histopathological features of serial tumor biopsies along exact trajectorial sites towards the tumor center. METHODS: Thirteen patients were included. Stereotactic biopsy was performed and neuronavigation was correlated to histopathological features. RESULTS: Reactive tissue, endothelial hyperplasia, and diffusely scattered tumor cells occur outside the contrast-enhancing tumor in glioblastomas. Within the contrast-enhancing area, endothelial hyperplasia and diffuse tumor tissue were seen as compared to endothelial proliferations and the dense tumor as well as necroses in the image-defined center. CONCLUSIONS: Serial stereotactic biopsy is a reliable means. Strong correlations with the imaging characteristics of the lesions could be evaluated.