Optical requirements on magnification systems for intracranial video microsurgery.

INTRODUCTION: The basic idea of video-microsurgery is the improvement of ergonomic conditions in microsurgical procedures by replacing the bulky operating microscope with a compact videosystem. OBJECTIVE: To specify optical requirements on a videosystem for microsurgical intracranial procedures in neurosurgery. METHODS: During 27 microsurgical intracranial procedures (12 cerebellopontine angle and 15 supratentorial) zoom factor, focus distance and illumination parameters of the operating microscope were continuously recorded. Ergonomic aspects were documented as well. RESULTS: The zoom factor ranged from 1.7 to 13.5 in CPA procedures and from 1.4 to 13.4 in supratentorial procedures. The focus distance ranged from 180 mm to 367 mm in CPA procedures and from 188 mm-472 mm in supratentorial procedures. CONCLUSION: From an optical point of view current operating microscopes meet the requirements of intracranial microneurosurgery. However, ergonomically further developments are highly desirable. Video microsurgery is a promising field and could hold a solution to this problem.

Specific intensity imaging for glioblastoma and neural cell cultures with 5-aminolevulinic acid-derived protoporphyrin IX.

The fluorescence of protophorphyrin IX (PpIX) synthesized after incubation with 5-aminolevulinic acid (5-Ala) is used for the intraoperative visualisation of glioma cells in vivo. Such fluorescence may also be useful for the photodynamic therapy (PTD) of gliomas. A significant difference of fluorescence intensity in tumor cells compared to neurons is required for this application. To explore this, eight human glioma cell lines (LN-18, LN-428, U87MG, U373MG, D247MG, U251MG, LN-308, T98G) were compared with human astrocytes (SV-FHAS) and rat neurons after incubation for different periods of time in vitro with 5-Ala (1 mg/ml). Fluorescence intensity profiles were measured by a digital camera comparing glioma cell lines with control cells. All glioma cell lines could be discriminated from neural cells by their intensity of fluorescence by post-hoc tests for pairwise comparisons using Tukey's honestly significant difference test, at the global significance level of 5%. The glioma cell lines showed significant variation in this possibly limiting clinical use of fluorescence as a guide for resection.

P-glycoprotein and multidrug resistance-associated protein mediate specific patterns of multidrug resistance in malignant glioma cell lines, but not in primary glioma cells.

Understanding and overcoming multidrug resistance (MDR) may be a promising strategy to develop more effective pharmacotherapies for malignant gliomas. In the present study, human malignant glioma cell lines (n=12) exhibited heterogeneous mRNA and protein expression and functional activity of the mdr gene-encoded P-glycoprotein (PGP) and MDR-associated protein (MRP). Correlation between mRNA expression, protein levels and functional activity was strong. Inhibition of PGP activity by verapamil or PSC 833 enhanced the cytotoxic effects of vincristine, doxorubicin, teniposide and taxol. Inhibition of MRP activity by indomethacin or probenecid enhanced the cytotoxic effects of vincristine, doxorubicin and teniposide. The human cerebral endothelial cell line, SV-HCEC, exhibited the strongest PGP activity of all cell lines. Five primary human glioblastomas and one anaplastic astrocytoma displayed heterogenous protein levels of PGP and MRP-1 in tumor cells and of PGP in biopsy specimens in vivo, but no functional activity of these proteins upon ex vivo culturing. These data suggest that the glioma cell line-associated MDR-type drug resistance is a result of long-term culturing and that cerebral endothelial, but not glioma cells, may contribute to MDR-type drug resistance of gliomas in vivo.

Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme.

In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB). During inflammation, BBB properties are frequently lost, resulting in brain edema. To investigate whether BBB leakiness correlates with molecular changes at BBB TJs, we performed immunofluorescence stainings for TJ molecules in a mouse model of experimental autoimmune encephalomyelitis (EAE) and in human tissue with glioblastoma multiforme (GBM). In TJs of healthy CNS vessels in both mouse and man we detected occludin, ZO-1, claudin-5 and claudin-3. In EAE brain and spinal cord sections we observed the selective loss of claudin-3 immunostaining from TJs of venules surrounded by inflammatory cuffs, whereas the localization of the other TJ proteins remained unchanged. In addition, selective loss of claudin-3 immunostaining was also observed in altered cerebral microvessels of human GBM. Our data demonstrate the selective loss of claudin-3 from BBB TJs under pathological conditions such as EAE or GBM when the integrity of the BBB is compromised, and therefore suggest that claudin-3 is a central component determining the integrity of BBB TJs in vivo.

Influence of geometric and hemodynamic parameters on aneurysm visualization during three-dimensional rotational angiography: an in vitro study.

BACKGROUND AND PURPOSE: Aneurysm depiction with three-dimensional (3D) rotational angiography is influenced by investigator-defined parameters such as image acquisition and contrast agent injection and by the hemodynamic pattern in the parent artery and aneurysm. To assess the impact of the geometric configuration of parent artery and aneurysm on the 3D visualization of saccular aneurysms, we studied silicone aneurysm models under pulsatile-flow conditions. METHODS: Rotational angiography was performed in three bifurcation and three lateral aneurysm models with ostia of different widths. Three acquisition modalities (5, 8, and 14 seconds in duration, acquisition rate of 10 frames per second) and two techniques for the injection of contrast material (continuous flow and injection with an initial bolus) were applied. 3D reconstructions were obtained with a volume-rendering technique. RESULTS: Bifurcation aneurysms were visualized with high accuracy. Filling deficits distant to the inflow zone could be compensated for with the bolus-injection technique, and complete depiction of aneurysm shape was achieved in the 8-second rotation with 20 mL of contrast agent. In lateral aneurysms, the accuracy of 3D reconstructions depended on the width of the ostium. Although rotational studies in wide-necked lateral aneurysms yielded adequate reconstructions, 3D visualization of small-necked aneurysms was incomplete with the preferential depiction of the distal shell, which represents the inflow zone into the aneurysmal lumen. CONCLUSION: Contrast agent injection with the initial-bolus technique improved the depiction of aneurysms, compared with the continuous-flow method. Reconstructions of rotational studies of narrow-necked lateral aneurysms yielded incomplete visualization of the aneurysm.

Combining MEG and MRI with neuronavigation for treatment of an epileptiform spike focus in the precentral region: a technical case report.

BACKGROUND: Epileptic foci are often located in the vicinity but not necessarily within the boundaries of intra-axial brain tumors. Resection of these tumors is based on two major goals: first, maximizing tumor removal without provoking new neurologic deficits, and second, minimizing epileptic seizure activity. Magnetic source imaging (MSI) depicts the generators of magnetic fields overlaid on individual magnetic resonance (MR) images. Established application areas are lesions located adjacent to or partly within the sensory and motor cortex, or in the depth of the brain, necessitating a surgical approach through functionally highly relevant cortical regions. Magnetoencephalography (MEG) is also applicable for epileptiform spike foci recording during interictal activity. CASE DESCRIPTION: A patient with a recurrent glioma close to the Rolandic cortex scheduled for epilepsy and tumor surgery was investigated with MSI. The MSI data showed an epileptiform spike focus outside the tumor boundaries. The resulting MSI images were integrated into our neuronavigation system. This procedure allowed for the preoperative identification of the sensory and motor cortex, the precise localization of the epileptiform spike focus, and careful planning of the surgical procedure. In this case, we were able to safely resect the recurrent tumor and the epileptiform spike focus under general anesthesia using MSI-based neuronavigational guidance but no conventional intraoperative mapping techniques. CONCLUSION: Magnetic source imaging can be a valuable, noninvasive method for planning and performing tumor resections in high-risk brain regions, especially if an epileptiform spike focus has to be localized and included into the resection strategy.

Neoadjuvant gemcitabine/treosulfan chemotherapy for newly diagnosed glioblastoma: a phase II study.

The median survival for patients with glioblastoma is 12 months. The authors evaluated whether preirradiation gemcitabine/treosulfan (GeT) chemotherapy followed by standard radiotherapy improved outcome in patients with glioblastoma. Seventeen patients with newly diagnosed glioblastoma were enrolled in a prospective, unicenter trial of preirradiation GeT chemotherapy. Chemotherapy included up to 4 cycles of intravenous gemcitabine (1000 mg/m2 body surface) and treosulfan (3500 mg/m2 body surface) on days 1 and 8 of 28 days treatment cycles. Involved field radiotherapy (60 Gy in 30 fractions) was given after chemotherapy or earlier in the case of disease progression or drug intolerance. There was no specific treatment-related neurotoxicity reported, but in 3 of 17 patients (18%) chemotherapy was stopped because of World Health Organization (WHO) IV hematological toxicity. With GeT chemotherapy alone, there was a median progression-free survival of 12 weeks and a progression-free survival rate at 4 months of 29%. In 16 of 17 patients who subsequently received a full course of radiotherapy, the median progression-free survival from the time of diagnosis was 8 months, and the progression-free survival rate at 12 months was 25% (4 of 16 patients). The median overall survival was 12 months. Neither age nor extent of the residual postoperative tumor predicted the duration of progression-free survival after chemotherapy alone or after chemotherapy followed by radiotherapy. The combination of gemcitabine and treosulfan produced significant hematological toxicity in patients with newly diagnosed glioblastoma. The schedule used in the present study did not confer any significant survival advantage compared with standard involved field radiotherapy alone.

Simultaneous virtual representation of both vascular and neural tissue within the subarachnoid space of the basal cistern--technical note.

BACKGROUND: The representation of different anatomical structures requires varying imaging modalities and protocols. By mental composition of single-slice images, a three-dimensional (3D) impression can be achieved. However, this presupposes an outstanding imagination and is subject to inaccuracies. The use of an interactive and multi-modal planning system which represents different data sets in one single virtual environment holds promise to facilitate and improve neurosurgical decision-making. The authors report the clinical application of a self-developed virtual planning system in a case of trigeminal neuralgia due to an ectatic basilar artery. MATERIAL/METHODS: We modified our virtual planning system (VIVENDI), to achieve a virtual representation of the basal cistern illustrating both vascular and neuronal information. After conducting several experiments to determine an appropriate scanning protocol, we matched the data achieved by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). RESULTS: The system provides the vascular topography combined with information on the anatomical structure of the subarachnoid space. To illustrate the clinical usefulness of this planning approach, the authors present a case of trigeminal neuralgia caused by an ectatic basilar artery. Pre-operatively, the virtual representation returned accurate information on the anatomical configuration of the cerebellopontine angle and the course of the ectatic vessel. This information was confirmed during surgery. CONCLUSIONS: The presented case demonstrates the clinical applicability of VIVENDI within the subarachnoid space of the basal cistern. The virtual representation enables pre-operative planning and simulation based on the patient's individual anatomy.

Novel multipurpose bipolar instrument for endoscopic neurosurgery.

OBJECTIVE: Hemorrhage control in endoscopic neurosurgery is critical because of the lack of suitable instruments for coagulation. One reason for this problem is that miniaturization of the instruments is still a technical problem. In this article, we present a solution: the use of bipolar microforceps with a small diameter of 1.5 mm. METHODS: With the use of modern synthetic and metallic materials, the construction of the bipolar microforceps was designed without the use of mechanical joints. All movable elements are integrated within the instrument shaft. This design provides optimal visibility of the operating field because the sheath has a diameter of only 1.5 mm along its entire length. Therefore, this instrument is compatible with most working channels of neuroendoscopes. RESULTS: The new, joint-free design of the forceps and the electric insulation of the branches were the technical innovations that led to the development of this novel, multipurpose instrument. CONCLUSION: This new instrument may enhance endoscopic resection and shrinkage of cystic lesions and may offer new possibilities in endoscopic tumor resection and the treatment of hemorrhage.

Extracellular matrix and the blood-brain barrier in glioblastoma multiforme: spatial segregation of tenascin and agrin.

The quality of the blood-brain barrier (BBB), represented mainly by endothelial tight junctions (TJ), is now believed to be dependent on the brain microenvironment and influenced by the basal lamina of the microvessels. In the highly vascularized glioblastoma multiforme (GBM), a dramatic increase in the permeability of blood vessels is observed but the nature of basal lamina involvement remains to be determined. Agrin, a heparan sulfate proteoglycan, is a component of the basal lamina of BBB microvessels, and growing evidence suggests that it may be important for the maintenance of the BBB. In the present study, we provide first evidence that agrin is absent from basal lamina of tumor vessels if the TJ molecules occludin, claudin-5 and claudin-1 were lacking in the endothelial cells. If agrin was expressed, occludin was always localized at the TJ, claudin-5 was frequently detected, whereas claudin-1 was absent from almost all vessels. Furthermore, despite a high variability of vascular phenotypes, the loss of agrin strongly correlated with the expression of tenascin, an extracellular matrix molecule which has been described previously to be absent in mature non-pathological brain tissue and to accumulate in the basal lamina of tumor vessels. These results support the view that in human GBM, BBB breakdown is reflected by the changes of the molecular compositions of both the endothelial TJ and the basal lamina.

Radiosurgery for brain metastases: the Tuebingen experience.

PURPOSE: To retrospectively investigate the effectiveness of linear accelerator based radiosurgery (RS) in the treatment of brain metastases (BM). MATERIAL AND METHODS: Of 55 patients with a total of 72 BM, 41 patients had a single brain metastasis and 14 patients had two or three metastases. Median tumour dose of 15Gy (range 8-20Gy) was prescribed to a median isodose surface of 90% (range 70-100%) encompassing the target volume. RESULTS: The median survival time (MST) for all 55 patients was 7 months [95% confidence interval (CI), 5-10 months] and 2-year survival is 18%. There was no significant difference between patients who had one brain metastasis and those with either two or three metastases (log rank P=0.7565). Multivariate analysis in patients with a single BM showed that interval between primary diagnosis (PD) to BM, maximum size of metastasis, and histology (renal cell carcinoma and melanoma versus others) were independent prognostic factors influencing survival. Local control was obtained in 66/72 (92%) metastases. Actuarial local control at 24 months was 52%. Only age (50 years) and histology (renal cell versus others) influenced local control in the univariate analysis in patients with a single BM. In multivariate analysis, size, histology (renal cell and melanoma versus others), activity of extracranial metastatic disease, age, interval from PD to BM and location (midline versus other) independently influenced local control, while the dose was not significant for our patient group. Only one patient developed radiographically suspected RS-induced necrosis after previous whole brain RT. CONCLUSION: RS was effective and little toxic in BM. Identification of prognostic factors must be performed to gain knowledge on patients most likely to benefit from this procedure.

Neuroendoscopic treatment of idiopathic occlusion of the foramen of Monro in adults--two case reports.

Two adults presented with hydrocephalus due to idiopathic obstruction of the bilateral foramina of Monro, manifesting as clinical signs of chronically elevated intracranial pressure. No inflammation was present. The primary surgical treatment was neuroendoscopic reconstruction of the right foramen of Monro. A 37-year-old man had a spontaneous perforation of the septum pellucidum. The patient required a ventriculoperitoneal shunt, although postoperative ventriculography proved free passage of cerebrospinal fluid from the lateral ventricle into the third ventricle. A 62-year-old man underwent additional septostomy and third ventriculostomy, and the neuroendoscopic intervention relieved the presenting symptoms without additional treatment. The biopsy specimens showed no evidence of malignancy in either case. Neuroendoscopic intervention is an alternative treatment in the management of hydrocephalus due to idiopathic obstruction of the foramen of Monor. The procedure is less invasive than open microsurgical reconstruction and can even avoid ventriculoperitoneal or ventriculoatrial shunting.

Subdural hygroma as a complication of endoscopic neurosurgery--two case reports.

Two cases of subdural hygroma occurred in a series of 77 neuroendoscopic procedures. An 8-year-old boy underwent neuroendoscopic cysto-cisternostomy of a left temporal arachnoid cyst. Routine postoperative magnetic resonance imaging 7 days later showed a large left-sided subdural hygroma without clinical symptoms. During the following 3 months, the subdural hygroma did not resolve spontaneously, so it was drained through a burr hole. A 3-month-old boy with aqueductal stenosis developed bilateral subdural hygromas after third ventriculostomy. Several punctures through the open anterior fontanelle relieved the hygromas but increasing head circumference required ventriculoperitoneal shunting 12 months later. Complications of neuroendoscopic procedures are increasingly reported, including various kinds of bleeding, infections, or damage of neuronal tissue. Only three previous cases of subdural hygroma or hematoma after neuroendoscopic interventions have been reported. The possible etiologies and clinical consequences of this rare complication have to be considered before selecting neuroendoscopy treatment.