Access to Meckel's cave for biopsies of indeterminate lesions: a systematic review.

Accessing Meckel's cave (MC) is surgically challenging. Open approaches are complex and often correlated with high morbidity. Endoscopic approaches emerged in the last decade as feasible alternatives to open approaches, especially for sampling indeterminate lesions. This article first analyses available routes to approach Meckel's cave and presents furthermore an illustrative case. We conducted a systematic review and reported according to the guidelines for preferred reporting items for systematic reviews and meta-analyses (PRISMA). Various surgical approaches identified through the search are evaluated and discussed in detail. Additionally, we report on a case of woman with a lesion in MC, which was accessed through an endoscopic transpterygoid approach subsequently diagnosed as a diffuse large B cell lymphoma. Our search delivered 75 articles that included case reports (n = 21), cadaveric studies (n = 32), clinical articles (n = 16), review of the literatures (n = 3), as well as technical notes (n = 2) and a radiological manuscript (n = 1). Open routes included lateral approaches with many variations, mainly intra- and extradural pterional approaches and anterior petrosal, as well as a retrosigmoid intradural suprameatal and a lateral transorbital approach. Endoscopically, MC was reached via approaches that included transpterygoid, transorbital or infraorbital fissure routes. Percutaneous approaches, e.g. through the foramen ovale, were also described. Multiple surgical approaches to MC are currently available. Their different characteristics as well as individual patient factors, such as clinical history and the localization of the disease, have to be considered when choosing a surgical corridor. Studies included in this review highlight the endonasal endoscopic transpterygoidal technique as an excellent corridor for biopsies in the ventral MC.

Risk-assessment in chronic subdural hematoma evaluated in 148 patients - A score for predicting recurrence.

BACKGROUND: Chronic subdural hematoma (CSDH) is a frequent disease in neurosurgical practice. However, a considerable recurrence rate keeps this condition challenging to treat. We aimed to provide a simple tool for risk assessment in these patients. METHODS: We conducted a retrospective analysis of surgically treated patients with chronic subdural hematomas. In addition to patients' demographics, radiological assessment included volume, thickness, midline shift and density of hematomas. Statistically significant variables in univariate analysis were further analyzed in a multivariate logistic regression model to create a risk score for recurrence of CSDH. RESULTS: A total of 148 patients were identified and included for analysis. 50.7 % (n = 75) were older than 76 years of age. The overall hematoma recurrence rate requiring surgery was 23.6 % (n = 35). Preoperative thrombocytopenia, postoperative midline shift >6 mm, hematoma volume >80 mL and overall hematoma density >45 Hounsfield Units (HU), were significantly more frequent in the recurrence group. Furthermore, after multivariate assessment, postoperative hematoma density and volume were independent risk factors and included in the risk assessment tool. Patients were divided into 3 risk groups corresponding to the total scores. CONCLUSION: We provide a risk-score assessment for predicting recurrence of subdural hematoma. The risk-score comprises postoperative hematoma volume and density. This tool could ease decision making in follow-up evaluation and indication for recurrence surgery. Yet, further prospective evaluation is required to assess the clinical value of this tool.

Maximizing safe resections: the roles of 5-aminolevulinic acid and intraoperative MR imaging in glioma surgery-review of the literature.

Malignant glioma surgery involves the challenge of preserving the neurological status of patients harboring these lesions while pursuing a maximal tumor resection, which is correlated with overall and progression-free survival. Presently, several tools exist for assisting neurosurgeons in visualizing malignant tissue. Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) has increasingly been used during the last decade for identifying malignant glioma. Intraoperative magnetic resonance imaging (iMRI), first introduced in the mid-1990s, is being evaluated as a further tool to maximize the extent of resection. We aimed to evaluate the literature and discuss synergies and differences between FGS with 5-ALA and iMRI. We conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. After excluding non-relevant articles, 16 articles were evaluated and included in the qualitative analysis, comprising 2 (n = 2) reviews of the literatures, 1 (n = 1) book chapter, and 13 (n = 13) clinical articles. ALA-induced fluorescence goes beyond the borders of gadolinium contrast enhancement. Several studies stress the synergy between both tools, enabling increase in extent of resection. We point out advantages of combining both methods. iMRI, however, is not widely available, is expensive, and is not recommended as sole resection control tool in high-grade glioma. For these centers, FGS together with mapping and monitoring techniques, neuronavigation and, when needed, intraoperative ultrasound provides an excellent setting for achieving state-of-the-art gross total resection of high-grade gliomas.

Altered inhibition in the hippocampal neural networks after spreading depression.

Prolonged neuronal depression after spreading depression (SD) is followed by a late cellular and synaptic hyperexcitability. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent hippocampus to investigate the role of γ-aminobutyric acid (GABA)-mediated inhibition in the late hyperexcitable state of SD. The effect of KCl-induced negative DC potential shifts was investigated on extracellularly recorded paired-pulse depression (PPD) and bicuculline-induced afterdischarges as well as intracellularly recorded inhibitory post synaptic potentials (IPSPs) in the hippocampal CA1 area. The results revealed that SD decreased the degree of PPD, enhanced the number and duration of bicuculline-induced afterdischarges, and reduced the amplitude and duration of IPSPs. Application of low concentrations of bicuculline before the induction of SD enhanced the inhibitory effect of SD on IPSPs. Data indicate the contribution of GABA-mediated inhibition to SD-induced delayed hyperexcitability. Modulation of GABA function in the late hyperexcitability phase of SD may play a role in therapeutic management of SD-related neurological disorders.

Anatomic features of glioblastoma and their potential impact on survival.

BACKGROUND: Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells. In the present study, we examined different growth patterns and their possible relations to patient survival. METHODS: To analyze whether anatomical characteristics are related to prognosis, we reviewed the prospectively collected pre- and postoperative MRIs of 83 patients in the 5-ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized analytic work flow, the tumor volume and site, presence of necrosis or cysts, and perifocal edema were assessed preoperatively. In the same way, postoperative MRI and the MRI at first recurrence were analyzed. In addition, survival time of the patients was documented. RESULTS: Median survival time of all 83 patients was 15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as well as the presence of intratumoral necrosis or cysts, did not exert a significant effect on survival time; 96.4 % of recurrences occurred within the former resection margin. Tumors with initial contact with the subependymal zone had multifocal or ventricular recurrences significantly more often. In patients with residual tumor on early postoperative MRI, the follow-up images displayed enlargement of the remnants in 91.9 % of these cases. CONCLUSIONS: A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections.

[Interdisciplinary neuro-oncology: part 1: diagnostics and operative therapy of primary brain tumors]. / Interdisziplinäre Neuroonkologie : Teil 1: Diagnostik und operative Therapie primärer Gehirntumoren.

By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function is increasingly feasible. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

[Interdisciplinary neuro-oncology: part 2: systemic therapy of primary brain tumors]. / Interdisziplinäre Neuroonkologie : Teil 2: Systemtherapie primärer Gehirntumoren.

By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function has become dramatically more extensive. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro.

BACKGROUND: T-cell responses contribute to the anti-tumoural effect of photodynamic therapy (PDT). For such responses to occur, dendritic cells (DCs) have to migrate to the tumour, take up tumour antigens and respond to danger signals with maturation, before they engage in T-cell activation. Here, we have studied the effect of 5-aminolevulinic acid (ALA)-mediated PDT on DCs in vitro in a human spheroid model of glioblastoma (GB). METHODS: Spheroids of the GB cell lines U87 and U251 were treated with ALA/PDT, and effects on attraction, uptake of tumour antigens and maturation of DCs were studied. To block heat-shock protein-70 (HSP-70) on the spheroids, neutralising antibodies were used. RESULTS: 5-Aminolevulinic acid /PDT-treated GB spheroids attracted DCs that acquired tumour antigens from the spheroids effectively. Moreover, co-culture with ALA/PDT-treated spheroids induced DC maturation as indicated by the upregulation of CD83 and co-stimulatory molecules as well as increased T-cell stimulatory activity of the DCs. Heat-shock protein-70 was upregulated on the spheroids after ALA/PDT treatment. Uptake of tumour antigens and DC maturation induced by the ALA/PDT-treated spheroids were inhibited when HSP-70 was blocked. CONCLUSION: ALA/PDT treatment of glioma spheroids promotes the three initial steps of the afferent phase of adaptive immunity, which is at least partially mediated by HSP-70.

BRAF-KIAA1549 fusion transcripts are less frequent in pilocytic astrocytomas diagnosed in adults.

AIM: Duplication of 7q34 resulting in generation of BRAF-KIAA1549 fusion transcripts is a characteristic event in pilocytic astrocytoma that may also aid distinction from diffuse astrocytic tumours. As data on BRAF-KIAA1549 fusion transcript status remain mainly limited to children, we aimed to examine the diagnostic value of BRAF-KIAA1549 fusion transcripts across all age groups. METHODS: BRAF-KIAA1549 fusion transcript status was examined using reverse transcription polymerase chain reaction on formalin-fixed paraffin-embedded samples of 105 primary pilocytic astrocytomas [median patient age: 17 years (1-74 years)]. RESULTS: Informative results (distinct wildtype BRAF bands detectable) were obtained in 105/124 cases (85%). Fusion transcripts were detected in 53 of cases (51%). They were more often encountered in tumours of infratentorial location [42/67 (63%) vs. 11/38 (29%)] and comprised KIAA1549-Ex16_BRAF-Ex9 (32 cases), KIAA1549-Ex15_BRAF-Ex9 (14 cases) and KIAA1549-Ex16_BRAF-Ex11 (seven cases). Fusion transcripts were present in 79% of tumours diagnosed in the first decade of life, but only in 51% of patients aged 11-20 years, 42% of patients aged 21-30 years, 30% of patients aged 31-40 years and 7% of patients older than 40 years. On multivariate logistic regression analysis, the association of fusion transcript status and age was confirmed adjusting for tumour location (P = 0.006). CONCLUSIONS: The frequency of BRAF-KIAA1549 fusion transcripts is significantly lower in adult patients with pilocytic astrocytoma, weakening the sensitivity of this specific diagnostic marker in that age group.

Management of patients with low-grade gliomas - a survey among German neurosurgical departments.

BACKGROUND AND AIMS OF THE STUDY: The diagnosis and treatment of low-grade gliomas (LGG) are multimodal. Today, there is no defined standard in diagnosis and treatment. Controversies are, in general, about a "wait-and-see" strategy, diagnostic workup, surgical intervention, postoperative imaging, adjuvant treatment, and follow-up. The aim of this study is to gain an overview about management strategies of high-volume German neurosurgical departments treating these patients. MATERIAL AND METHODS: A questionnaire including diagnostic, preoperative, perioperative, and postoperative parameters and 5 cases with magnetic resonance imaging data with questions to various treatment options in these patients was sent to all 34 German neurosurgical departments at university hospitals. RESULTS: In total, 24 questionnaires were returned and analysed. Centres were divided into those who generally practice a "wait-and-see" strategy vs. those who do not or only in highly selected cases. Statistical analyses were performed with Fisher test and Chi (2)-test. Interestingly, 50% of all centres routinely follow a "wait-and-see" strategy. CONCLUSION: Although the management of patients with LGG is complex and a simple questionnaire will not be able to define a standard in diagnosis and treatment, this study offers an overview on strategies at high-volume academic centres dealing with these patients. There is consensus to resect superficially located lobar and circumscribed low-grade lesions. However, the differences between centres become apparent with increasing complexity of the lesions.

Specific biomarkers of receptors, pathways of inhibition and targeted therapies: clinical applications.

A deeper understanding of the role of specific genes, proteins, pathways and networks in health and disease, coupled with the development of technologies to assay these molecules and pathways in patients, promises to revolutionise the practice of clinical medicine. In particular, the discovery and development of novel drugs targeted to disease-specific alterations could benefit significantly from non-invasive imaging techniques assessing the dynamics of specific disease-related parameters. Here we review the application of imaging biomarkers in the management of patients with brain tumours, especially malignant glioma. This first part of the review focuses on imaging biomarkers of general biochemical and physiological processes related to tumour growth such as energy, protein, DNA and membrane metabolism, vascular function, hypoxia and cell death. These imaging biomarkers are an integral part of current clinical practice in the management of primary brain tumours. The second article of the review discusses the use of imaging biomarkers of specific disease-related molecular genetic alterations such as apoptosis, angiogenesis, cell membrane receptors and signalling pathways. Current applications of these biomarkers are mostly confined to experimental small animal research to develop and validate these novel imaging strategies with future extrapolation in the clinical setting as the primary objective.

[Local therapy of primary brain tumors]. / Lokale Therapien bei hirneigenen Tumoren.

In recent years further forms of local treatment for primary brain tumors have been developed in addition to resection and radiation. There are basically three principles for local therapy, intralesional therapy for primary or recurrent non-resectable tumors as well as intracavitary and pericavitary therapy following microscopic surgical complete resection. Local therapy procedures are complex and suffer from special difficulties in the evaluation of their effectiveness by imaging techniques, because they are inevitably accompanied by alterations in the imaging, barrier disturbances and contrast medium uptake.

[Modification of the retrolabyrinthine approach with hearing preservation in CPA tumors]. / Modifizierter retrolabyrinthärer Zugangsweg bei Kleinhirnbrückenwinkeltumoren zum Hörerhalt.

BACKGROUND: In an anatomical study including a CT scan of the cadaver sections by means of a virtual model analysis the option of a modified retrolabyrinthine passage to the cerebellopontine angle (CPA) preserving the Saccus endolymphaticus and the upper petrosus sinus was analysed. METHODS: Due to the individual anatomical variations of the petrosus bone the results showed several limitations with regard to the retrolabyrintine passage to the CPA. The smallest distance between the dura of the posterior fossa and the posterior semicircular canal measured in a high resolution CT was of particular importance as to how much room was available for the surgical manipulation in the retrolabyrinthine space. As the back side angle to the petrosus bone is much flatter in a translabyrinthine approach than in a retrosigmoidal approach the internal auditory canal needed to be controlled by using a 30 degree endoscope. RESULTS: In five patients the translabyrinthine approach was modified by temporarily preserving the labyrinth in an effort to remove the CPA tumors. Based on our clinical experience and on the findings of the anatomical and radiological studies we eventually removed the CPA tumors type B2 or C3 in three patients preserving hearing by using a modified retrolabyrinthine approach.

[Significance of emissary veins in surgical treatment of temporal paragangliomas]. / Stellenwert emissarischer Venen bei der operativen Therapie temporaler Paragangliome.

With the surgical removal of temporal paraganglioma, possible changes of the cerebral blood pathways of the Circle of Willis should be considered. If the cerebral blood drains dominates unilaterally and the pathway of drainage over the Bulbus venae jugularis is inadequate due to vessel malformation or variations or by intraluminal tumor growth, as for instance of temporal paragangliomas, collateral emissary vessels can take over this function by an extraordinary large lumen extension. Ignorance of such a characteristic venous drainage can lead to hemorrhagic apoplexia when such originally redundant veins are sacrificed. A presurgical angiography is, therefore, indicated. In case of vessel malformations or variations the use of computer-assisted surgery could be helpful to preserve such native emissary veins at the bony skull base, such as the condylar emissary vein in the case of a transcondylar infralabyrinthine approach.

Supratentorial meningeal melanocytoma mimicking a convexity meningioma.

OBJECTIVE AND IMPORTANCE: Meningeal melanocytomas are rare benign neuro-ectodermal tumors arising from melanocytic cells in the leptomeninges. These leptomeningeal melanocytes are found at highest density underneath the brain stem and along the upper cervical spinal cord. Thus, most reported cases of meningeal melanocytomas are located in the posterior fossa and the spinal cord, respectively. CLINICAL PRESENTATION: We report on the rare case of a 55-year-old male patient with a large supratentorial meningeal melanocytoma mimicking a convexity meningioma and a smaller, similarly dura based lesion in the posterior fossa. INTERVENTION: Tumor control to date was achieved by surgery of the large lesion and radiosurgery of the small lesion. CONCLUSION: Complete tumor resection may be advantageous and second or recurrent lesions may be managed by repeat surgery or stereotactic radiosurgery.

Measuring the angular dependent energy distribution of backscattered electrons at variable geometry.

An aluminium semisphere system with 120 points of entry and eight detection areas, assembled on a meridian covering 0.0026 steradian each, was put over a solid bulk sample (e.g., aluminium), which was mounted in the eucentric point so that the incident electron beam could be varied by a polar rotation of the sphere in steps of 11.25 degrees. The complete angular distribution of the backscattered electrons became available by a rotation in steps of 11.25 degrees azimuthally. For this particular setup, the signals from the detection areas as well as the signal from the rest of the semisphere were amplified by operational amplifiers (Burr-Brown OPA128LM). However the signal of the semisphere was not available at that time. Specimen current measurements made the total amount of electrons accessible, providing a possibility for normalization of the results and comparison with total backscattering coefficients. By use of counter voltage variable up to 10 kV inside the detection assembly, it was possible to measure an energy resolution of the backscattered electrons for each detection area at the same time. Details of the construction and calibration procedures, possible errors, and sources of systematic deviations as well as first test results are discussed.