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Objective: In times of the ubiquitous debate about doctors' working hour restrictions, it is still questionable if the physician's performance is impaired by high work load and long shifts. In this study, we evaluated the impact of sleep interruption on neurosurgical performance., Methods: Ten medical students and 10 neurosurgical residents were tested on the virtual-reality simulator NeuroTouch by performing an identical microsurgical task, well rested (baseline test), and after sleep interruption at night (stress test). Deviation of total score, timing, and excessive force on tissue were evaluated. In addition, vital parameters and self-assessment were analyzed., Results: After sleep interruption, total performance score increased significantly (45.1 vs. 48.7, baseline vs. stress test, P = 0.048) while timing remained stable (10.1 vs. 10.4 minutes for baseline vs. stress test, P > 0.05) for both students and residents. Excessive force decreased in both groups during the stress test for the nondominant hand (P = 0.05). For the dominant hand, an increase of excessive force was encountered in the group of residents (P = 0.05). In contrast to their results, participants of both groups assessed their performance worse during the stress test., Conclusions: In our study, we found an increase of neurosurgical simulator performance in neurosurgical residents and medical students under simulated night shift conditions. Further, microsurgical dexterity remained unchanged. Based on our results and the data in the available literature, we cannot confirm that working hour restrictions will have a positive effect on neurosurgical performance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Context: Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC., Case Description: Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A , suggesting a role of this gene in the pituitary adenoma development., Conclusion: PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients., (© 2017 European Society of Endocrinology.)

OBJECTIVE The authors' group recently published a novel technique for a navigation-guided frameless stereotactic approach for the placement of depth electrodes in epilepsy patients. To improve the accuracy of the trajectory and enhance the procedural workflow, the authors implemented the iSys1 miniature robotic device in the present study into this routine. METHODS As a first step, a preclinical phantom study was performed using a human skull model, and the accuracy and timing between 5 electrodes implanted with the manual technique and 5 with the aid of the robot were compared. After this phantom study showed an increased accuracy with robot-assisted electrode placement and confirmed the robot's ability to maintain stability despite the rotational forces and the leverage effect from drilling and screwing, patients were enrolled and analyzed for robot-assisted depth electrode placement at the authors' institution from January 2014 to December 2015. All procedures were performed with the S7 Surgical Navigation System with Synergy Cranial software and the iSys1 miniature robotic device. RESULTS Ninety-three electrodes were implanted in 16 patients (median age 33 years, range 3-55 years; 9 females, 7 males). The authors saw a significant increase in accuracy compared with their manual technique, with a median deviation from the planned entry and target points of 1.3 mm (range 0.1-3.4 mm) and 1.5 mm (range 0.3-6.7 mm), respectively. For the last 5 patients (31 electrodes) of this series the authors modified their technique in placing a guide for implantation of depth electrodes (GIDE) on the bone and saw a significant further increase in the accuracy at the entry point to 1.18 ± 0.5 mm (mean ± SD) compared with 1.54 ± 0.8 mm for the first 11 patients (p = 0.021). The median length of the trajectories was 45.4 mm (range 19-102.6 mm). The mean duration of depth electrode placement from the start of trajectory alignment to fixation of the electrode was 15.7 minutes (range 8.5-26.6 minutes), which was significantly faster than with the manual technique. In 12 patients, depth electrode placement was combined with subdural electrode placement. The procedure was well tolerated in all patients. The authors did not encounter any case of hemorrhage or neurological deficit related to the electrode placement. In 1 patient with a psoriasis vulgaris, a superficial wound infection was encountered. Adequate physiological recordings were obtained from all electrodes. No additional electrodes had to be implanted because of misplacement. CONCLUSIONS The iSys1 robotic device is a versatile and easy to use tool for frameless implantation of depth electrodes for the treatment of epilepsy. It increased the accuracy of the authors' manual technique by 60% at the entry point and over 30% at the target. It further enhanced and expedited the authors' procedural workflow.

Objectives: To investigate the value of local image variance (LIV) as a new technique for quantification of hypointense microvascular susceptibility-weighted imaging (SWI) structures at 7 Tesla for preoperative glioma characterization., Methods: Adult patients with neuroradiologically suspected diffusely infiltrating gliomas were prospectively recruited and 7 Tesla SWI was performed in addition to standard imaging. After tumour segmentation, quantification of intratumoural SWI hypointensities was conducted by the SWI-LIV technique. Following surgery, the histopathological tumour grade and isocitrate dehydrogenase 1 (IDH1)-R132H mutational status was determined and SWI-LIV values were compared between low-grade gliomas (LGG) and high-grade gliomas (HGG), IDH1-R132H negative and positive tumours, as well as gliomas with significant and non-significant contrast-enhancement (CE) on MRI., Results: In 30 patients, 9 LGG and 21 HGG were diagnosed. The calculation of SWI-LIV values was feasible in all tumours. Significantly higher mean SWI-LIV values were found in HGG compared to LGG (92.7 versus 30.8; p < 0.0001), IDH1-R132H negative compared to IDH1-R132H positive gliomas (109.9 versus 38.3; p < 0.0001) and tumours with significant CE compared to non-significant CE (120.1 versus 39.0; p < 0.0001)., Conclusions: Our data indicate that 7 Tesla SWI-LIV might improve preoperative characterization of diffusely infiltrating gliomas and thus optimize patient management by quantification of hypointense microvascular structures., Key Points: • 7 Tesla local image variance helps to quantify hypointense susceptibility-weighted imaging structures. • SWI-LIV is significantly increased in high-grade and IDH1-R132H negative gliomas. • SWI-LIV is a promising technique for improved preoperative glioma characterization. • Preoperative management of diffusely infiltrating gliomas will be optimized.

OBJECTIVE Robotic devices have recently been introduced in stereotactic neurosurgery in order to overcome the limitations of frame-based and frameless techniques in terms of accuracy and safety. The aim of this study is to evaluate the feasibility and accuracy of the novel, miniature, iSYS1 robotic guidance device in stereotactic neurosurgery. METHODS A preclinical phantom trial was conducted to compare the accuracy and duration of needle positioning between the robotic and manual technique in 162 cadaver biopsies. Second, 25 consecutive cases of tumor biopsies and intracranial catheter placements were performed with robotic guidance to evaluate the feasibility, accuracy, and duration of system setup and application in a clinical setting. RESULTS The preclinical phantom trial revealed a mean target error of 0.6 mm (range 0.1-0.9 mm) for robotic guidance versus 1.2 mm (range 0.1-2.6 mm) for manual positioning of the biopsy needle (p < 0.001). The mean duration was 2.6 minutes (range 1.3-5.5 minutes) with robotic guidance versus 3.7 minutes (range 2.0-10.5 minutes) with manual positioning (p < 0.001). Clinical application of the iSYS1 robotic guidance device was feasible in all but 1 case. The median real target error was 1.3 mm (range 0.2-2.6 mm) at entry and 0.9 mm (range 0.0-3.1 mm) at the target point. The median setup and instrument positioning times were 11.8 minutes (range 4.2-26.7 minutes) and 4.9 minutes (range 3.1-14.0 minutes), respectively. CONCLUSIONS According to the preclinical data, application of the iSYS1 robot can significantly improve accuracy and reduce instrument positioning time. During clinical application, the robot proved its high accuracy, short setup time, and short instrument positioning time, as well as demonstrating a short learning curve.

Bioimaging of brain tumors using nuclear medicine techniques complements computed tomography (CT) and magnetic resonance imaging (MRI), thus allowing more accurate diagnosis in clinically ambiguous situations. Special tracers for positron emission tomography (PET) have been developed which allow monitoring and planning of therapy. PET data may provide also presurgical evidence with regard to the presence of clinically relevant molecular brain tumor biomarkers. Combined PET/CT and PET/MR hybrid imaging systems will further enhance bioimaging-based brain tumor analysis. The main aim of brain tumor surgery is maximal safe tumor resection with preservation of neurologic functions, and to relieve tumor-related symptoms. In deep-seated unresectable tumors, diagnostic biopsy may be the main surgical goal. Special pre- and intraoperative techniques and approaches, including multidisciplinary team approaches, have been developed to optimize these surgical goals. Differences in spectrum, biology, and clinical presentation of brain tumors in the pediatric patient population demand special surgical expertise to warrant optimal postoperative patient outcome., (Copyright © 2017 Elsevier B.V. All rights reserved.)

OBJECTIVE One of the most important causes for recurrence of intracranial meningiomas is residual tumor tissue that remains despite assumed complete resection. Recently, intraoperative visualization of meningioma tissue by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence was reported. The aim of this study was to investigate the possible surgical benefits of PpIX fluorescence for detection of meningioma tissue. METHODS 5-ALA was administered preoperatively to 190 patients undergoing resection of 204 intracranial meningiomas. The meningiomas' PpIX fluorescence status, fluorescence quality (strong or vague), and intratumoral fluorescence homogeneity were investigated during surgery. Additionally, specific sites, including the dural tail, tumor-infiltrated bone flap, adjacent cortex, and potential satellite lesions, were analyzed for PpIX fluorescence in selected cases. RESULTS PpIX fluorescence was observed in 185 (91%) of 204 meningiomas. In the subgroup of sphenoorbital meningiomas (12 of 204 cases), the dural part showed visible PpIX fluorescence in 9 cases (75%), whereas the bony part did not show any PpIX fluorescence in 10 cases (83%). Of all fluorescing meningiomas, 168 (91%) showed strong PpIX fluorescence. Typically, most meningiomas demonstrated homogeneous fluorescence (75% of cases). No PpIX fluorescence was observed in any of the investigated 89 dural tails. In contrast, satellite lesions could be identified through PpIX fluorescence in 7 cases. Furthermore, tumor-infiltrated bone flaps could be visualized by PpIX fluorescence in all 13 cases. Notably, PpIX fluorescence was also present in the adjacent cortex in 20 (25%) of 80 analyzed cases. CONCLUSIONS The authors' data from this largest patient cohort to date indicate that PpIX fluorescence enables intraoperatively visualization of most intracranial meningiomas and allows identification of residual tumor tissue at specific sites. Thus, intraoperative detection of residual meningioma tissue by PpIX fluorescence might in future reduce the risk of recurrence.

OBJECT An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade. METHODS The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas. RESULTS The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas. CONCLUSIONS The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previously found using the microscopic technique. In cases in which the intracavernous internal carotid artery was encased (Grade 4), all the adenomas were invasive and the GTR/ER rate was 0%/0%. The authors suggest the addition of Grades 3A and 3B to distinguish the strikingly different outcomes of adenomas invading the superior CS compartments and those invading the inferior CS compartments.

OBJECT Surgery of suspected low-grade gliomas (LGGs) poses a special challenge for neurosurgeons due to their diffusely infiltrative growth and histopathological heterogeneity. Consequently, neuronavigation with multimodality imaging data, such as structural and metabolic data, fiber tracking, and 3D brain visualization, has been proposed to optimize surgery. However, currently no standardized protocol has been established for multimodality imaging data in modern glioma surgery. The aim of this study was therefore to define a specific protocol for multimodality imaging and navigation for suspected LGG. METHODS Fifty-one patients who underwent surgery for a diffusely infiltrating glioma with nonsignificant contrast enhancement on MRI and available multimodality imaging data were included. In the first 40 patients with glioma, the authors retrospectively reviewed the imaging data, including structural MRI (contrast-enhanced T1-weighted, T2-weighted, and FLAIR sequences), metabolic images derived from PET, or MR spectroscopy chemical shift imaging, fiber tracking, and 3D brain surface/vessel visualization, to define standardized image settings and specific indications for each imaging modality. The feasibility and surgical relevance of this new protocol was subsequently prospectively investigated during surgery with the assistance of an advanced electromagnetic navigation system in the remaining 11 patients. Furthermore, specific surgical outcome parameters, including the extent of resection, histological analysis of the metabolic hotspot, presence of a new postoperative neurological deficit, and intraoperative accuracy of 3D brain visualization models, were assessed in each of these patients. RESULTS After reviewing these first 40 cases of glioma, the authors defined a specific protocol with standardized image settings and specific indications that allows for optimal and simultaneous visualization of structural and metabolic data, fiber tracking, and 3D brain visualization. This new protocol was feasible and was estimated to be surgically relevant during navigation-guided surgery in all 11 patients. According to the authors' predefined surgical outcome parameters, they observed a complete resection in all resectable gliomas (n = 5) by using contour visualization with T2-weighted or FLAIR images. Additionally, tumor tissue derived from the metabolic hotspot showed the presence of malignant tissue in all WHO Grade III or IV gliomas (n = 5). Moreover, no permanent postoperative neurological deficits occurred in any of these patients, and fiber tracking and/or intraoperative monitoring were applied during surgery in the vast majority of cases (n = 10). Furthermore, the authors found a significant intraoperative topographical correlation of 3D brain surface and vessel models with gyral anatomy and superficial vessels. Finally, real-time navigation with multimodality imaging data using the advanced electromagnetic navigation system was found to be useful for precise guidance to surgical targets, such as the tumor margin or the metabolic hotspot. CONCLUSIONS In this study, the authors defined a specific protocol for multimodality imaging data in suspected LGGs, and they propose the application of this new protocol for advanced navigation-guided procedures optimally in conjunction with continuous electromagnetic instrument tracking to optimize glioma surgery.

Background: Although considered a standard neurosurgical procedure, endoscopic third ventriculostomy (ETV) is associated with a relatively high complication rate that is predominantly related to malpositioning of the trajectory., Objective: To develop an advanced navigation protocol for ETV, assess its possible benefits over commonly used ETV trajectories, and apply this protocol during surgery., Methods: After development of our advanced protocol, the imaging data of 59 patients who underwent ETV without navigation guidance was transferred to our navigation software. An individualized endoscope trajectory was created according to our protocol in all cases. This trajectory was compared with 2 standard trajectories, especially with regard to the distance to relevant neuronal structures: a trajectory manually measured on preoperative radiological images, as performed in all 59 cases, and a trajectory resulting from a commonly used fixed coronal burr hole. Subsequently, we applied the protocol in 15 ETVs to assess the feasibility and procedural complications., Results: Our individualized trajectory resulted in a significantly greater distance to the margins of the foramen of Monro, and the burr hole was located more posteriorly from the coronal suture in comparison with the standard trajectories. The advanced ETV technique was feasible in all 15 procedures, and no major complications occurred in any procedure. In 1 patient, a fornix contusion without clinical correlation was observed., Conclusion: Our data indicate that the proposed navigation protocol for ETV optimizes the distance of the endoscope to important neuronal structures. Continuous endoscope and puncture device guidance may further add to the safety of this procedure.

Background: For stereotactic implantation of depth electrodes in refractory epilepsy, both frame-based and frameless techniques have been developed. The higher versatility of current frameless techniques compared with framed-based methods is paid by the need of a standard burr hole for the implantation of 1 electrode., Objective: To develop a frameless method that allows convenient implantation of the electrode via a percutaneous bolt as used in frame-based methods, thereby avoiding the need for a standard burr hole., Methods: We adopted our technique from frameless stereotactic biopsy and designed the GIDE, a bone-fixated Guide for Implantation of Depth Electrodes. This reducing sleeve works as a stabilizer of the neuronavigation arm through bony contact and allows percutaneous stereotactic drilling, screwing of an implantation bolt, and placement of the depth electrode., Results: Twenty-six electrodes in 7 patients (5 male and 2 female patients; median age, 19.6 years; range, 5.5-39.1 years) were successfully implanted. The overall accuracy was comparable to that of frameless stereotactic biopsy with a target deviation of 3.0±1.9 mm (mean±SD). All electrodes were within or touched the targeted anatomic structure with an adequate quality of the recordings. We encountered no hemorrhage or neurological deficit related to the depth electrode., Conclusion: Our technique combines the high versatility of frameless stereotaxy with the convenient implantation and fixation of the depth electrode via a percutaneous bolt used in frame-based stereotactic methods. Thus, our technique allows fast, efficient implantation of depth electrodes for intracranial electroencephalography recordings.

Objective: To report our clinical experience with an advanced navigation protocol that provides seamless integration into the operating workflow of endoscopic transsphenoidal surgery., Patients and Methods: From 32 consecutive cases of endoscopic transsphenoidal surgery, an optimal setup of continuous electromagnetic instrument navigation was created. Additionally, our standard multimodality image navigation of T1-weighted magnetic resonance (MR) images for soft tissue, MR angiogram for vascular structures, and computed tomography (CT) for solid bone was advanced by the addition of a CT surface rendering for fine paranasal sinus structures. The anatomic structures visualized and their clinical impacts were compared between standard and advanced visualization protocol. Bone-windowed CT images served as reference. The accuracy of the navigation setup was assessed by intraoperative landmark tests. Potential tissue shift was calculated by comparing pre- and postoperative MR angiograms of 20 macroadenomas., Results: After a learning curve of 2 cases (1 ferromagnetic interference and 1 dislocation of the patient reference tracker), the advanced navigation protocol was feasible in 30 cases. Advanced multimodality imaging was able to visualize significantly finer paranasal sinus structures than multimodality image navigation without CT surface rendering, equal to bone-windowed CT images (P < 0.001, McNemar test). This was found helpful for orientation in cases of complex sphenoid sinus anatomy. The accuracy of the advanced navigation setup corresponded to standard optic navigation with skull fixation. A tissue shift of median 2 mm (range 0-9 mm) was observed in the posterior genu of the internal carotid arteries after tumor resection., Conclusions: The advanced navigation protocol permits continuous suction-tracked navigation guidance during endoscopic transsphenoidal surgery and optimal visualization of solid bone, fine paranasal sinus structures, soft-tissue and vascular structures. This may add to the safety of the procedure especially in cases of anatomical variations and in cases of recurrent adenomas with distorted anatomy., (Copyright © 2014. Published by Elsevier Inc.)

Context: PATIENTS with acromegaly frequently display disturbances of glucose and lipid metabolism, which might contribute to their increased cardiovascular risk. Because insulin resistance and increased lipolysis have been linked to ectopic lipid deposition, altered lipid accumulation in the liver and the myocardium might contribute to metabolic and cardiac complications in these patients., Objective: The aim of this study was to investigate myocardial (MYCL) and hepatic lipid content (HCL), insulin sensitivity, and cardiac function in active acromegaly and after control of GH excess through transsphenoidal surgery., Patients: Ten patients with newly diagnosed acromegaly (ACRO&#95;active) were compared with 12 healthy controls (CON), matched for age, body mass index, and gender. In seven patients GH excess was controlled, and they were compared with their active state., Methods: MYCL and HCL were assessed by (1)H-magnetic resonance spectroscopy, pericardial fat and cardiac function by (1)H-magnetic resonance imaging, and insulin sensitivity and secretion by an oral glucose tolerance test., Results: Although MYCL tended to be lower, HCL was significantly lower in ACRO&#95;active compared with CON (HCL: 1.2% ± 1.2% vs 4.3% ± 3.5% of (1)H-magnetic resonance spectroscopy signal, P < .02). Parameters of systolic function and hypertrophy were significantly increased in ACRO&#95;active compared with CON, as were insulin secretion and resistance. After the control of GH excess, HCL and MYCL remained unchanged, but pericardial fat was increased in the patients in whom GH excess was controlled (from 11.6 ± 5.5 to 14.7 ± 6.2 cm(2), P = .02)., Conclusion: Acromegaly represents a unique condition characterized by low myocardial and hepatic lipid content despite decreased insulin sensitivity, hyperinsulinemia, and hyperglycemia. Hence, ectopic lipid accumulation does not appear to contribute to cardiac morbidity, and increased lipid oxidation might counteract ectopic lipid accumulation in GH excess.

Background: Glioma is the most common and most difficult to treat brain cancer. Despite many efforts treatment, efficacy remains low. As neurosurgical removal is the standard procedure for glioma, a method, allowing for both early detection and exact determination of the location, size and extent of the tumor, could improve a patient's positive response to therapy., New Method: We propose application of susceptibility weighted molecular magnetic resonance imaging using, targeted contrast agents, based on superparamagnetic iron oxide nanoparticles, for imaging of the, glioma rim, namely brain-tumor interface. Iron oxide attached to the targeted cells increases, susceptibility differences at the boundary between tumor and normal tissue, providing the opportunity, to utilize susceptibility weighted imaging for improved tumor delineation. We investigated potential, enhancement of the tumor-brain contrast, including tumor core and rim when using susceptibility, weighted MRI for molecular imaging of glioma., Results: There were significant differences in contrast-to-noise ratio before, 12 and 120min after contrast, agent injection between standard gradient echo pulse sequence and susceptibility weighted molecular, magnetic resonance imaging for the core-brain, tumor rim-core and tumor rim-brain areas., Comparison With Existing Methods: Currently, the most common MRI contrast agent used for glioma diagnosis is a non-specific, gadolinium-based agent providing T1-weighted enhancement. Susceptibility-weighted magnetic, resonance imaging is much less efficient when no targeted superparamagnetic contrast agents are, used., Conclusion: The improved determination of glioma extent provided by SWI offers an important new tool for, diagnosis and surgical planning., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Pulsed arterial spin-labeling is a noninvasive MR imaging perfusion method performed with the use of water in the arterial blood as an endogenous contrast agent. The purpose of this study was to determine the inversion time with the largest difference in normalized intratumoral signal intensity between high-grade and low-grade astrocytomas., Materials and Methods: Thirty-three patients with gliomas, histologically classified as low-grade (n = 7) or high-grade astrocytomas (n = 26) according to the World Health Organization brain tumor classification, were included. A 3T MR scanner was used to perform pulsed arterial spin-labeling measurements at 8 different inversion times (370 ms, 614 ms, 864 ms, 1114 ms, 1364 ms, 1614 ms, 1864 ms, and 2114 ms). Normalized intratumoral signal intensity was calculated, which was defined by the signal intensity ratio of the tumor and the contralateral normal brain tissue for all fixed inversion times. A 3-way mixed ANOVA was used to reveal potential differences in the normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas., Results: The difference in normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas obtained the most statistically significant results at 370 ms (P = .003, other P values ranged from .012-.955)., Conclusions: The inversion time by which to differentiate high-grade and low-grade astrocytomas by use of normalized vascular intratumoral signal intensity was 370 ms in our study. The normalized vascular intratumoral signal intensity values at this inversion time mainly reflect the labeled intra-arterial blood bolus and therefore could be referred to as normalized vascular intratumoral signal intensity. Our data indicate that the use of normalized vascular intratumoral signal intensity values allows differentiation between low-grade and high-grade astrocytomas and thus may serve as a new, noninvasive marker for astrocytoma grading.

Object: Subtotal resection (STR) of spinal tumors can result in tumor recurrence. Currently, no clinically reliable marker is available for intraoperative visualization of spinal tumor tissue. Protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) is capable of visualizing malignant gliomas. Fluorescence-guided resections of malignant cerebral gliomas using 5-ALA have resulted in an increased rate of complete tumor removal. Recently, the application of 5-ALA has also been described in the first cases of spinal tumors. Therefore, the aim of this observational study was to systematically investigate 5-ALA-induced fluorescence characteristics in different spinal tumor entities., Methods: Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of PpIX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification., Results: Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy., Conclusions: In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci.

Background: Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria., Methods: We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status., Results: A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%., Conclusions: Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Object: It has been over a decade since the introduction of the da Vinci Surgical System into surgery. Since then, technology has been advancing at an exponential rate, and newer surgical robots are becoming increasingly sophisticated, which could greatly impact the performance of surgery. NeuroArm is one such robotic system., Methods: Clinical integration of neuroArm, an MR-compatible image-guided robot, into surgical procedure has been developed over a prospective series of 35 cases with varying pathology., Results: Only 1 adverse event was encountered in the first 35 neuroArm cases, with no patient injury. The adverse event was uncontrolled motion of the left neuroArm manipulator, which was corrected through a rigorous safety review procedure. Surgeons used a graded approach to introducing neuroArm into surgery, with routine dissection of the tumor-brain interface occurring over the last 15 cases. The use of neuroArm for routine dissection shows that robotic technology can be successfully integrated into microsurgery. Karnofsky performance status scores were significantly improved postoperatively and at 12-week follow-up., Conclusions: Surgical robots have the potential to improve surgical precision and accuracy through motion scaling and tremor filters, although human surgeons currently possess superior speed and dexterity. Additionally, neuroArm's workstation has positive implications for technology management and surgical education. NeuroArm is a step toward a future in which a variety of machines are merged with medicine.

Intraoperative imaging disrupts the rhythm of surgery despite providing an excellent opportunity for surgical monitoring and assessment. To allow surgery within real-time images, neuroArm, a teleoperated surgical robotic system, was conceptualized. The objective was to design and manufacture a magnetic resonance-compatible robot with a human-machine interface that could reproduce some of the sight, sound, and touch of surgery at a remote workstation. University of Calgary researchers worked with MacDonald, Dettwiler and Associates engineers to produce a requirements document, preliminary design review, and critical design review, followed by the manufacture, preclinical testing, and clinical integration of neuroArm. During the preliminary design review, the scope of the neuroArm project changed to performing microsurgery outside the magnet and stereotaxy inside the bore. neuroArm was successfully manufactured and installed in an intraoperative magnetic resonance imaging operating room. neuroArm was clinically integrated into 35 cases in a graded fashion. As a result of this experience, neuroArm II is in development, and advances in technology will allow microsurgery within the bore of the magnet. neuroArm represents a successful interdisciplinary collaboration. It has positive implications for the future of robotic technology in neurosurgery in that the precision and accuracy of robots will continue to augment human capability.

Virtual endoscopy is the computerized creation of images depicting the inside of patient anatomy reconstructed in a virtual reality environment. It permits interactive, noninvasive, 3-dimensional visual inspection of anatomical cavities or vessels. This can aid in diagnostics, potentially replacing an actual endoscopic procedure, and help in the preparation of a surgical intervention by bridging the gap between plain 2-dimensional radiologic images and the 3-dimensional depiction of anatomy during actual endoscopy. If not only the endoscopic vision but also endoscopic handling, including realistic haptic feedback, is simulated, virtual endoscopy can be an effective training tool for novice surgeons. In neurosurgery, the main fields of the application of virtual endoscopy are third ventriculostomy, endonasal surgery, and the evaluation of pathologies in cerebral blood vessels. Progress in this very active field of research is achieved through cooperation between the technical and the medical communities. While the technology advances and new methods for modeling, reconstruction, and simulation are being developed, clinicians evaluate existing simulators, steer the development of new ones, and explore new fields of application. This review introduces some of the most interesting virtual reality systems for endoscopic neurosurgery developed in recent years and presents clinical studies conducted either on areas of application or specific systems. In addition, benefits and limitations of single products and simulated neuroendoscopy in general are pointed out.

Background: Cranial surgical navigation is most commonly performed by registration with fiducial markers, optic tracking, and intermittent pointer-based application., Objective: To assess the accuracy and applicability of an advanced cranial navigation setup., Methods: Continuous electromagnetic instrument navigation was used in 136 neurosurgical cases with a standard navigation system. A phantom head in an intraoperative magnetic resonance imaging environment was used to compare the accuracy of the advanced and standard navigation setups., Results: A navigated suction device was used in 71 cases of intracranial tumor surgery and 46 cases of endoscopic transsphenoidal surgery. The ventriculoscope was navigated in 6 cases and the stereotactic biopsy needle in 4 cases. Electromagnetic tracking was used for catheter placement in 9 cases. The learning curve comprised 6 of the 136 cases during the first month of application. No significant difference was observed at the intracranial target points between the standard navigation setup using optic tracking, fiducial marker registration, and pointer and the advanced navigation setup with electromagnetic tracking, surface-based registration, and navigation of a field-detecting stylet in a standard metal suction tube when performed outside the 5-G line of the 3.0-T intraoperative magnetic resonance imaging., Conclusion: Continuous instrument navigation is the prerequisite for seamless integration of navigation systems into the neurosurgical operating workflow. Our data confirm that the application of preoperative imaging, surface-merge registration, and continuous electromagnetic tip-tracked instrument navigation may provide such integration without a significant reduction in accuracy compared with standard navigation.

Background: Precise lesion localization is necessary for neurosurgical procedures not only during the operative approach, but also during the preoperative planning phase., Objective: To evaluate the advantages of 3-dimensional (3-D) brain surface visualization over conventional 2-dimensional (2-D) magnetic resonance images for surgical planning and intraoperative guidance in brain tumor surgery., Methods: Preoperative 3-D brain surface visualization was performed with neurosurgical planning software in 77 cases (58 gliomas, 7 cavernomas, 6 meningiomas, and 6 metastasis). Direct intraoperative navigation on the 3-D brain surface was additionally performed in the last 20 cases with a neurosurgical navigation system. For brain surface reconstruction, patient-specific anatomy was obtained from MR imaging and brain volume was extracted with skull stripping or watershed algorithms, respectively. Three-dimensional visualization was performed by direct volume rendering in both systems. To assess the value of 3-D brain surface visualization for topographic lesion localization, a multiple-choice test was developed. To assess accuracy and reliability of 3-D brain surface visualization for intraoperative orientation, we topographically correlated superficial vessels and gyral anatomy on 3-D brain models with intraoperative images., Results: The rate of correct lesion localization with 3-D was significantly higher (P = .001, χ), while being significantly less time consuming (P < .001, χ) compared with 2-D images. Intraoperatively, visual correlation was found between the 3-D images, superficial vessels, and gyral anatomy., Conclusion: The proposed method of 3-D brain surface visualization is fast, clinically reliable for preoperative anatomic lesion localization and patient-specific planning, and, together with navigation, improves intraoperative orientation in brain tumor surgery and is relatively independent of brain shift.

Stereotactic biopsies represent a routine neurosurgical procedure for the diagnosis of intracranial lymphomas and selected diffusely infiltrating gliomas. Acquisition of tissue samples that do not allow correct tumor typing and grading is, however, not uncommon. Five-aminolevulinic acid (5-ALA) has been shown to accumulate in malignant tumor tissue. The aim of this study was to prospectively investigate the clinical usability of 5-ALA for intraoperative detection of representative tissue in stereotactic tumor biopsies. Fifty consecutive patients underwent frameless stereotactic biopsy for a suspected brain tumor. 5-ALA was administered 4 h before anesthesia. Serial biopsy samples were obtained and intraoperatively checked for 5-ALA fluorescence (strong, vague, or none) using a modified neurosurgical microscope. All samples were examined for the presence of representative tumor tissue according to neuroimaging (MRI, positron emission tomography, and/or chemical shift imaging) and histopathological parameters. Visible 5-ALA fluorescence was observed in 43/50 patients (strong in 39 and vague fluorescence in four cases). At biopsy target, 52/53 samples of glioblastomas, 9/10 samples of gliomas grade III, and 14/16 samples of lymphomas revealed strong 5-ALA fluorescence. Samples with strong 5-ALA fluorescence were only observed at, but not outside the biopsy target. All tissue samples with strong 5-ALA fluorescence were representative according to our neuroimaging and histopathological criteria (positive predictive value of 100%). Our data indicate that strong 5-ALA fluorescence is a reliable and immediately available intraoperative marker of representative tumor tissue of malignant gliomas and intracranial lymphomas in stereotactic biopsies. Thereby, the application of 5-ALA in stereotactic brain tumor biopsies may in future reduce costs for operating room and neuropathology and may decrease procedure-related morbidity.

Detailed knowledge of the vascular anatomy of the anterior skull base is critical to successful surgery in this area. Whereas conventional neuronavigational approaches combine MRI (+/- contrast) for tumor visualization and CT (+/- C) for bony and vascular anatomy, we describe the Canadian and Austrian experiences using a novel protocol integrating MR angiography (MRA) into surgical neuronavigation to provide superior visualization of the carotid arteries. The pre-operative imaging protocol employs a T1-weighted, 3D fast spoiled gradient echo MRI (+/- C) for soft tissue anatomy, a plain CT for bony anatomy, and a 3D time-of-flight MR angiography for carotid anatomy. The series are imported into the Medtronic StealthStation((R)) TREON((R)) Treatment Guidance System; during intra-operative neuronavigation, each series (MRI, CT, MRA) can be viewed individually, or layered and viewed as a composite image. Our protocol has important advantages. First, it provides detailed tissue, tumor, vascular and bony anatomy. Second, a contrast CT is not necessary; this is important, as numerous reports have highlighted the nephrotoxic nature of radiographic contrast material. Third, visualization of the carotid system is superior than can be obtained from CT angiography. We use this unique imaging protocol routinely for our endoscopic transsphenoidal surgeries to provide superior visualization of the carotid arteries during anterior skull base surgery.

Background: Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling., Methods: 5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum (11)C-methionine positron emission tomography uptake (PET(max)) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI)., Results: Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PET(max) in all patients. MIB-1 LI was significantly higher in 5-ALA-positive than in nonfluorescent areas within a given tumor., Conclusions: The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments.

Purpose: Virtual endoscopy has already proven its benefit for pre-operative planning of endoscopic pituitary surgery. The translation of such a system into the operating room is a logical consequence, but only a few general intra-operative image guided systems providing virtual endoscopic images have been proposed so far. A discussion of related visualization and interaction problems occurring during sinus and pituitary surgery is still missing., Methods: This paper aims at filling this gap and proposes a system that integrates an existing virtual endoscopy system originally designed for pre-operative planning of pituitary surgery with a professional intra-operative navigation system. Visualization and interaction possibilities of the pre-operative planning system have been extended to fulfill the special requirements to the system if used for intra-operative navigation of endonasal transsphenoidal pituitary surgery., Results: The feasibility of the system has been successfully tested on 1 cadaver and 12 patients. The virtual endoscopic images were found useful (1) during the endonasal transsphenoidal approach in cases of anatomic variations and for the individually tailored opening of the sellar floor, and (2) during tumor resection for respecting the internal carotid artery. The visualization of hidden anatomical structures behind the bony walls of the sphenoid sinus during the sellar phase of the surgery has been found most beneficial., Discussion: According to our data, intra-operative virtual endoscopy provides additional anatomical information to the surgeon. By depicting individual anatomical variations in advance, it may add to the safety of this frequent neurosurgical procedure.

Object: In residual nonfunctioning pituitary adenomas, reliable prognostic parameters indicating probability of tumor progression are needed. The Ki 67 expression/MIB-1 labeling index (LI) is considered to be a promising candidate factor. The aim in the present study was to analyze the clinical usefulness of MIB-1 LI for prognosis of tumor progression., Methods: The authors studied a cohort of 92 patients with nonfunctioning pituitary adenomas. Based on sequential postoperative MR images, patients were classified as tumor free (51 patients) or as harboring residual tumor (41 individuals). The residual tumor group was further subdivided in groups with stable residual tumors (14 patients) or progressive residual tumors (27 patients). The MIB-1 LI was assessed in tumor specimens obtained in all patients, and statistical comparisons of MIB-1 LI of the various subgroups were performed., Results: The authors found no significant difference of MIB-1 LI in the residual tumor group compared with the tumor-free group. However, MIB-1 LI was significantly higher in the progressive residual tumor group, compared with the stable residual tumor group. Additionally, the time period to second surgery was significantly shorter in residual adenomas showing an MIB-1 LI>3%., Conclusions: The data indicate that MIB-1 LI in nonfunctioning pituitary adenomas is a clinically useful prognostic parameter indicating probability of progression of postoperative tumor remnants. The MIB-1 LI may be helpful in decisions of postoperative disease management (for example, frequency of radiographic intervals, planning for reoperation, radiotherapy, and/or radiosurgery).

Objective: Virtual endoscopy (vE) is the navigation of a camera through a virtual anatomical space that is computationally reconstructed from radiological image data. Inside this three-dimensional space, arbitrary movements and adaptations of viewing parameters are possible. Thereby, vE can be used for noninvasive diagnostic purposes and for simulation of surgical tasks. This article describes the development of an advanced system of vE for endoscopic transsphenoidal pituitary surgery and its application to teaching, training, and in the routine clinical setting., Methods: The vE system was applied to a series of 35 patients with pituitary pathology (32 adenomas, three Rathke's cleft cysts) operated endoscopically via the transsphenoidal route at the Department of Neurosurgery of the Medical University Vienna between 2004 and 2006., Results: The virtual endoscopic images correlated well with the intraoperative view. For the transsphenoidal approach, vE improved intraoperative orientation by depicting anatomical landmarks and variations. For planning a safe and tailored opening of the sellar floor, transparent visualization of the pituitary adenoma and the normal gland in relation to the internal carotid arteries was useful., Conclusion: According to our experience, vE can be a valuable tool for endoscopic transsphenoidal pituitary surgery for training purposes and preoperative planning. For the novice, it can act as a simulator for endoscopic anatomy and for training surgical tasks. For the experienced pituitary surgeon, vE can depict the individual patient's anatomy, and may, therefore, improve intraoperative orientation. By prospectively visualizing unpredictable anatomical variations, vE may increase the safety of this surgical procedure.

Objective: Surgical resection of cranial base meningiomas is often limited owing to involvement of crucial neural structures. Within the last 2 decades Gamma Knife radiosurgery (GKRS) has gained increasing importance as an adjunct treatment after incomplete resection and as an alternative treatment to open surgery. However, reports of long-term results are still sparse. We therefore performed this study to analyze the long-term results of GKRS treatment of cranial base meningiomas, following our previously published early follow-up experience., Methods: A retrospective analysis of the medical files for Gamma Knife and surgical treatments, clinicoradiological findings, and outcome was carried out focusing on tumor control, clinical course, and morbidity., Results: Between 1992 and 1995, we treated 36 patients with cranial base meningiomas using GKRS (male:female ratio, 1:5; mean age, 59 yr; range, 44-89 yr). Twenty-five patients were treated with GKRS after open surgery, and 11 patients received GKRS alone. Tumor control, neurological outcomes, and adverse effects were analyzed after a long-term follow-up period (mean, 103 mo; range, 70-133 mo) and compared with our previous results after an early follow-up period (mean, 48 mo; range, 36-76 mo). Control of tumor growth was achieved in 94% of patients. Compared with the early follow-up period, the late neuroradiological effects of GKRS on cranial base meningiomas were continuing tumor shrinkage in 11 patients (33%), stable tumor size in 20 patients (64%) and tumor progression in two meningiomas (6%). The neurological status improved in 16 patients (44%), remained stable in 19 patients (52%), and deteriorated in one patient (4%). Adverse side effects of GKRS were found only during the early follow-up period., Conclusion: Our data confirm that GKRS is not only a safe and effective treatment modality for cranial base meningiomas in short-term observation, but also in a mean long-term follow-up period of more than 8 years. Tumor shrinkage and clinical improvement also continued during the longer follow-up period.

Survivin expression has been described as prognostic factor in various tumor types and has been shown to correlate with cytologic anaplasia in ependymoma. We immunohistochemically studied survivin expression and its association with Ki-67 and topoisomerase IIalpha (TIIalpha) expression and outcome in 63 patients with intracranial ependymoma. Survivin is expressed in a fraction of nuclei of tumor and endothelial cells including mitotic figures. Survivin indices range from 0.6% to 43.2% and correlate with Ki-67 and TIIalpha indices. On average, 62.86% of Ki-67-expressing tumor cell nuclei coexpress survivin, whereas 92.2% of survivin-expressing nuclei coexpress Ki-67. High survivin, Ki-67, and TIIalpha indices univariately correlated with an unfavorable outcome. In multivariate analysis, only the Ki-67 index remained an independent prognostic factor. In ependymoma, survivin is expressed in a subset of proliferating cells. High survivin expression is associated with poor patient outcome. However, the Ki-67 index is a more accurate prognostic marker than the survivin or TIIalpha index.

We investigated angiogenic patterns and expression of hypoxia-related tissue factors and their prognostic impact in 100 cases of intracranial ependymoma. Angiogenic patterns were evaluated by anti-CD34 immunolabeling. Hypoxia-related factors carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1 alpha (HIF-1alpha) were visualized by immunohistochemistry, and vascular endothelial growth factor (VEGF) mRNA by in situ hybridization. Expression patterns of VEGF and CA9 are similar with regard to distribution (perinecrotic) and extent. HIF-1alpha expression occurs in a significantly smaller fraction of cases and only in a few tumor cells without clear association with necrosis. Expression of VEGF and CA9, but not HIF-1alpha, is associated with a bizarre angiogenic subtype. Combined expression of two or three hypoxia markers (high hypoxia score) associates with presence of necrosis, high proliferation index, bizarre vascular pattern, and increased cellularity. Univariate analysis indicated that patients with high hypoxia score had significantly shorter survival. On multivariate analysis, only proliferation index and extent of resection remained independent predictive factors. We conclude that bizarre vascular pattern, necrosis and high hypoxia score are frequently detectable in intracranial ependymoma, but seem less important for patient outcome than tumor cell proliferation.

For recurrent and untreatable meningiomas alternative therapies, such as anti-progesterone treatment, have been sought. However, the few clinical studies have not determined progesterone receptor (PgR) expression in most cases, and studies correlating quantitative PgR expression (PgR index) with clinico-pathological variables are scarce. The aim of our study was to assess the PgR indices in a consecutive series of meningiomas and correlate these values with clinico-pathological parameters. We analyzed immunohistochemically 82 consecutive meningioma specimens (73 primary and nine recurrent tumors) for PgR and Ki-67 antigen (MIB-1). The male/female ratio was 1:1.7, and median age at the time of surgery was 57 years (range 29-77 years). The series comprised 55 grade I (subtyped as 36 meningothelial, seven fibrous, nine transitional, two psammomatous, and one angiomatous), 23 grade II, and one grade III meningiomas. Nuclear immunostaining for PgR was positive in 56 meningioma specimens (71%). PgR index was 21.4+/-2.8% (mean +/- SE; range 0-79%). Significantly higher expression was found in male patients in the age group <50 years than in those > or = 60 years and in grade I meningothelial meningiomas than in fibrous and transitional subtypes. There was a trend to lower PgR indices in non-benign meningiomas. Cell proliferation rate (MIB-1 index) was 4.4 +/- 0.4% (mean +/- SE; range 0.3-15.4%). Significantly higher MIB-1 indices were found in male than female patients,in recurrent than primary and in grade II than grade I meningiomas. We observed a trend to higher PgR indices in meningiomas with MIB-1 index <5%. In sum, the highest PgR index in our series was observed in patients under the age of 50 years with WHO grade I meningiomas of the meningothelial subtype and low cell proliferation indices. If hormonal therapy has a direct action on the PgR, these patients should respond best to anti-progesterone treatment. We conclude that PgR index is variable in meningioma, depending on clinical parameters and histopathological features. Stratification of anti-progesterone therapy trials on the basis of PgR index should be considered., (Copyright 2004 Springer-Verlag)

Virtual endoscopy (vE) allows simulated three-dimensional (3-D) visualisation of anatomical structures by computerised reconstruction of radiological images. The aim of this study was to evaluate the feasibility of vE and its potential benefits for endoscopic transsphenoidal pituitary surgery. vE was realised using a commercially available ray-casting software plugin of a picture archiving and communications system (PACS). For this study, the vE system was enhanced with volume segmentation, transparency and cutting tools. The data for vE were derived from high resolution computed tomography (CT) scans of 22 patients with pituitary pathology (20 pituitary adenomas, 2 Rathke's cleft cysts) preoperatively. Anatomic structures were identified on vE images and compared with the intraoperative endoscopic views. The simulated 3-D vE images were found to be comparable to the intraoperative endoscopic anatomy in terms of distortion and angle of view. vE was found to be particularly useful for the preoperative depiction of 1) the nasal anatomy and its variations for choosing the side of the approach, 2) the sphenoid sinus septae and chambers for improved intraoperative orientation, 3) the transparent 3-D simulated visualisation of the pituitary gland, tumour and adjacent anatomic structures in relation to the sphenoid sinus landmarks for planning the opening of the sellar floor. We conclude that vE harbours the potential to become a valuable tool in endoscopic pituitary surgery for training purposes and preoperative planning. Furthermore, vE may add to the safety of interventions in case of anatomic variations.

Histopathologic grading of ependymomas is considered unreliable in terms of outcome prediction. Quantification of tumor cell proliferation may be useful for outcome prediction. We analyzed prognostic and predictive values of tumor cell proliferation rates using anti-Ki-67 antigen (MIB-1 antibody) and anti-topoisomerase-IIalpha (Topo-IIalpha) immunolabeling on tumor samples of 103 consecutive ependymoma patients 0.1 to 74.4 years of age. In this patient cohort, the following clinical and histopathologic parameters showed significant correlation with overall survival on univariate analysis: extent of resection, use of an operating microscope, radiologic imaging with computed tomography and/or magnetic resonance imaging, radiotherapy, tumor size (cutoff 3 cm), WHO grade, presence of tumor necrosis, increased cellularity, microvascular proliferation, and low/high Ki-67 and Topo-IIalpha indices (cutoff 20.5% and 9.4%, respectively). On multivariate analysis, incomplete resection and high Ki-67 index remained independent factors of adverse patient outcome. In Kaplan-Meier survival analysis, low (<20.5%) or high (> or = 20.5%) Ki-67 indices predicted favorable (> or = 5 years) or unfavorable (<5 years) patient outcome at 79% and 70%, respectively. We conclude that Ki-67 immunolabeling index is an independent prognostic factor and accurate predictor of outcome in patients with intracranial ependymoma. Thus, assessment of Ki-67 index in intracranial ependymoma is useful for outcome prediction in the routine diagnostic setting.

Functional imaging of brain tumors assists biopsy localization, therapy monitoring, and differentiating tumor recurrence from radiation necrosis. Tumor vascularization is a strong prognostic predictor in solid tumors and also a key factor of tracer uptake. However, the relationship of brain tumor vascularization and functional imaging has not yet been investigated sufficiently so far. In the present study, we correlated histologically assessed microvessel density as an objective parameter for brain tumor vascularization with imaging data. Four male patients were studied. After 99mTc-MIBI scintigraphy, all patients had a MRI within 2 weeks. Histology showed microcystic astrocytoma, glioblastoma (n = 2), and anaplastic oligodendroglioma, respectively. Microvessel density was lowest in the microcystic astrocytoma, medium in the glioblastomas, and highest in the anaplastic oligodendroglioma. Scintigraphy visualized only the glioblastomas, but not the microcystic astrocytoma or oligodendroglioma. Our data showed no correlation between tumor microvessel density and 99mTc-MIBI scintigraphy. Thus, we conclude that scintigraphic visualization of brain tumors is not strictly dependent on tumor vascularization.

Postoperative epidural haematoma distant to a site of craniotomy is a rare but possibly hazardous complication. We report a 31-year-old female who presented with a history of chronic hydrocephalus due to fourth-ventricular plexus papilloma. Following resection of the posterior fossa tumour with intraoperative placement of a ventricular drainage, she consecutively developed four supratentorial epidural haematomas at different locations, all necessitating evacuation. The clinical manifestations ranged from subtle neurological deficits to signs of tentorial herniation; the ultimate outcome was complete recovery. Rapid tapering of CSF pressure after long-standing hydrocephalus and clotting disorders could be implicated as causative factors. We stress the importance of early postoperative CT scan and optimal management of ventricular pressure and coagulation status to detect and prevent this possibly life-threatening complication.

Object: The aim of this study was to determine the value of high-field magnetic resonance (MR) imaging for diagnosis and surgery of sellar lesions., Methods: High-field MR images were obtained using a 3-tesla unit with emphasis on sellar and parasellar structures in 21 patients preoperatively to delineate endo-, supra-, and parasellar anatomical structures. Special attention was given to the medial border of the cavernous sinus and possible invasion of a sellar tumor therein, and to assessing the application of high-resolution images during intraoperative neuronavigation. The 3-tesla MR images were compared with the standard MR images already obtained and with intraoperative findings. Anatomical structures were studied in all 42 cavernous sinuses; in 32 of them comparisons with intraoperative findings were possible. The medial cavernous sinus border was rated intact in 53% on standard MR images, in 72% on 3-tesla MR images, and in 81% intraoperatively. With a positive correlation to surgical findings on 84% of 3-tesla MR images compared with 59% of standard MR images, a sensitivity of 83% compared with 67%, and a specificity of 84% compared with 58% (p = 0.016, McNemar test), 3-tesla MR imaging was superior for predicting tumor invasion through the medial cavernous sinus border. Although no difference was noted in delineation of the medial, superior, and inferior compartments, there was a better delineation of the lateral cavernous sinus compartment with 3-tesla MR imaging. This compartment was clearly visible on 40 sides (95%) on 3-tesla MR images compared with 34 sides (81%) on standard MR images. Identification of the cavernous sinus segments of the third, fourth, fifth (V1 and V2), and sixth cranial nerves was improved using high-resolution 3-tesla imaging compared with standard MR imaging. A mean of four cranial nerves was found as hypointense spots (range two-five spots) on 3-tesla MR imaging compared with a mean of three (range zero-four spots) on standard MR imaging. After addition of contrast agents, the anterior pituitary gland was found to be highly intense on 78% of T1-weighted three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) 3-tesla MR images compared with 73% of standard T1-weighted MR images. The optochiasmatic system displayed increased intensity on pre-contrast T1-weighted MPRAGE 3-tesla compared with standard T1-weighted MR images; it was hyperintense on 76% of 3-tesla compared with 15% of standard MR images, which was helpful for its delineation from suprasellar pituitary and tumor structures. Intraoperative navigation guided by fusion of 3-tesla MR images and computerized tomography (CT) scans was performed in seven patients. Whereas CT scanning was used during the transsphenoidal approach to depict the nasal bone structures, 3-tesla MR imaging was particularly useful for the visualization of parasellar tumor extension during microsurgical and/or endoscopic resection., Conclusions: Due to its higher resolution, 3-tesla MR imaging was found to be superior to standard MR imaging for the delineation of parasellar anatomy and tumor infiltration of the cavernous sinus, and this modality provided improved imaging for intraoperative navigation.

Tumor-to-brain contrast after gadolinium administration using MP-RAGE and T1-SE scans in patients with primary and secondary brain tumors was significantly higher at 3 T than at 1.5 T. The subjective assessment of cumulative triple-dose 3 Tesla images obtained the best results in the detection of brain metastases compared with other sequences followed by 1.5 T cumulative triple-dose enhanced images. In macroadenomas of the hypophysis, contrast-enhanced 3 T MRI was superior to standard MRI in the diagnosis of cavernous sinus infiltration and in visualization of cranial nerves within the cavernous sinus. Due to higher spatial resolution, contrast-enhanced MR venography at 3 T showed more details in and around tumors than at 1.5 T, additionally enhanced by stronger susceptibility weighting and higher signal-to-noise ratio at 3 T. In summary, administration of gadolinium-based contrast agent produces higher contrast between tumor and normal brain at 3 T than at 1.5 T, helps to detect more cerebral metastases at 3 T versus 1.5 T in single and cumulative triple dose, improves the evaluation of macroadenomas of the hypophysis, and makes MR venography at 3 T clinically attractive with increase in spatial resolution within the same measurement time, thus providing more detailed information.

Objective: To analyze the effect of prone position on cerebral perfusion pressure and brain tissue oxygen partial pressure in subarachnoid hemorrhage patients with acute respiratory distress syndrome (ARDS)., Design: Clinical study with retrospective data analysis., Setting: Neurosurgical intensive care unit of a primary level university hospital., Patients: Sixteen patients treated for intracranial aneurysm rupture with initial Hunt and Hess grade III or worse who developed ARDS within 2 wks after the bleeding., Interventions: Routine neurosurgical intensive care treatment for subarachnoid hemorrhage and posthemorrhagic vasospasm including cerebral monitoring with continuous intracranial pressure and brain tissue oxygen partial pressure recordings., Measurements and Main Results: Hemodynamics, arterial oxygenation, ventilatory setting, intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen partial pressure in the supine as well as in the prone position were analyzed and compared. A significant increase in Pao(2) from 97.3 +/- 20.7 torr (mean +/- sd) in the supine position to 126.6 +/- 31.7 torr in the prone position was joined by a significant increase in brain tissue oxygen partial pressure from 26.8 +/- 10.9 torr to 31.6 +/- 12.2 torr (both p <.0001), whereas intracranial pressure increased from 9.3 +/- 5.2 mm Hg to 14.8 +/- 6.7 mm Hg and cerebral perfusion pressure decreased from 73.0 +/- 10.5 mm Hg to 67.7 +/- 10.7 mm Hg (both p <.0001)., Conclusions: The beneficial effect of prone positioning on cerebral tissue oxygenation by increasing arterial oxygenation appears to outweigh the expected adverse effect of prone positioning on cerebral tissue oxygenation by decreasing cerebral perfusion pressure in ARDS patients.

Macrotumors of the sella region usually involve the suprasellar and less commonly the parasellar space. The suprasellar extension of pituitary adenoma, meningeoma, craniopharyngioma, and hypothalamic or chiasmatic glioma count for the most frequent neoplastic entities. In macroadenomas of the pituitary gland invasion of parasellar spaces may occur in 6-10%. Imaging techniques are directed to increase the likelihood of surgical cure and to detect aggressive tumour invasion into surrounding tissues. A dedicated classification basing on indirect MRI signs of tumour extension has been established. With high-resolution high-field (3T) MRI the sella region may be displayed to provide better information compared to lower field strengths.

Due to their diversity, pituitary adenomas represent an interdisciplinary therapeutic challenge in regard to endocrinology, radiology and neurosurgery. Advanced radiological methods such as magnetic resonance imaging (MRI) and the possibility of three-dimensional reconstruction have profoundly improved surgical planning and intraoperative neuronavigation. With the application of modern surgical techniques like endoscope-assisted microsurgery or pure endoscopic surgery further improvements in the treatment of pituitary adenomas at difficult locations can be expected. Major prognostic factors predicting surgical outcome are extension of the adenoma and invasivity into adjacent structures. Both may be perfectly visualized by high-resolution MRI. The proliferation marker MIB-1 as a parameter of growth-rate and invasivity of pituitary adenomas provides information for postoperative management in terms of additional treatment and follow-up imaging. The current management of pituitary adenomas is discussed according to the different therapeutic options available and new developments are presented.

Objective: Frameless stereotactic navigation devices require preoperative application of skin markers (SM) and planning radiography, which limits their even wider use. Therefore, we prospectively studied the applicability and accuracy of anatomic "natural" markers (NM) for image registration., Methods: The accuracy of NM was evaluated in 26 patients operated on in the supine (n=24) or sitting (n=2) position, either by comparison to our standard navigation protocol using SM and planning radiography or by the deviation of anatomic landmarks using a routine diagnostic radiograph. In 21 cases, NM were compared to SM with planning radiography (computed tomography, or CT, in nine cases and magnetic resonance imaging, or MRI, in 12). The root mean square error (RMSE) of the registered volume was calculated by the Philips EasyGuide Neuro frameless stereotactic navigation system and compared between the two registration modalities., Results: The mean RMSE was 3.2 mm+/-1.0 mm standard deviation using NM vs 2.9+/-1.0 mm using self-adhesive SM (P=0.13, Student's t-test). Computed tomography was slightly more accurate than MRI planning (mean RMSE 3.2 mm vs 3.3 mm). In three cases, diagnostic radiography (MRI) was used with a mean RMSE of 5.3 mm but acceptable intraoperative landmark correlation., Conclusion: Our pilot study demonstrates insignificant loss of registration accuracy using NM compared to SM. Additionally, the radiologic planning investigation and accuracy loss due to SM movement may be avoided.

Stereotactic radiosurgery (RS) and surgery have proved to be effective treatment modalities for brain metastasis. We followed 133 patients whose treatment for intracranial disease was either RS or a single surgical resection at the University of Vienna from August 1992 through October 1996. All patients who received additional Whole Brain Radiotherapy were included. This was a retrospective, case-control study comparing these treatment modalities. Sixty-seven patients were treated by RS and 66 patients were treated by microsurgery. The median size of the treated lesions for RS patients was 7800 mm3, and 12500 mm3 for microsurgery patients, respectively. The median dose delivered to the tumour margin for RS patients was 17 gray. The median survival for patients after RS was 12 months, and 9 months for patients after microsurgery. This difference was not statistically significant (p = 0.19). Comparison of local tumour control, defined as absence of regrowth of a treated lesion, showed that tumours following RS had a preferred local control rate (p < 0.05). Univariate and multivariate analysis showed that this fact was due to a greater response rate of "radioresistant" metastasis to RS (p < 0.005). Postradiosurgical complications included the onset of peritumoural oedema (n = 5) and radiation necrosis (n = 1). Two patients after microsurgery experienced local wound infection. One postoperative death occurred due to pulmonary embolism in this group. On the basis of our data we conclude that RS and microsurgery combined with Whole Brain Radiotherapy are comparable modalities in treating single brain metastasis. Concerning morbidity and local tumour control, in particular in cases of "radioresistant" primary tumours, RS is superior. Therefore we advocate RS except for cases of large tumours (> 3 cm in maximum diameter) and for those with mass effect.