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Objective We sought to analyze long-term outcome and quality of life after surgery of cerebral cavernomas (CCs) with special regard to localization (brainstem vs. nonbrainstem). Methods We conducted a retrospective study in a tertiary care center (2000–2010). Clinical charts were analyzed. Health-related quality of life (QoL) was evaluated with the Short Form−36 questionnaire. Results The study included 60 patients (21 male, 39 female, mean age 39.8 years). The distribution was 67% supratentorial, 7% cerebellar, and 26% brainstem (BS). In the BS group, 87.5% had a preoperative deficit versus 18.2% in the nonbrainstem group (NBS). Operative neurologic morbidity was 31.3% for BS versus 11.4% for NBS. After mean follow-up of 43 months, neurologic status was better or the same as compared with the preoperative status in 75% of BS and all of NBS. SF-36 showed no significant differences between all cavernoma patients compared with a normative healthy population except for a better "pain" score. Subgroup analysis found the same results when comparing NBS with the normative population. Comparison of BS versus norm and NBS, respectively, showed worse scores for BS in physical but not mental health ( P ≤ 0.01). Conclusion Clinical outcome was different depending on location: NBS recovered the same neurologic status as preoperatively and showed better QoL in physical health and lower working inability than BS. Surprisingly, there was no difference in mental health. Moreover, QoL of the operated cavernoma population after long-term follow-up did not differ from the norm. We conclude that surgery of cavernomas even in eloquent areas may result in favorable outcome and high patient satisfaction.

The study was performed to preoperatively assess the cartilage integrity of cervical intervertebral discs (IVDs) using Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC). Therefore, 53 cervical intervertebral discs of nine preoperative patients with neck and shoulder/arm pain scheduled for discectomy (five females, four males; mean age: 47.1 ± 8.4 years; range: 36-58 years) were included for biochemical analysis in this retrospective study. The patients underwent 3T magnetic resonance imaging (MRI) including biochemical imaging with dGEMRIC and morphological, sagittal T2 weighted (T2w) imaging. Cervical IVDs were rated using an MRI based grading system for cervical IVDs on T2w images. Region-of-interest measurements were performed in the nucleus pulposus (NP) and annulus fibrosus (AF) and a dGEMRIC index was calculated. Our results demonstrated that IVDs scheduled for discectomy showed significantly lower dGEMRIC index compared to IVDs that did not require surgical intervention in NP and AF (NP: 898.4 ± 191.9 ms vs. 1,150.3 ± 320.7 ms, p = 0.008; AF: 738.7 ± 183.8 ms vs. 984.6 ± 178.9 ms, p = 0.008). For Miyazaki score 3, the dGEMRIC indices were significantly lower in IVDs scheduled for surgery compared to non-operated discs for NP (p = 0.043) and AF (p = 0.018). In conclusion we could demonstrate that biochemical imaging with dGEMRIC is feasible in cervical IVDs. Significantly lower dGEMRIC index suggested GAG depletion in degenerated cervical IVD, scheduled for discectomy. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1824-1830, 2017.

// Marcel A. Kamp 1 , Igor Fischer 2 , Julia Buhner 1 , Bernd Turowski 3 , Jan Frederick Cornelius 1 , Hans-Jakob Steiger 1 , Marion Rapp 1 , Philipp J. Slotty 1 , Michael Sabel 1 1 Department of Neurosurgery, Medical Faculty, Heinrich-Heine-University, Dusseldorf, D-40225 Dusseldorf, Germany 2 Division of Informatics and Statistics, Department of Neurosurgery, Medical Faculty, Heinrich-Heine-University, Dusseldorf, D-40225 Dusseldorf, Germany 3 Institute for Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, D-40225 Dusseldorf, Germany Correspondence to: Marcel A. Kamp, email: marcelalexander.kamp@med.uni-duesseldorf.de Keywords: 5-aminolevulinic acid, cerebral metastases, recurrence, in-brain-progression, overall survival Received: March 30, 2016 Accepted: July 19, 2016 Published: August 22, 2016 ABSTRACT Aim of the present study was to analyze the oncological impact of 5-ALA fluorescence of cerebral metastases. A retrospective analysis was performed for 84 patients who underwent 5-ALA fluorescence-guided surgery of a cerebral metastasis. Dichotomized fluorescence behavior was correlated to the histopathological subtype and primary site of the metastases, the degree of surgical resection on an early postoperative MRI within 72 hours after surgery, the local in-brain-progression rate and the overall survival. 34/84 metastases (40.5%) showed either strong or faint and 50 metastases (59.5%) no 5-ALA derived fluorescence. Neither the primary site of the cerebral metastases nor their subtype correlated with fluorescence behavior. The dichotomized 5-ALA fluorescence (yes vs. no) had no statistical influence on the degree of surgical resection. Local in-brain progression within or at the border of the resection cavity was observed in 26 patients (30.9%). A significant correlation between 5-ALA fluorescence and local in-brain-progression rate was observed and patients with 5-ALA-negative metastases had a significant higher risk of local recurrence compared to patients with 5-ALA positive metastases. After exclusion of the 20 patients without any form of adjuvant radiation therapy, there was a trend towards a relation of the 5-ALA behavior on the local recurrence rate and the time to local recurrence, although results did not reach significance anymore. Absence of 5-ALA-induced fluorescence may be a risk factor for local in-brain-progression but did not influence the mean overall survival. Therefore, the dichotomized 5-ALA fluorescence pattern might be an indicator for a more aggressive tumor.

The surgical resection of cerebral metastases is one key element in a multimodal therapy of brain oligometastatic patients. Standard surgery alone is often not sufficient to achieve local control. Various reasons have been discussed including microscopic and macroscopic tumor rests after surgery and different growth patterns of cerebral metastases: In this review, we assessed the surgical standard technique and then analyzed the growth pattern of cerebral metastases and discussed its oncologic impact and new strategies in the surgical management of cerebral metastases. A major percentage of cerebral metastases are not sharply delimitated but show an irregular tumor-brain interface or even an infiltrative growth pattern. Different patterns of adjacent brain invasions have been described and may correlate with the prognosis of patients with cerebral metastasis. Even metastases of the same histological subtype and the same origin show a heterogeneous brain invasion pattern. Future therapeutic strategies might have to take this heterogeneity into account. An infiltrative growth pattern of cerebral metastases might be one reason for their extraordinary high local recurrence rate and might have an influence on the individual overall survival. An intraoperative detection of residual tumor and development of more radical surgical techniques is therefore an important neurooncological challenge and might result in better tumor control. Supramarginal resection of cerebral metastases is a promising approach.

UNLABELLED The aim of this study was to assess the clinical value of O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET in the initial diagnosis of cerebral lesions suggestive of glioma. METHODS In a retrospective study, we analyzed the clinical, radiologic, and neuropathologic data of 174 patients (77 women and 97 men; mean age, 45 ± 15 y) who had been referred for neurosurgical assessment of unclear brain lesions and had undergone (18)F-FET PET. Initial histology (n = 168, confirmed after surgery or biopsy) and the clinical course and follow-up MR imaging in 2 patients revealed 66 high-grade gliomas (HGG), 77 low-grade gliomas (LGG), 2 lymphomas, and 25 nonneoplastic lesions (NNL). In a further 4 patients, initial histology was unspecific, but during the course of the disease all patients developed an HGG. The diagnostic value of maximum and mean tumor-to-brain ratios (TBR(max/)TBR(mean)) of (18)F-FET uptake was assessed using receiver-operating-characteristic (ROC) curve analyses to differentiate between neoplastic lesions and NNL, between HGG and LGG, and between high-grade tumor (HGG or lymphoma) and LGG or NNL. RESULTS Neoplastic lesions showed significantly higher (18)F-FET uptake than NNL (TBR(max), 3.0 ± 1.3 vs. 1.8 ± 0.5; P < 0.001). ROC analysis yielded an optimal cutoff of 2.5 for TBR(max) to differentiate between neoplastic lesions and NNLs (sensitivity, 57%; specificity, 92%; accuracy, 62%; area under the curve [AUC], 0.76; 95% confidence interval [CI], 0.68-0.84). The positive predictive value (PPV) was 98%, and the negative predictive value (NPV) was 27%. ROC analysis for differentiation between HGG and LGG (TBR(max), 3.6 ± 1.4 vs. 2.4 ± 1.0; P < 0.001) yielded an optimal cutoff of 2.5 for TBR(max) (sensitivity, 80%; specificity, 65%; accuracy, 72%; AUC, 0.77; PPV, 66%; NPV, 79%; 95% CI, 0.68-0.84). Best differentiation between high-grade tumors (HGG or lymphoma) and both NNL and LGG was achieved with a TBR(max) cutoff of 2.5 (sensitivity, 79%; specificity, 72%; accuracy, 75%; AUC, 0.79; PPV, 65%; NPV, 84%; 95% CI, 0.71-0.86). The results for TBR(mean) were similar with a cutoff of 1.9. CONCLUSION (18)F-FET uptake ratios provide valuable additional information for the differentiation of cerebral lesions and the grading of gliomas. TBR(max) of (18)F-FET uptake beyond the threshold of 2.5 has a high PPV for detection of a neoplastic lesion and supports the necessity of an invasive procedure, for example, biopsy or surgical resection. Low (18)F-FET uptake (TBR(max) < 2.5) excludes a high-grade tumor with high probability.

Dysfunction of neuronal signal processing and transmission occurs after subarachnoid hemorrhage (SAH) and contributes to the high morbidity and mortality of this pathology. The underlying mechanisms include early brain injury due to elevation of the intracranial pressure, disruption of the blood-brain barrier, brain edema, reduction of cerebral blood flow, and neuronal cell death. Direct influence of subarachnoid blood metabolites on neuronal signaling should be considered. After SAH, some metabolites were shown to directly induce disruption of neuronal integrity and neuronal signaling, whereas the effects of other metabolites on neurotoxicity and neuronal signaling have not yet been investigated. Therefore, this mini-review will discuss recent evidence for a direct influence of subarachnoid blood and its metabolites on neuronal function.

Controversy exists about the influence of intracranial injuries in mild traumatic brain injury (mTBI) on quality of life (QoL). Some patients do not fully recover from mTBI and experience neurocognitive impairment and reduction in quality of life. We evaluated the influence of structural brain damage on QoL and employment status (ES) after mTBI.In a partially prospective design we evaluated QoL using Short-Form-36 (SF36) and current ES three years after trauma in 36 patients with mTBI in a matched pair design with two groups of 18 patients each with and without structural brain damage.Both groups showed a reduction in physical (Physical Functioning, Role Physical, Bodily Pain and General Health) and emotional parameters (Vitality, Social Functioning, Role Emotional and Mental Health) without significant difference between both groups (p = 0.305, p = 0.406, p = 0.624, p = 0.720, p = 0.934, p = 0.282, p = 0.811 and p = 0.270 respectively). ES was independent of structural brain damage and an influential factor for QoL.MTBI specific QoL assessment including focus on ES is necessary to identify patients at risk for impaired recovery. Structural brain injury as seen on CT scan is not useful as a prognostic tool to predict QoL or ES after mTBI.

Differential diagnosis of unclear contrast-enhancing cerebral lesions includes cerebral metastases as well as malignant glioma. In the majority of cases, a definite preoperative diagnosis by neuroradiological assessment alone cannot be made. Since the introduction of 5-ALA-induced fluorescence-guided resection in the treatment of glioblastoma (GBM), the preoperative putative diagnosis of metastasis vs. GBM triggers a specific preoperative preparation of the patients. We analyzed the patient population with known cancer outside the central nervous system who underwent surgery for an assumed cerebral metastasis and for whom the intraoperative diagnosis was corrected to a malignant glioma. Retrospective analysis of patients with a known primary cancer who were operated on for an assumed cerebral metastasis, which turned out to be a GBM. The patients were treated at our center between January 2008 and June 2011. We identified ten patients who underwent surgery for an assumed cerebral metastasis and for whom the diagnosis was corrected intraoperatively to a malignant glioma by frozen section. The median age was 68 years (41–82 years). The female-to-male ratio was 2:8. In all patients, the final histopathological analysis of the intracerbral tumors revealed a glioblastoma, while the patients suffered from diverse primary carcinomas. A malignant glioma should always be considered as a differential diagnosis of an unclear contrast-enhancing cerebral lesion even for patients with a known malignancy. Furthermore, we make the case for a more liberal indication for 5-ALA.

Background Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. Objective To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. Methods We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. Results For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. Conclusion Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

Patients requiring anterior–posterior thoracic spine stabilization and suffering from concomitant cardiopulmonary disease are at increased risk to develop procedure-related complications. In order to reduce cardiopulmonary complications, the efficacy of a posterolateral transpedicular approach for 360-degree fusion was investigated. Fourteen consecutive patients presenting with spinal cord compression from osteoporotic, metastatic and tuberculotic fractures were treated. Spinal cord decompression was achieved by laminectomy, facetectomy and corpectomy with subsequent posterior instrumented fusion using a screw–rod system. The procedure was successfully performed in 14 high-risk patients. Preoperatively, all patients presented with thoracic and lower back pain and nine patients with a paraparesis (Frankel grade C). The implants were introduced monoportally or biportally. In all cases, neurological symptoms moderately improved. The posterolateral transpedicular approach might be a safe, less-invasive and efficient alternative to anterior–posterior fusion. However, biomechanic efficacy and long-term outcome as compared to the transthoracic technique remains to be studied in a larger patient cohort.

As a result of the demographic shift in western societies, the mean age at presentation of patients suffering from chronic subdural hematomas (cSDH) is increasing. Therapeutic strategies, surgical and non-surgical, need to be reevaluated and adapted accordingly. Age is considered to be a positive risk factor for a higher perioperative morbidity and mortality. The purpose of this study is to determine if old age (≥85 years) should be seen as a contraindication for surgical treatment. Two groups (56 patients each) with cSDH over and below 85 years of age from a single neurosurgical department with well-defined surgical treatment guidelines were retrospectively analyzed. Clinical characteristics of the patients, localization, treatment, prior medication, and complications were compared. Outcome was measured by clinical improvement postoperatively and by the Glasgow Outcome Scale (GOS) at 1 month after surgery. Age ≥85 years was associated with higher GOS 1 month after surgery (p = 0.038). 51.8% (58) of all patients had a complete neurological recovery postoperatively, and 74% (43) of these patients were ≥85 years. Elderly patients suffered from a significantly higher complication rate (p

MRI offers perfect visualization of spondylotic stenosis of the cervical spine, but morphologic imaging does not correlate with clinical symptoms and postoperative recovery after decompression surgery. In this prospective study, we investigated the role of 18F-FDG PET in patients with degenerative stenosis of the cervical spinal cord in relation to postsurgical outcome. Methods: Twenty patients with monosegmental spondylotic stenosis of the middle cervical spine (C3/C4 or C4/C5) showing intramedullary hyperintensity on T2-weighted MRI and clinical symptoms of myelopathy (myelopathic patients) were investigated by 18F-FDG PET. Maximum standardized uptake values (SUVmax) were measured at all levels of the cervical spine (C1–C7). Decompression surgery and anterior cervical fusion were performed on all patients, and clinical status (Japanese Orthopedic Association [JOA] score) was assessed before and 6 mo after surgery. The 18F-FDG data of 10 individuals without cervical spine pathology were used as a reference (controls). Results: The myelopathic patients showed a significant decrease in 18F-FDG uptake in the area of the lower cervical cord, compared with the control group (C7 SUVmax, 1.49 ± 0.18 vs. 1.71 ± 0.27, P = 0.01). Ten myelopathic patients exhibited focally increased 18F-FDG uptake at the level of the stenosis (SUVmax, 2.27 ± 0.41 vs. 1.75 ± 0.22, P = 0.002). The remaining 10 patients showed inconspicuous 18F-FDG uptake at the area of the stenosis. Postoperatively, the patients with focally increased 18F-FDG accumulation at the level of stenosis showed good clinical recovery and a significant improvement in JOA scores (13.6 ± 2.3 vs. 9.5 ± 2.5, P = 0.001), whereas no significant improvement was observed in the remaining patients (JOA score, 12.0 ± 2.4 vs. 11.6 ± 2.5, not statistically significant). Multiple regression analysis identified the presence of focally increased 18F-FDG uptake at the level of the stenosis as an independent predictor of postoperative outcome (P = 0.002). Conclusion: The results suggest that regional changes in 18F-FDG uptake have prognostic significance in compression-induced cervical myelopathy that may be helpful in decisions on the timing of surgery.

Object Five-aminolevulinic acid–mediated photodynamic therapy (ALA/PDT) can improve the clinical outcome in patients suffering from glioblastoma. Besides direct phototoxicity, additional mechanisms may contribute. Therefore, the authors studied the influence of ALA/PDT on glioblastoma's migratory and invasive behavior in a human glioma cell spheroid model. Methods Glioma spheroids were grown from human U373 and A172 cell lines. After ALA/PDT of spheroids, the authors assessed the migration of tumor cells and their capacity to invade a collagen matrix, as well as changes in their viability, morphology, and expression of matrix metalloproteinases (MMPs). Results The authors found that ALA/PDT caused long-lasting, nearly complete suppression of glioma cell migration and matrix invasion compared with nontherapeutic controls, including either irradiation or incubation with ALA only. Although ALA/PDT induced tumor cell apoptosis, suppression of migration/invasion was not simply due to phototoxicity because 50% of tumor cells remained vital throughout the observation period. Moreover, the morphology of ALA/PDT-treated cells changed significantly toward a polygonal, epithelial-like appearance, which was associated with alterations in the actin cytoskeleton. Furthermore, downregulation of MMP-7 and -8 was observed after treatment whereas other MMPs remained unchanged. Conclusions In addition to directly eliminating glioma cells through apoptosis, ALA/PDT alters their invasiveness, possibly due to the effects on the cytoskeletal organization and MMP expression.

The optimal management of subtotally resected or recurrent malignant meningiomas remains controversial. We evaluated the efficacy of linear accelerator (LINAC) radiosurgery for atypical and anaplastic meningiomas after incomplete resection or treatment of recurrences. Between August 1990 and December 2003, 16 patients with 28 meningiomas WHO II and III were treated by stereotactic LINAC radiosurgery at our institution. The median radiological follow-up was 60.3 months, respectively (range: 7.2–173.9 months). Fourteen tumors in nine patients were classified as WHO II and 14 tumors in seven patients as WHO III. The median surface dose was 14 Gy (range: 10–15 Gy) with a median tumor volume of 4.8 ml (range: 0.51–51.4 ml). Clinical condition improved in four patients, remained unchanged in nine and deteriorated in one. Tumor shrinkage was seen in eight of 28 meningiomas and a stable disease in 12. Eight of 28 meningiomas showed local tumor progression. The overall tumor control rate (TCR) was 84%, 70%, 70% after 3, 5, 10 years. According to grading the corresponding TCR after 3, 5, 10 years was 91%, 81%, 81% for grade II and 77%, 60%, 60% for grade III meningiomas. Overall progression-free survival (PFS) was 74%, 67%, 58% after 3, 5, 10 years. According to grading the PFS after 3, 5, 10 years was 88%, 75%, 75% for grade II meningiomas and 57%, 57%, 43% for grade III meningiomas. Our results show the efficacy and safety of LINAC radiosurgery for incompletely resected or recurrent malignant meningiomas with a relatively high local tumor control and low morbidity.

A sequence of 11 consecutive arginine residues (11R) is one of the best protein transduction domains for introducing proteins into cell membranes. Heme-oxygenase-1 (HO-1) is involved in heme catabolism and reduces the contractile effect of hemoglobin after subarachnoid hemorrhage (SAH). Therefore, we constructed 11R-fused HO-1 protein to achieve successful transduction of the protein into the cerebral arteries and examined the therapeutic effect of the 11R-HO-1 protein for cerebral vasospasm (CV) after SAH. We injected the 11R-HO-1 protein into the cisterna magna of male rats and, several hours after the injection, performed immunofluorescence staining and western blotting analysis of the rat basilar arteries (BAs) to determine transduction efficacy. We also assessed intraarterial HO-1 activity as cGMP (cyclic guanosine 3′, 5′-cyclic monophosphate) accumulation in SAH and determined whether protein transduction of 11R-HO-1 quantified the therapeutic effect in a rat double-hemorrhage model of SAH. The BAs expressed significantly more HO-1 in the group injected with 11R-HO-1 (3.56±0.54 (11R-HO-1) versus control (saline)), and transduction of 11R-HO-1 resulted in higher activity (>3.25-fold) in rat BAs with SAH. Moreover, the results of the rat double-hemorrhage model showed that the 11R-HO-1 protein significantly attenuated CV after SAH (317.59±23.48 μm (11R-HO-1) versus 270.08±14.66 μm (11R-fused enhanced green fluorescent protein), 252.05±13.95 μm (saline), P

Objective With the use of fluorescence-guided resection with 5-aminolevulinic acid (5-ALA), the rate of complete resection of the contrast-enhancing part of malignant gliomas could be increased from 36% to 65%. Because the visualization of 5-ALA-induced fluorescence depends on a sufficient exposure to fluorescent light, residual tumor tissue in deep-seated resection cavities might not be detected. In addition, subcortical parts of a large spherical tumor might not be visualized, owing to a tangential position at the periphery of the microscopic field. With the availability of a specially designed endoscope with the capability to visualize 5-ALA fluorescence, we investigated the impact of this new technique on the visualization of residual glioma tissue. Methods A standard dose of 5-ALA 20 mg/kg was administered to 9 patients with deep-seated contrast-enhancing brain tumors 3 hours before surgery. A standard surgical exposure was performed and supplemented by the use of a specially designed endoscope with an option of 5-ALA fluorescence guidance. After microscopic visualization of the surgical cavity, endoscopic visualization was employed. If additional fluorescence tissue was detected, microscopic visualization was performed. Detected remnants of the tumor were removed and evaluated by histologic examination. Results In all cases, fluorescence-guided endoscopic visualization identified 5-ALA-positive tissue not sufficiently exposed by conventional microscopic visualization. In 8 patients, histopathologic examination confirmed residual tumor tissue; in 1 patient, the endoscopic visualized tissue was classified as radiation necrosis. In this patient, the tumor was completely ALA negative microscopically. Conclusions As an additional instrument, fluorescence-guided endoscopic visualization might help to overcome technical limitations of the conventional microscopic exposure of 5-ALA-positive tumor tissue. The false-positive 5-ALA tissue indicates that endoscopic visualization may overestimate the amount of tumor, so further analyses to ascertain the sensitivity and specificity of this technique are required.

The aim of open surgery of cerebral aneurysms is to minimise the risk of infarction due to poor position of a clip while still securing the aneurysm from rebleeding. Whilst digital subtraction angiography (DSA) remains the gold standard for precise evaluation of the result, its invasiveness, risk of thromboembolic infarction, availability and time-consumption pose a significant limitation, and overall it is rarely used. The goal of the present study was to analyse the feasibility of intraoperative B-mode Duplex ultrasound in combination with Doppler sonography (DDS) to evaluate this issue.A total of 44 aneurysms in 40 patients were investigated intraoperatively via B-mode and power Duplex sonography after clip positioning in a prospective setting. Data were then compared to postoperative angiography.In 38 cases DDS allowed for visualisation of aneurysm localisation, neck and diameter, as well as associated vessels, in accordance to preoperative DSA. This was confirmed by Duplex sonography in 94.7%. Further evaluation of each associated vessel after clip positioning was then enabled by Doppler sonography in 84.8%. Visualisation in terms of B-mode sonography was not successful in six cases due to multiple clips.DDS is an additional tool for immediate evaluation of clipping performance intraoperatively and can be used in simple cases with reliable results. In six cases Doppler-/Duplex-sonography did not illustrate the clipping result sufficiently. It is not yet able to replace DSA in aneurysms with complex configuration.

The aim of the study was to compare presurgical (18)F-fluoroethyl-L: -tyrosine ((18)F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas.(18)F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for (18)F-FET or Gd and checked for 5-ALA fluorescence. (18)F-FET uptake with a mean tumour to brain ratio ≥1.6 was rated as positive.Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, (18)F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, (18)F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on (18)F-FET PET.There are differences between (18)F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. (18)F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning.

Morbidity and mortality conferences (M&MC) are a traditional part of residency programs in a large number of countries to increase the training quality. The purpose of the present publication is to report our experience with a monthly M&MC over a 5-year period and, in particular, to describe the methods to identify critical cases, the system of analysis, classification of morbidity and mortality, and the resulted impact. Monthly identification of M&M was done through a system of electronically coding hospital course at the time of discharge. Morbidity was classified as moderate if sequels resolved within 3 months or otherwise as severe. Morbidity included management complications not directly related the neurosurgical procedure, such as pneumonia or thromboembolism. Mortality was classified as related to surgery or unrelated, e.g., after severe trauma. Mortality in relation to surgery was subclassified in terms of causal relation or not. Statistical comparison of incidence rates was calculated statistically. Overall management morbidity rate was 7.1%, and mortality with causal relation to surgery was 0.38%. The leading cause of morbidity was additional neurological deficit (25%) followed by postoperative hemorrhage (23%) and second unplanned surgery due to incomplete result of the primary procedure (14%). Overall, the monthly incidence varied without a discernable annual pattern. Over the years, there were only a handful of guideline updates triggered by incidents. Our system to identify complication proved to be reliable. During the study period, the M&MC developed into a well-accepted instrument of quality control and problem-oriented teaching, but the impact on quality improvement remained questionable.

Background Microscope-based intraoperative near-infrared indocyanine green (ICG) videoangiography is useful as an adjunct to intra- or postoperative digital subtraction angiography (DSA) in aneurysm surgery. Objective To evaluate intraoperative ICG videoangiography for surgery of arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs). Methods Seventeen patients undergoing surgical resection of intracranial AVM or AVF were enrolled into this prospective evaluation. ICG videoangiography sequences were analyzed with regard to transit times to differentiate between arterial, early venous, capillary, and venous phase as well as early passage (fistula) and delayed appearance (ischemia). ICG videoangiography was compared with pre- and postoperative angiography. Results Forty-six ICG videoangiographies were performed in 17 operative procedures. In 41 ICG investigations image quality and spatial resolution were excellent to analyze arterial, early venous, capillary, and venous phase. In 2 cases ICG videoangiography provided additional information to change the surgical strategy. With the exception of one case only, the postoperative angiogram corresponded to the last ICG examination performed after the resection. No side effects related to ICG injection were observed. In one patient with a deep thalamic AVM the final ICG investigation was inconclusive owing to insufficient illumination of the deep surgical field. Conclusion Microscope-integrated repetitive ICG videoangiography during AVM and dAVF surgery is fast, easy to perform, and safe. This simple and safe real-time method is a useful additional tool that can potentially lower the surgical risk in complex AVMs and help avoid missed residuals.

Object Spinal cordectomy has recently become more important in the treatment of end-stage posttraumatic or postoperative syringomyelia and arachnopathy as a last resort to manage ascending neurological dysfunction, spasticity, and pain in paraplegic patients. The aim in this study was to confirm a clinical benefit in strict indications for cordectomy. Methods Between February 2000 and September 2007, 15 spinal cordectomies were performed at the Department of Neurosurgery, Cantonal Hospital, St. Gallen. Indications for treatment were end-stage myelopathies caused by syringomyelia, tethered cord syndrome, and arachnopathy with progressive spasticity and pain or progressive upper-level neurological deficits related to the tethered cord syndrome. All patients had severe motor and sensory deficits with no residual voluntary function below the affected level. Results Fourteen of 15 patients showed stabilization or even an improvement in motor and sensory function. Four patients suffered from progressive spasticity and 3 from deterioration due to pain. There were no other adverse surgical events. Conclusions Cordectomy can be a useful instrument to preserve functions of the upper extremities and to improve spasticity and pain in patients with severe myelopathy and tethered cord, syringomyelia, or arachnopathy of various etiologies.

The goal of the study was to analyse retrospectively the impact of risk factors for subarachnoid haemorrhage (SAH) on the size of ruptured intracranial aneurysms in order to identify variables that might influence the discrepancy between average sizes of ruptured and unruptured aneurysms.The records and angiographies of 373 patients treated at our centre due to aneurysmal SAH between 2004 and December 2008 were retrospectively analysed. Modifiable and non-modifiable risk factors for SAH were correlated with exact measurement of aneurysm size using three-dimensional rotational digital subtraction angiographies (3D-DSA).Average maximum aneurysm diameter in patients with combined history of hypertension and cigarette smoking was 5.47±3.22 mm (95% CI 4.71 to 6.24); thus, significantly smaller (p0.001) than in patients with hypertension only (6.27±3.28 mm, 95% CI 5.75 to 6.78), with cigarette smoking only (7.61±4.29 mm, 95% CI 6.43 to 8.79) and patients with no history for risk factors (8.08±4.73 mm, 95% CI 6.96 to 9.21). Odds ratio (OR) for aneurysm size less than 7 mm in patients with combined hypertension and cigarette smoking was 3.63 (95% CI 1.78 to 7.42), 3.09 (95% CI 1.95 to 4.92) in patients with hypertension only and 1.02 (95% CI 0.64 to 1.62) in patients with cigarette smoking only.The present analysis demonstrates a distinct correlation between hypertension, smoking and the size of ruptured aneurysms in SAH patients. Arterial hypertension and cigarette smoking appear to destabilise cerebral aneurysms' growth. Our data strongly suggest that these factors should also be considered when treatment indications for small unruptured aneurysms are discussed.

The aim of this preliminary report was to assess glucose metabolism in the cervical spine of patients with chronic compressive myelopathy by using FDG PET.Ten patients with monosegmental chronic degenerative stenosis and local cord compression of the upper/middle cervical spine with signs of myelopathy on MRI and 10 control patients without known cervical abnormalities were investigated by FDG PET. Maximum standardised uptake values (SUV(max)) were measured at all levels of the cervical spine (C1-C7).While the controls showed the typical pattern of homogeneous linear FDG uptake along the entire cervical cord, the patients with chronic compressive myelopathy had a normal glucose utilisation only above the level of stenosis and a significant decrease in FDG uptake below their individual level of cord compression. This may be caused by atrophy of anterior grey horn cells and the loss of glucose-consuming neurons below the level of cord compression.FDG PET of the spine of patients with chronic compressive myelopathy may be helpful to determine the stage and severity of cervical myelopathy.

Ependymoma is the third most common brain tumor in children. Subsets of ependymomas, in particular RELA fusion-positive supratentorial ependymomas and posterior fossa type A ependymomas, are associated with frequent recurrence and dismal outcome. Neurosurgical resection and radiotherapy are the main therapeutic options, while response to conventional chemotherapy is limited. We aimed to establish a high-throughput drug screening (HTS) pipeline for comprehensive individualized testing of patient-derived primary cultures to identify novel therapeutic targets for ependymomas. Ependymoma primary cultures (n=6) were established following tumor resection and underwent HTS in 1536-well plates to allow large-scale drug screening despite limited cell numbers. We generated dose-response data with 9 dilution steps (dose range 32.5nM to 25µM) for a clinical inhibitor library (n=196) comprising established chemotherapeutic agents and novel anti-cancer compounds currently in phase III and IV studies. The Infinium MethylationEPIC Array was used to characterize primary tumors and matched primary cultures genomically and epigenetically. DNA methylation and copy number profiles revealed that short-term primary cultures faithfully recapitulate the genomic and epigenetic landscape of the corresponding primary tumors. Comparison of drug response data from ependymomas, other pediatric brain tumors (n=25) and controls (i.e. non-neoplastic neural progenitor cells) confirmed extraordinary chemoresistance of ependymomas but also revealed promising selectively active drugs, such as neratinib, an irreversible ERBB2 inhibitor. Thus, our data demonstrate the feasibility of HTS in primary cultures derived from pediatric brain tumors and provide preclinical evidence suggesting inhibition of ERBB2 as a promising therapeutic option in a subset of otherwise highly chemoresistant ependymomas.

Neurosurgery and medicine in general are increasingly dominated by economic factors and considerations. Physicians themselves have partially adopted economic terminology, although they rarely have a profound knowledge of economics. Today game theory is one of the most important factors driving microeconomics, which is the competition for limited resources within a small group of individuals. The purpose of this article is to give a short introduction to game theory and its application to the healthcare system. The Prisoner's Dilemma considers strategies between two persons. In the classic version two burglars are caught. Each could confess and be released from jail if the other does not confess--who will then get a long term in prison. If both confess, both get an intermediate time in jail, and if no one confesses, both get a mild sentence. Wanting to be released from jail, they both confess and get the intermediate term in prison. This remarkable result, initially described by John von Neumann in 1928 and showing that individually rational actions can result in both persons becoming worse off, had a great impact on modern social science. Other scenarios are more complex. The Nash Equilibrium is a wider concept. If there is a set of strategies with the property that no player can benefit by changing his strategy while the other players keep their strategies unchanged, then that set of strategies and the corresponding payoffs constitute the Nash Equilibrium. Another concept particularly important in sociology is the Pareto criterion. If no one can be made better off without making somebody else worse off, then that outcome is Pareto optimal. Respecting these basic principles is a necessary precondition for successful deals and cooperative projects.

Objective Several recent investigations have demonstrated a significant influence of blood pressure variation during the immediate period after stroke. The present study was conducted to evaluate the effect of blood pressure, intracranial pressure and cerebral perfusion pressure variation on short-term outcome in patients after severe subarachnoid hemorrhage (SAH). Material and methods 105 patients suffering from severe SAH were included in the study. The Glasgow Coma Scale (GCS) Score and World Federation of Neurological Surgeons (WFNS) grading were used to describe the patients on admission, and the short-term outcome was assessed using the GCS and the Glasgow Outcome Scale (GOS) Score. In all patients, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were continuously recorded. For each recorded parameter (SBP, DBP, MAP, ICP and CPP) the first recorded value was defined as the baseline value (bas). The minimum (min), maximum (max) and average (mean) value was identified from all recorded values for each parameter and the range between minimum and maximum value was calculated (range). Based on the individual parameter range (absolute values) the variability of successive values was determined as the successive variation (sv). Finally, the values obtained were correlated to clinical outcome and analyzed statistically. Results In 105 patients the database offered an average of 330.4 single readings (median 318). SBPmax, and SBPrange were significantly lower in the group with an improving short-term GCS than in the group with constant or deteriorating GCS ( P=0.0079 and P=0.0006, respectively). SBPmin was significantly higher in the improved GCS group (P=0.0235). With regard to successive variation (SBPsv) we could not demonstrate a significant difference between both groups (mean SBPsv 15.7 vs. 14.7; P=0.1223), and no correlation with either GCS at discharge (P=0.91) or GOS at discharge (P=0.841) was detectable. There was no statistically significant difference in CPP and ICP between both outcome groups. Conclusion Systolic blood pressure levels and range appear to be of importance for the management of patients suffering from SAH and may influence patient outcome.

OBJECTIVE: Exact intraoperative localization of pathologies in spinal and peripheral nerve surgery is not easily achieved. In spinal surgery, intraoperative fluoroscopy is the common method for identification of the level affected. It seldom visualizes the pathology itself and is prone to error in identifying anatomic disorders and superimposing structures. In peripheral nerve surgery, intraoperative fluoroscopy is of little value. The present technical study was conducted to evaluate the feasibility of using a preoperative computed tomography-guided needle marking system, which was previously developed for use in gynecology. The goal was to reduce intraoperative localization error and radiation exposure to patients and operating room personnel. METHODS: We used a flexible hooked-wire needle marking system, which has previously been used for preoperative marking of breast lesions, to localize and tag spinal and peripheral nerve pathologies. Marking was carried out under computed tomographic control before surgery. Seven illustrative cases were chosen for this report: 6 patients with disorders of the spine and 1 patient with a peripheral nerve schwannoma. RESULTS: No adverse reactions, aside from minor discomfort, were observed in this study. In all cases, the needle could be used as a reliable guide for the surgical approach and led directly to the pathology. In no case was additional intraoperative fluoroscopy needed. The level of radiation exposure to the patient as a result of computed tomography-based marking was similar to or less than that encountered in conventional intraoperative x-ray localization. Radiation exposure to the operating room personnel was eliminated by this method. CONCLUSION: Preoperative marking of spinal level or peripheral nerve pathologies with a flexible hooked-wire needle marking system is feasible and appears to be safe and useful for neurosurgical spinal and peripheral procedures.

Spinal solitary epidural cavernous angiomas are rare benign vascular malformations, which occur even less frequently in children than in adults. It is uncommon to find such lesions without adjacent vertebral involvement. Occasionally, these lesions can lead to neurological symptoms through growth or due to intralesional hemorrhage. In this report the authors describe 2 children presenting with acute symptoms and neurological deficits caused by hemorrhage within solitary spinal epidural cavernous angiomas. A 13-year-old girl and a 9-year-old girl, previously healthy, were admitted to the authors' department due to acute radicular pain and neurological deficits. In both cases MR imaging revealed a solitary epidural mass with signs of bleeding and compression of the spinal cord. Complete resection of the lesion via a dorsal approach was performed in both patients. The histological examination of the lesions revealed the characteristic structures of a cavernous angioma with hemosiderin deposits and acute hemorrhage. Both patients recovered fully after surgical removal of the lesions. Review of the literature confirmed that spinal epidural cavernous angiomas are extremely rare in the pediatric patient population, described currently in only 2 instances, but without acute hemorrhage. These cases suggest that epidural cavernous angiomas also have to be considered in the pediatric patient population in the differential diagnosis of intraspinal lesions with acute or progressive neurological symptoms. Microsurgical resection of these cavernous malformations is an effective and curative treatment option.

The highly eloquent surroundings of brainstem arteriovenous malformations (AVMs) present particular surgical challenges. In the present pilot study we tried to examine whether to occlude the draining vein after control of major feeding arteries and then to coagulate the nidus retrogradely might be a viable concept for brainstem AVMs instead of the traditional perinidal dissection. A total of five patients harbouring pontine or mesencephalic AVMs were treated at our institution between February 2007 and August 2008. Three of them presented after haemorrhage. In two instances, partial endovascular obliteration was performed prior to surgery. Following exposure and control of major feeders, the principal draining vein was clamped to test tolerance. In none of the cases was major stasis and bleeding from the nidus seen. The draining vein was subsequently coagulated and then stepwise shrinking by retrograde coagulation of the nidus was done. The coagulated nidus was left in place. The procedure was technically successful in all cases and no major postoperative complication related to the procedure was seen. Control angiography confirmed complete occlusion in all cases. Due to the usually small size of brainstem AVMs, retrograde coagulation of the nidus without additional resection can be a feasible approach in order to avoid additional damage by circumferential dissection.

Pineal cysts are benign and often asymptomatic intracranial entities. Occasionally they can lead to neurological symptoms through growth or due to intracystic hemorrhage. The purpose of the current report is to describe their clinical characteristics and treatment options. In the current study, the authors illustrate the course of disease in 3 patients who developed neurological symptoms due to hemorrhage into a pineal cyst. Two of their patients had additional cerebral disease, and regular MR imaging examinations were conducted. This circumstance allowed documentation of growth and intracystic hemorrhage. After the occurrence of new neurological symptoms with severe headache, MR images showed a fluid-fluid interface due to intracystic hemorrhage. The third patient presented with acute triventricular hydrocephalus and papilledema due to aqueductal stenosis caused by intracystic hemorrhage. In all 3 cases, excision of the pineal cysts via an infratentorial/supracerebellar approach was performed. Histological examination revealed the characteristic structure of pineal cyst in all cases, with hemorrhagic residues in the form of hemosiderin deposits. All patients recovered fully after surgical removal of the cysts. Furthermore, resolution of occlusive hydrocephalus could be demonstrated in those cases with ventricular enlargement. Pineal cysts without neurological symptoms are often discovered as incidental findings on cranial MR images. In contrast, neurological symptoms such as severe headache, diplopia, or Parinaud syndrome, may occur as a result of pineal apoplexy due to intracystic hemorrhage. The authors' cases confirm that MR imaging can identify intracystic hemorrhage by a characteristic fluid-fluid interface. Their experience suggests that microsurgical resection of cysts may be an effective and curative treatment option.

Object Preliminary experience with the C-Port Flex-A Anastomosis System (Cardica, Inc.) to enable rapid automated anastomosis has been reported in coronary artery bypass surgery. The goal of the current study was to define the feasibility and safety of this method for high-flow extracranial-intracranial (EC-IC) bypass surgery in a clinical series. Methods In a prospective study design, patients with symptomatic carotid artery (CA) occlusion were selected for C-Port–assisted high-flow EC-IC bypass surgery if they met the following criteria: 1) transient or moderate permanent symptoms of focal ischemia; 2) CA occlusion; 3) hemodynamic instability; and 4) had provided informed consent. Bypasses were done using a radial artery graft that was proximally anastomosed to the superficial temporal artery trunk, the cervical external, or common CA. All distal cerebral anastomoses were performed on M2 branches using the C-Port Flex-A system. Results Within 6 months, 10 patients were enrolled in the study. The distal automated anastomosis could be accomplished in all patients; the median temporary occlusion time was 16.6 ± 3.4 minutes. Intraoperative digital subtraction angiography (DSA) confirmed good bypass function in 9 patients, and in 1 the anastomosis was classified as fair. There was 1 major perioperative complication that consisted of the creation of a pseudoaneurysm due to a hardware problem. In all but 1 case the bypass was shown to be patent on DSA after 7 days; furthermore, in 1 patient a late occlusion developed due to vasospasm after a sylvian hemorrhage. One-week follow-up DSA revealed transient asymptomatic extracranial spasm of the donor artery and the radial artery graft in 1 case. Two patients developed a limited zone of infarction on CT scanning during the follow-up course. Conclusions In patients with symptomatic CA occlusion, C-Port Flex-A–assisted high-flow EC-IC bypass surgery is a technically feasible procedure. The system needs further modification to achieve a faster and safer anastomosis to enable a conclusive comparison with standard and laser-assisted methods for high-flow bypass surgery.

Objective Intracisternal continuous therapy is a concept in the treatment of cerebral vasospasm after subarachnoid hemorrhage. The purpose of the current study was to investigate the effect of intracisternal nimodipine after induced vasospasm. Methods Sixty-five male Wistar rats were randomized into 4 groups: the control sham-operated group, the control subarachnoid hemorrhage-only group, and the treatment groups receiving 5 or 10 microL/hour of intracisternal nimodipine continuously for 5 days via subcutaneously implanted Alzet osmotic pumps (Durect Corp., Cupertino, CA). Vasospasm was analyzed 5 days later by means of digital subtraction angiography. Morphological examination of the brain parenchyma was performed using Nissl-staining, c-Fos immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling. Results Detailed analysis of the digital subtraction angiography was possible for 31 animals. Significant angiographic vasospasm was induced in the double hemorrhage-only group compared with the sham-operated group (P = 0.002). Among the 4 groups, there were statistically significant differences of the arterial vessel caliber as measured by digital subtraction angiography (P = 0.001, Kruskal-Wallis test). The treatment group receiving 5 microL/hour of nimodipine and the control sham-operated group demonstrated the largest intracranial artery diameters with a significant difference between control subarachnoid hemorrhage-only group and the treatment group receiving 10 microL/hour of nimodipine (P = 0.0328, Wilcoxon rank-sum test). Variation in vessel calibers, however, did not result in different brain tissue alterations, even when using sensitive markers for the induction of the stress response or apoptosis. Conclusion Intracisternal nimodipine lavage with 5 microL/hour, but not with 10 microL/hour leads to significant arterial relaxation. Further research is needed to elucidate the underlying cause of the decreasing nimodipine effect at higher dosage.

Objective Recent publications suggest that a combination of head-shaking and cisternal irrigation might reduce symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). The present clinical prospective randomized phase I/II study was initiated in order to analyze the prophylactic effect of intracisternal lysis in combination with kinetic treatment followed by intrathecal nimodipine lavage. Methods Twenty patients with aneurysmal SAH, WFNS grade 2 to 5 (GCS 13-3) and Fisher grade 3 or 4 were included in this prospective randomized study which had been approved by the local Ethics Research Committee. Following insertion of a ventricular drain, securing of the aneurysm by a microsurgical or endovascular route and the insertion of two lumbar catheters, intracisternal lysis with urokinase 120 000 IU/d was performed for 48 h in the patients of the study group. Intrathecal pressure was monitored by the second lumbar catheter. After intracisternal lysis, intrathecal nimodipine lavage was applied for 7 d. For comatose patients kinetic head-rotation was also performed. Vasospasm was clinically identified with a focus on delayed neurological deficits (DINDs) by daily transcranial Doppler (TCD), computerized tomography (CT), perfusion CT (pCT) and cerebral angiography (DSA). Results There was no DIND in the study group among the patients who were awake, while two DINDs occurred in the control group. The pooled TCD flow velocities over an average period of 14 d revealed no statistically significant difference between the groups. Vasospasm-related infarction on CT was seen in two patients of the control group. Evident vasospasm on DSA appeared in three patients of the study group compared with 7 patients in the control group. Moreover there was a neurological improvement in the study population as measured by mRS at 3-month follow-up (P=0.266). In two consecutive patients randomized to the study group a paresis of the lower extremities of unknown origin occurred. As a result of these complications the study was stopped in accordance with the local Ethics Research Committee guidelines. Conclusion A multimodal approach with translumbar lysis in combination with kinetic therapy followed by intrathecal nimodipine lavage proved to be effective against cerebral vasospasm and for clinical outcome. However, due to the observed complications with the occurrence of paraparesis in two patients of the study group the trial was stopped. Nevertheless, the promising preliminary results suggest a further development of the clinical protocol using a modified multimodal concept to prevent and treat cerebral vasospasm after severe SAH.

A total 17 fronto-mesial grade II and III gliomas among a total of 64 frontal grade II and III gliomas underwent surgical resection between January 2003 and June 2007. Eleven fronto-mesial gliomas originated from the anterior cingulate gyrus, while the others originated from the genu of the corpus callosum. None of the grade II or III gliomas originated from the gyrus rectus. Anterior cingulate gliomas exhibited distinct features with regard to presenting symptoms, MRI, histopathology and prognosis. Epilepsy was the dominant presenting symptom of anterior cingulate tumours. Five of the 11 gliomas had a sharp border on MRI. Four of the 11 were histopathologically classified as WHO grade II and seven as WHO grade III and an oligodendrocytic component was apparent in eight of the 11 specimens. Comparison of the post-operative survival with the entire set of frontal gliomas showed a trend that anterior cingulate tumours had a more favourable prognosis.

Symptomatic vascular compression of the medulla oblongata causing brainstem dysfunction is extremely rare. Only a few case reports documenting the clinical condition of patients, diagnostic features and therapeutic options are available in literature. The Medline search revealed with the present cases a total of 9 reports on patients with symptomatic vertebral artery compression to the brainstem. Out of these reports the observed symptoms comprise hypertension, hemiparesis, tetraparesis, hemihypaesthesia, pyramidal tract signs, central sleep apnea and vertigo. Moreover an overview of the various suggested and published microsurgical procedures is given. Based on the literature search basically 4 different microsurgical strategies are documented, the vessel mobilization, the vessel section with posterior fossa decompression, the autologous material inlay with posterior fossa decompression and the lateral vessel retraction assisted with Gore-Tex. Vascular compression causing brainstem deficits are particularly unusual in the young population. Two illustrative cases of young men with a symptomatic vertebral artery brainstem conflict who were treated microsurgically with vascular decompression are additionally discussed in the present article. The history, diagnostic features, microsurgical treatment and outcome of these patients are described in detail. As a conclusion these cases demonstrated that careful examination can serve to determine the diagnosis even in the young population microsurgical treated successfully. In conclusion the present review tries to provide an overview of the existent data on the variety of clinical, radiological and surgical features in patients with symptomatic vascular brainstem compression.

Object The authors of recent publications have suggested that a combination of cisternal irrigation and head-shaking therapy might reduce cerebral vasospasm after subarachnoid hemorrhage (SAH) and therefore improve outcome. The authors undertook this prospective nonrandomized Phase II study to analyze the effect of enhanced washout by lumboventricular irrigation in combination with head motion (lateral rotational therapy) on the clot clearance (CC) rate, development of cerebral vasospasm, and clinical outcome. Methods Forty patients with aneurysmal SAHs of World Federation of Neurosurgical Societies Grades II–V (Glasgow Coma Scale Scores 13–3) and Fisher Grade 3 or 4 were included in this study. The study and control groups each consisted of 20 patients. The protocol in the study group, after the aneurysm was secured and a ventricular drain inserted, included the insertion of 2 lumbar catheters for intrathecal irrigation with Ringer solution and intrathecal pressure monitoring. Moderate head rotation in a kinetic system was also applied and was continued for 5 days. The CC rate was monitored on daily computed tomography (CT) scans. Vasospasms were identified clinically with a focus on delayed ischemic neurological deficits (DINDs), daily transcranial Doppler (TCD) ultrasonography studies, and analysis of infarction rate on CT and cerebral angiography. The data obtained in both groups were statistically evaluated. Results There were no procedure-related complications. The overall CC rate did not differ significantly between the groups, but there was a trend toward accelerated resolution in the study group. During observation, a new neurological deficit developed in 1 patient (5%) in the study group and 4 patients (20%) in the control group. Ischemic areas on CT scans related to vasospasm were demonstrated in 2 patients (10%) in the study group and 6 patients (30%) in the control group. The incidence of angiographic vasospasm was approximately the same in both groups. The pooled TCD flow velocities measured over a period of 14 days showed lower mean values in the study group than in the control group (p = 0.00002). The clinical outcome in the study group as evaluated with the modified Rankin scale was better in the study group than in the control group after 3 (p = 0.008) and 6 (p = 0.005) months. Conclusions The present study demonstrates that a combination of lumboventricular lavage and mechanical head motion reduces vasospasm on TCD ultrasonography, the incidence of DIND, and secondary infarctions on CT and improves clinical outcome. No obvious effect could be found on the rate of angiographic vasospasm.

A number of publications suggest that there are seasonal influences on the incidence of subarachnoid hemorrhage (SAH). Most series agree on a peak incidence during springtime. Meteorological influences have been assumed to be obvious explanations for seasonal variations. Furthermore, the perceived clustering of the incidence of subarachnoid hemorrhage is also intuitively related to meteorological influences. The present study was initiated to determine whether specific meteorological conditions are related to the occurrence of SAH in the mild climatic zone of North Rhine Westphalia.We retrospectively examined 183 patients (107 women and 76 men) treated at our department between January 2003 and June 2005 for SAH that had occurred within the Düsseldorf metropolitan area. We correlated the date of SAH (Day 0) and of the week preceding the incident (Days -1, -3, -5, and -7) with the meteorological key parameters from Düsseldorf International Airport. Parameters analyzed were mean daily temperature (7C), relative humidity (%), barometric pressure (hPa), and weather condition (divided into 6 groups: clear, cloudy, rain, thunderstorms, snow, and not available).A relative peak incidence of SAH was found for the month of April. In addition, a diurnal rhythm with two peaks during morning and in the evening, and a statistically significant nadir during forenoon and midday was evident (P0.002). None of the average meteorological key parameters of the day of SAH differed from the annual average, and no general trends during the days preceding hemorrhage could be identified. Apparent clustering of the occurrence of SAH could not be related to short-term meteorological trends.The results of the present study demonstrate a trend toward a seasonal distribution in the incidence of SAH with a peak during spring in the metropolitan area of Düsseldorf. Furthermore, weather variables, such as temperature, barometric pressure, and humidity, were shown to be without influence on aneurysm rupture within the patient population. Therefore, the result indicates the need to validate further parameters in detail to isolate risk circumstances to achieve a risk pattern for patients with SAH.

Nonspecific incidental brain lesions (NILs) are being detected more frequently because of an increasing number of screening or research MRI scans of the brain, and their natural course is uncertain.In a prospective cohort study starting in 1999, we determined the outcomes of patients with incidental, nonenhancing, supratentorial, lobar, and small-volume (10 mL) lesions, depending on the findings of MRI and PET with the (18)F-labeled amino acid fluoroethyl-l-tyrosine ((18)F-FET). Patients with seizures, focal neurologic deficits, signs of local or systemic infection or inflammation, known brain disease, or any kind of previous cerebral treatment were excluded. Finally, 21 patients were eligible. MRI was performed in 19 of these patients because of nonspecific symptoms (such as headaches, dizziness, or sudden deafness), whereas 2 patients were healthy volunteers in MRI studies. Clinical follow-up and MRI scans were obtained at 4- to 6-mo intervals, and follow-up ranged from 3 to 8.5 y. Mean lesion-to-brain (L/B) ratios ofor=1.6 on (18)F-FET PET were rated as positive.Four different outcome groups were identified. In group A, 5 NILs regressed or vanished completely. All of these lesions were circumscribed on MRI, and (18)F-FET uptake was negative, with an L/B ratio of 1.2+/-0.2 (mean +/- SD). In group B, 10 NILs were stable, without growth. All of these lesions were circumscribed on MRI, and (18)F-FET uptake was negative (L/B ratio: 1.0+/-0.1). In group C, 2 NILs grew slowly over years, and an astrocytoma of World Health Organization (WHO) grade II was diagnosed after resection in each case. The lesions were circumscribed on MRI, and (18)F-FET uptake was negative (L/B ratios: 0.7 and 1.0). In group D, 4 NILs showed sudden and rapid growth, with clinical deterioration, and a high-grade glioma of WHO grade III or IV was diagnosed after resection in all cases. The lesions were diffuse on MRI, and (18)F-FET uptake was significantly increased (L/B ratio: 2.0+/-0.4) (P0.01 for group D vs. group A or group B).For NILs, a circumscribed growth pattern on MRI and normal or low (18)F-FET uptake on PET are strong predictors for a benign course, with the eventual development of a low-grade glioma. In contrast, NILs with a diffuse growth pattern on MRI and increased (18)F-FET uptake indicate a high risk for the development of a high-grade glioma.

BACKGROUND AND PURPOSE: The efficacy of intra-arterial administration of nimodipine (IAN) in patients with severe vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains unproved. The goal of the present study was to investigate the clinical effect and cerebral perfusion after IAN in patients with severe vasospasm refractory to hemodynamic treatment. MATERIALS AND METHODS: Twenty-six of 214 patients with aneurysmal SAH were included in the prospective study, approved by the local ethics committee. All patients met the criteria of medically refractory cerebral vasospasm. Effectiveness was monitored angiographically by digital subtraction angiography and by transcranial Doppler (TCD), perfusion CT (PCT), and neurologic examination during treatment course and follow-up. RESULTS: No angiographic effect was observed in 8 patients. The pooled PCT values revealed a reduction of time to peak ( P = .03) and mean transit time ( P = .17) 1 day after intervention. This effect did not persist during the following days. The pooled TCD analysis demonstrated a transient increase in flow 1 day after intervention ( P = .03). No trend was evident during the next 7 days after intervention. Additional infarction was experienced by 61.1% of patients. CONCLUSIONS: IAN in a selective patient group resulted in a positive response with reduction of angiographic vasospasm and increase in cerebral perfusion as detected by PCT after 24 hours. Therefore, IAN appears more effective than intra-arterial papaverine. Nevertheless the efficacy of IAN is temporary. Therefore, the search for more effective treatment strategies to reduce critical vasospasm and to improve cerebral perfusion must be continued.

Object The treatment of complex cerebrovascular or skull base pathological conditions necessitates a microsurgical blood flow preservation or augmentative revascularization procedure as either an adjunctive safety measure or a definitive treatment. The brain is susceptible to ischemia, and procedure-related risks can be minimized by the reduction of occlusion time or the use of a nonocclusive technique. The authors therefore analyzed the feasibility of an automatic device (C-Port xA, Cardica) designed for constructing an end-to-side anastomosis with or without flow interruption for a middle cerebral artery (MCA) bypass in a human cadaveric model and in an in vivo craniotomy simulation model. Methods Four Thiel-fixated human head specimens were prepared using 8 standard pterional craniotomies. The sylvian fissure was opened to access the anterior circulation and in particular the MCA. The length of the individual vessel segments was measured. The C-Port xA was tested on each of the 8 exposures. In addition the C-Port xA was deployed in an in vivo craniotomy simulator model in 10 New Zealand rabbits (a total of 20 anastomoses) by using the abdominal aorta jump graft model. Results Short-term patency was assessed by angiography and histological findings. In all 8 sylvian exposures, construction of an MCA anastomosis with the aid of the C-Port xA was feasible. All 20 jump graft anastomoses performed in the in vivo craniotomy simulator were found to be patent. Conclusions The anatomical studies as well as the in vivo craniotomy simulation studies demonstrated that the dimensions of the automated end-to-side anastomosis device are suitable for an extracranial–intracranial high-flow bypass on the MCA. Further miniaturization and special adaptation of this device would allow bypass procedures to more proximal intracranial vessels.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. EG-1962 is a sustained release formulation of nimodipine for intraventricular delivery into the subarachnoid space while avoiding dose-limiting hypotension common with systemic administration. We conducted a phase 1/2a multicenter, controlled, randomized, open label, dose escalation study to determine the maximum tolerated dose (MTD) and assess safety, tolerability, pharmacokinetics and clinical outcome at 90 days on the extended Glasgow outcome scale (GOSE) of a single intraventricular dose of EG-1962 (www.clinicaltrials.gov Identifier: NCT01893190). Subjects with aSAH repaired by clipping or coiling were randomized within 60 hours of aSAH to EG-1962 or oral nimodipine if they were World Federation of Neurological Surgeons grade 2 to 4 and had a ventricular catheter. Cohorts of 12 subjects received 100, 200, 400, 600, 800 or 1200 mg EG-1962 (9 per cohort) or oral nimodipine (3 per cohort). The MTD was 800 mg EG-1962. Plasma nimodipine concentrations after administration of EG-1962 were sustained for 21 days and increased in a dose-dependent fashion. Cerebrospinal fluid nimodipine concentrations with EG-1962 were orders of magnitude higher than in plasma and with oral nimodipine. There was one serious adverse event (possible allergic reaction) related to EG-1962 (400 mg) and two EG-1962 dose limiting toxicities (increased intracranial pressure, 400 and 800 mg); all were without clinical sequelae. There was no EG-1962-related hypotension as compared to hypotension in 17% (3/18) with oral nimodipine. Favorable outcome (GOSE 6-8) was achieved in 27 of 45 (60%) EG-1962 subjects (5 of 9 with 100, 6 of 9 with 200, 7 of 9 with 400, 4 of 9 with 600 and 5 of 9 with 800 mg) and 5 of 18 (28%) oral nimodipine subjects. Improved efficacy was supported by reduction in delayed cerebral ischemia (15/45 [33%] EG-1962 versus 11/18 [61%] oral nimodipine) and rescue therapy (11/45 [24%] versus 10/18 [56%]) in EG-1962 subjects. Intraventricular EG-1962 was safe and tolerable to 800 mg, associated with sustained and dose-dependent nimodipine plasma concentrations,improved clinical outcome and reduced delayed cerebral ischemia and use of rescue therapy after aSAH.

Da Li and co-workers present a detailed sub-analysis of their series of petroclival meningiomas, which is the largest monocentric series published to date [5, 6]. In the current work, they restrict the analysis to medium and large tumours of more than 2 cm in diameter—the tumours that really cause difficulties for microsurgery as well as stereotactic radiosurgery. Gross total resection was achieved in 56 % of patients; dysfunctions of the cranial nerves were the most common complication and occurred in two-thirds of the patients. Immediately following surgery, morbidity temporarily increased and the Karnovsky Performance Scale temporarily decreased on average. The case fatality rate amounted to 2 %. Permanent surgical morbidity remained in 20 % of patients during the average long-term follow-up of almost 10 years, but significantly more patients lived independently after than before surgery (61 vs 46 %). One-fourth of patients were lost to longterm follow-up, so that the numbers regarding long-term outcome must be appreciated with sound judgment. These key data focusing on medium and large petroclival meningioma are important, although difficult to compare with the smaller unselected series [1, 3, 7–9, 12]. Petroclival meningiomas smaller than 2 cm carry a much smaller surgical risk than large tumours, and in unselected series the small tumours dilute information regarding the problematic larger tumours. Numbers for the rate of gross total resection and surgical morbidities given in the published unselected series differ widely: gross total resection between one-third and twothirds, and surgical morbidity also between one-third and twothirds. Stereotactic radiosurgery is an obvious alternative for primary treatment of these tumours. There are not very many reports—a fact that reflects concerns regarding tolerance in view of the vicinity of the brainstem. The Pittsburgh group reported their experience in a series of 39 patients with a median follow-up period of 37 months. Neurological status improved in 21 %, remained stable in 66 %, and eventually worsened in 13 %. Tumour volumes decreased in 23 %, remained stable in 68 % and increased in 8 % [13]. It appears that there is some kind of consensus that radiosurgery is an adjuvant modality for larger petroclival meningiomas, which cannot be recommended as first-line therapy. However, there is little doubt that in analogy to vestibular schwannomas, stereotactic radiosurgery has evolved to an alternative for smallsized meningiomas. The substantial proportion of incomplete removal in most series and the significant rate of morbidity suggest that petroclival meningiomas remain not only difficult but basically problematic for microsurgery. Finding the balance between radicality and risk is the real challenge of managing petroclival meningiomas. The surgical risk appears to be influenced by (1) tumour size, (2) consistency and texture of the tumour and (3) the interface between tumour and arteries, brainstem and cranial nerves. In my opinion, it is hardly possible to dissect an adherent or even encased pontine artery from the tumour. Better presurgical imaging should provide more information with regard to tumour consistency and interface to vital structures. The techniques to define mechanical properties are partially already available, but they must be integrated into clinical routine [10, 11, 15]. The techniques to define interfaces are also available with the heavily contrasted T2* Hans-Jakob Steiger steiger@uni-duesseldorf.de

Estimation of the natural history of arteriovenous malformations based on short-term observation is potentially biased by multiple factors. Retrieval of demographic information of all AVM patients of national data pools and comparison with the national demographic profile might be another way to approach the natural history. Upon request, the German Federal Statistical Office provided the numbers of patients admitted in Germany from 2009 through 2013 with ICD Q28.2 (brain AVM) as primary discharge diagnosis, and the corresponding age distribution. Age-related admission rates of AVM were calculated by comparison with the German demographic distribution. A total of 6527 patients were hospitalized from 2009-2013 with brain AVM (Q28.2) as the principal diagnosis. Age-specific admission rate during the first year of life was high with 19.0/100,000 during the 5-year study period, corresponding to a yearly admission rate of 3.8 per 100,000 babies. Apart from the high admission rate during the first year of life, the admission rate was low, but steadily increasing during first decades of life reaching a plateau with 11.1/100,000 in the age group 30-34 years, corresponding to an annual admission rate of 2.2/100,000. After the age of 30-34 years, admission rates decreased continuously, reaching 0 in the age group 90-95 years. The lifetime risk of admission in terms of admission per 100,000 age-matched people was calculated by retrograde integration of the admission rates. At the age of 1 year, the cumulative number of future admissions for AVM during lifetime amounted to 131.3/100,000 children. For the older age groups, the chance of future admission for AVM decreased as expected, reaching 43.8/100,000 by the age of 50 and 0 by the age of 90. Despite some open issues, the current data suggests that achieving old age with an untreated brain AVM is unlikely. Furthermore, the data support the concept that most brain AVMs are not necessarily a congenital entity but develop during the first decades of life.

The aim of our study was to clarify the expression and gene copy number levels of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D), which is thought to be a regulator of the p53 protein in meningiomas of all three different WHO grades. Genomic DNA and mRNA were extracted from frozen tissues of meningiomas (WHO grade I, 20 cases; grade II, 17 cases; grade III, 20 cases). For analysis of the mRNA expression and gene dosage level of PPM1D, semiquantitative duplex RT-PCR, real-time RT-PCR, and semiquantitative duplex PCR were performed. We also analyzed several genes which locate near PPM1D in the genomic locus 17q22-24 using semiquantitative duplex RT-PCR. We found that the mean mRNA expression of PPM1D is higher in WHO grade II and III meningiomas than in grade I tumors. This finding is accompanied by moderate gene dosage increases for PPM1D in meningiomas of higher grades. Other genes located in the vicinity of PPM1D also showed mRNA overexpression in single meningioma cases. For these genes, however, no significant expression differences between meningioma grades could be observed. Thus, PPM1D in the chromosomal location 17q22-24 might be the most relevant candidate gene with respect to a potential functional implication in meningioma progression.

We appreciate the comments by Bervini and Morgan regarding our publication BMicrosurgical resection of Spetzler–Martin grades 1 and 2 unruptured brain arteriovenous malformations results in lower long-term morbidity and loss of quality-adjusted life-years (QALY) than conservative managementResults of a single group series^. They challenge our somewhat-simplified conclusion that at present a benefit of microsurgical treatment of Spetzler–Martin (SM) grade 1 and 2 arteriovenous malformation (AVMs) can be accepted with certainty while this is not the case for SM grades 3 and 4. They argue that, despite its high morbidity, microsurgical treatment mortality for unruptured SM grade 3 AVM is likely lower than the long-term mortality resulting from the natural history. In general, it is somewhat difficult to compare a onetime risk (i.e., treatment-related morbidity) with a longterm risk (natural history of AVMs) as these are two different quantities: Is it better for a 40-year-old patient to live with a permanent neurological deficit without the threat of hemorrhage and premature death, or to live and work normally up to the age of 50 or 60 and then possibly suffer a hemorrhage and die suddenly? We tried to partially solve this dilemma by normalizing morbidity and mortality in terms of lost qualityadjusted life-years (QALY). Although with this approach SM grade 3 as a whole group did not benefit from microsurgery, patients younger than 39 years did. A clear benefit of surgical treatment was seen in the younger patients with SM grade 3 AVMs. The surgical risk in these patients with respect to lost QALY was negated by the natural course within 5–7 years. However, statistical uncertainty due to the small sample size precluded us from drawing more definitive conclusions regarding the potential benefit of microsurgical resection in younger patients with SM grade 3 AVM. Thus, we agree that the appropriate management of AVM patients requires careful and nuanced assessment of risks and benefits of both invasive and conservative treatment for every patient individually until more data in this respect become available. * Hans-Jakob Steiger steiger@uni-duesseldorf.de

Objective Different surgical options are available to treat radicular pain syndromes of the cervical spine. Use of the posterior approach for foraminotomy and sequestrectomy (Frykholm) fusion can be avoided, but neck pain affects the postoperative course. This retrospective study compares the classical Frykholm approach and the transtubular microsurgical approach for foraminotomy. Methods From 2004 to 2012, 40 patients fulfilled the inclusion criteria and were enrolled into this retrospective study. The classical Frykholm approach was performed on 25 affected levels. The transtubular microsurgical approach was used on 19 affected levels. Endpoints were neck pain, radicular pain, surgery time, duration of hospital stay, and long-term outcomes. Results For the transtubular microsurgical approach and the classical Frykholm approach, the mean surgery time was 77.65 ± 23 minutes and 104 ± 27.59 minutes ( P = 0.003), respectively. Radicular pain improved in all patients regardless of the technical approach. Significant differences were observed in neck pain on the first postoperative day ( P = 0.003) and at discharge ( P = 0.006), resulting in a shorter hospital stay of 4.82 days ± 2.1 for the transtubular microsurgical approach in comparison with 7.43 days ± 3.2 for the Frykholm approach ( P = 0.005). According to the criteria of Odom, the rate of an excellent or good outcome was 97.5% (67.5% excellent and 30% good), without any differences between the compared approaches. Conclusion The transtubular microsurgical approach shows advantages regarding postoperative neck pain, surgery time, and hospital stay with a trend towards an earlier return to work.

Although the benefit of intervention for unruptured arteriovenous malformation (AVM) with regard to stroke rates and long-term disability remains unclear, most patients present with symptoms, such as epilepsy, headache, or neurological deficits, compromising their quality of life. Detailed analysis of the long-term effects of microsurgical treatment on quality of life, epilepsy, and headache was the purpose of this audit. A series of 25 microsurgically treated patients were interviewed on average 7 ± 5 years after treatment. Detailed information was obtained regarding frequency and severity of seizures and headaches. Outcome data was compared with the initial complaints and neurological findings. The Short Form (SF)-36 was used to assess health-related quality of life. On average, the SF-36 scores did not differ significantly from the age-matched German norm values. Patients suffering from chronic headache prior to treatment scored worse in most SF-36 subscales than patients without headache at the time of treatment, and the difference was significant in the SF-36 dimensions physical role functioning and emotional role functioning (P = 0.04). In contrast, there was a trend for patients treated for incidental AVM to score somewhat better than the age norm. Twelve patients had been admitted with epilepsy. At the time of follow-up, all patients were seizure free (Engel class I), although 7 of them continued to take antiepileptic medication. Two of 13 patients without epilepsy at the time of treatment experienced seizures sometime during the post treatment course and were under medication at the time of long-term follow-up interview. At the time of the audit, 7 of 11 patients admitted with chronic headache necessitating regular use of pain medication indicated not to use pain medication any longer. Our data suggest that initial symptoms leading to diagnosis and treatment of unruptured AVM may influence long-term quality of life following treatment. Patients admitted with headache as the chief complaint appear to fare worse than patients with epileptogenic or incidental AVMs.

Objective With the publication of the European Organization for Research and Treatment of Cancer/National Cancer Information Center (EORTC/NCIC) trial, concomitant radiochemotherapy followed by intermittent chemotherapy became the new treatment standard for patients with primary glioblastoma. Eight years after widespread introduction of this protocol, it is of interest to investigate whether this new standard has been established in daily neuro-oncologic practice. We were particularly interested in its practicality within a neurosurgical neuro-oncologic setting. Patients and Methods We analyzed primary glioblastoma patients diagnosed between 2005 and 2013 treated at our center according to the EORTC/NCIC trial. Parameters associated with treatment performance (interruption of radiotherapy, concomitant chemotherapy and intermittent chemotherapy, total number of cycles, and side effects) were retrospectively analyzed and compared with the available data from the EORTC/NCIC trial. Results In this single-center retrospective study, we identified 189 patients (116 men, 73 women; median age: 62 years) who were treated according to the EORTC/NCIC trial protocol. A total of 176 patients received cytoreductive surgery; 13 patients had stereotactic biopsy only (EORTC/NCIC trial: 239 patients and 48 patients, respectively). Radiotherapy had to be interrupted in 9 patients (5%) (EORTC/NCIC trial: 15 patients [5%]) and concomitant chemotherapy in 26 patients (14%) (EORTC/NCIC trial: 37 patients [13%]). In 156 patients (83%), adjuvant TMZ chemotherapy was initiated (6 median temozolomide [TMZ] cycles; range: 1–30). In the EORTC/NCIC trial, 223 patients (47%) received the intermittent chemotherapy protocol (median: 3 cycles; range: 1–7). Overall, 97 patients (62%) completed 6 TMZ cycles (EORTC/NCIC-trial: 105 patients [47%]); dose escalation to 200 mg/qm at the second cycle was performed in 91 patients (58%) (versus 149 patients [67%]). Intermittent TMZ therapy was discontinued in 59 patients (38%) (versus 118 patients [53%]). Median overall survival in our patient cohort was 19 months (versus 14.6 months); median time to progression was 9 months (versus 6.9 months). Conclusion Comparison between the feasibility of the treatment protocol established by the EORTC/NCIC trial (performed within the setting of a prospective randomized trial) and the daily routine in a dedicated neurosurgical neuro-oncologic department demonstrates that the protocol is suitable for daily practice within a neurosurgical unit.