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Background Catheter-based lysis with recombinant tissue plasminogen activator (rtPA) is a well-established therapy for spontaneous intracerebral hemorrhage (ICH). The effectiveness of this therapy can be increased with ultrasound, but the optimal conditions are not yet clearly established. Using a novel in vitro system of blood clots previously developed by our group, we investigated various parameters of intralesional sonothrombolysis using an endosonography catheter in combination with rtPA. Methods Standardized human blood clots were equipped with a drainage catheter and weighed before and after 4 treatments: control (drainage only), rtPA only, ultrasound only and the combination of rtPA+ultrasound. The effectiveness of ultrasound was further analysed in terms of optimal frequency, duration and distance to the probe. Temperature and acoustic peak rarefaction pressure (APRP) were assessed to analyse potential adverse effects and quantify lysis. Histo-morphological analysis of the treated clots was performed by H&E staining and confocal laser scanning microscopy using fluorescent fibrinogen. Results The combined treatment rtPA+ultrasound achieved the highest lysis rates with a relative weight of 30.3%±5.5% (p≤0.0001) compared to all other groups. Similar results were observed when treating aged clots. Confocal fluorescent microscopy of the treated clots revealed a rarefied fibrin mesh without cavitations. No relevant temperature increase occurred (0.53±0.75°C). The optimal insonation treatment time was 1 hour. APRP measurements showed a lysis threshold of 515.5±113.4 kPa. Application of 10 MHz achieved optimal lysis and lysis radius, while simultaneously proving to be the best frequency for morphologic imaging of the clot and surrounding tissue. Conclusions These promising data provide the basis for an individualized minimal invasive ICH therapy by rtPA and sonothrombolysis independent of ICH age.

Background Trigeminal neuralgia (TN) represents one of the most disabling pain syndromes. Several diseases have been described as etiological triggers of TN, vascular compression of the trigeminal nerve being the most frequent cause. Here, we describe for the first time a rare case of TN caused by an infiltration of an isolated Epstein-Barr virus (EBV) B-cell lymphomatoid granulomatosis (LYG) mass into the Meckel's cave and cavernous sinus. Case description A 51-year-old woman undergoing immunosuppressant treatment for Crohn's disease presented due to right-sided TN. Magnetic resonance imaging (MRI) scans revealed an isolated lesion affecting the right Meckel's cave and lateral wall of the cavernous sinus. We accomplished tumor resection through a subtemporal extradural approach and the patient recovered successfully from surgery. Histological examination revealed an LYG, and a blood test confirmed low but positive EBV counts. The immunosuppressant therapy was discontinued and we assumed a watchful waiting management. During a 41-months' follow-up there was neither evidence of LYG recurrence nor an increase of EBV counts. Conclusions LYG, an angiodestructive disease associated with EBV reactivation in the context of immune dysfunction and often associated with an aggressive behavior or even malignant transformation, should be considered as a rare differential diagnosis of TN associated with skull base lesions. The management of this rare disease is still controversial and varies from limiting the treatment to correcting immune dysfunction up to chemotherapy. In this case of an isolated mass, surgical excision and discontinuation of immunosuppressants were effective to prevent the relapse of the disease in a long-term follow-up.

BackgroundTranscranial Doppler (TCD) was shown to enhance intravascular fibrinolysis by rtPA in ischemic stroke. Studies revealed that catheter-based administration of rtPA induces lysis of intracerebral hemorrhages (ICH). However, it is unknown whether TCD would be suitable to enhance rtPA-induced fibrinolysis in patients with ICH. The aim of this study was to assess the potential of TCD to enhance rtPA-induced fibrinolysis in an in vitro clot system.MethodsReproducible human blood clots of 25 ml were incubated in a water bath at 37°C during treatments. They were weighed before and after 6 different treatments: (I) control (incubation only), (II) rtPA only, (III) one Doppler probe, (IV) two Doppler probes placed vis-à-vis, (V) one probe and rtPA and (VI) two probes and rtPA. To quantify lysis of the blood clots and attenuation of the Doppler through a temporal squama acoustic peak rarefaction pressure (APRP) was measured in the field of the probes. Temperature was assessed to evaluate possible side effects.ResultsClot weight was reduced in all groups. The control group had the highest relative end weight of 70.2%±7.2% compared to all other groups (pConclusionsTCD significantly enhances rtPA-induced lysis of blood clots, and the effect is amplified by using multiple probes. Our results indicate that bitemporal TCD insonation of hematomas could be a new and safe approach to enhance fibrinolysis of ICH´s treated with intralesional catheter and rtPA.

Glioblastoma inevitably recurs despite aggressive therapy. Therefore, it would be helpful to predict the location of tumor recurrence from postoperative imaging to customize further treatment. O-(2-Thirty-two consecutive patients with perioperative and follow-up imaging data available were included. On postoperative FET-PET, the tumor/normal brain (TTB) ratio around the resection cavity borders was measured. Increased TTB ratios were recorded and anatomically correlated with the site of later tumor recurrence. On postoperative magnetic resonance imaging (MRI), residual contrast-enhancing tumor correlated with the site of later tumor recurrence.Location of progression was predictable using MRI alone in 42% of patients by residual tumor on postoperative MRI. FET-PET was predictive in 25 patients by a clear hot spot at the site of later tumor recurrence. In 3 patients, it was partially predictive and in 4 was not predictive of the tumor recurrence location. One patient without any tracer uptake was recurrence free at the last follow-up examination. In contrast to the postoperative MRI results, tumor recurrence was found in 79% at a site of elevated TTB ratio on postoperative FET-PET. Therefore, the predictability of the tumor recurrence location using postoperative FET-PET was greater than that with MRI, and all cases predictable using MRI could have been predicted using FET-PET.Postoperative FET-PET can be helpful for planning subsequent therapy, such as repeat resection or radiotherapy, because tumor recurrence can be predicted with relatively greater sensitivity than with MRI alone.

Due to a metadata tagging error the names of Stephanie E. Combs and Jan S. Kirschke were indexed incorrectly. Stephanie E. is the author's given name, and Jan S. is the author's given name.

Background Montreal Cognitive Assessment (MoCA) represents a short screening tool for neuropsychological deficits. The study’s aim was to test feasibility and acceptance of MoCA in patients with brain tumours perioperatively. Methods Patients with supratentorial located brain tumours were assessed preoperatively (t1, day −1) and postoperatively (t2, day 3–5) using EORTC-QLQ-C30 + BN20, Distress Thermometer (DT) and the MoCA test (different versions). Feasibility was evaluated by a feedback form and patients were asked about perceived discomfort, overstraining or complexity of MoCA. Results of MoCA were correlated with clinical factors. Results 63 patients participated, 19 were male. Mean age was 56 years. Mean completion time of MoCA was 11 min (both t1 and t2). At t1, in 27% “moderate or major difficulties” occurred during MoCA assessment vs. 41% at t2. Most of the patients (t1, 93% vs. t2, 86%) negated to be overstrained by MoCA. Better “physical function” according to EORTC-QLQ-C30 (p = 0.041, Pearson = 0.321) and higher KPS (p = 0.012, Pearson = 0.578) correlated to higher MoCA scores. Higher distress at t2 was found to be correlated with a stronger deterioration of MoCA at t2 vs. t1 (p = 0.03, Spearman-Rho = .695). Conclusion The MoCA test was well accepted by the patients and implementable in clinical routine. Further investigations evaluating the sensitivity and specificity of the test in brain tumour patients are required.

Though cognitive function is proven to be an independent predictor of survival in patients with intrinsic brain tumors, cognitive functions are still rarely considered. Aim of this study was to assess neurocognitive function and to identify risk factors for neurocognitive deficits. 103 patients with primary neuroepithelial tumors who received tumor resections or biopsies were included in this prospective study. The following data was acquired: mini-mental state examination, preoperative tumor volume, WHO grade, tumor entity and location, and the Karnofsky performance status scale. Furthermore, patients participated in extensive neuropsychological testing of attentional, memory and executive functions. General factors like age, clinical status, WHO grade, tumor volume and tumor location correlated with patients' neurocognitive functions. Affection of the parietal lobe resulted in significant impairment of attention and memory functions. Frontal lobe involvement significantly affected patients' abilities in planning complex actions and novel problem solving. Patients with temporal lesions were more likely to have impaired memory and executive functions. Comparing results among neuroepithelial tumor patients enables the identification of risk factors for cognitive impairment. General parameters such as age, KPS score, tumor size, and WHO grade are apart from the respective tumor location of high importance for neurocognitive function.

BACKGROUND: The GLARIUS trial, which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) compared with standard temozolomide in the first-line therapy of O(6)-methylguanine-DNA methyltransferase (MGMT)-nonmethylated glioblastoma, showed that progression-free survival was significantly prolonged by BEV/IRI, while overall survival was similar in both arms. The present report focuses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease. METHODS: Patients (n = 170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard temozolomide. At least every 3 months KPS was determined and QoL was measured using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life and 20-item Brain Neoplasm questionnaires. A generalized estimating equation (GEE) model evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration were analyzed separately. RESULTS: In all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions of motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation. CONCLUSIONS: GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM.

Background The knowledge of exact tumor margins is of importance for the treating neurosurgeon, radiotherapist, and oncologist alike. The aim of this study was to investigate whether tumor volume and tumor margins acquired by magnetic resonance imaging (MRI) are congruent with the findings acquired by O-(2-(18F)-fluoroethyl)- l -tyrosine–positron emission tomography (FET-PET). Methods Patients received FET-PET and MRI before surgery for brain metastases. Metastases were quantified by calculating tumor-to-background uptake ratios using FET uptake. PET and MRI-based tumor volumes, as well as areas of intersection, were assessed. Results Forty-one patients were enrolled in the study. The maximum tumor-to-background uptake ratio measured in all of our patients harboring histologically proven viable tumor tissue was >1.6. Absolute tumor volumes acquired by FET-PET and MRI were not congruent in our patient cohort, and tumors identified in FET-PET and MRI only partially overlapped. The ratio of intersection (intersection of tumor defined by MRI and tumor defined by FET-PET at the ratio of tumor defined by FET-PET) was within a range of 0.27–0.68 when applying the different thresholds. Conclusions Our study therefore indicates that treatment planning based on MRI or PET only might have a substantial risk of undertreatment at the tumor margins. These findings could have important implications for the planning of surgery as well as radiotherapy, although they have to be validated in further studies.

INTRODUCTION: Neurosurgical training aims at educating future generations of specialist neurosurgeons and at providing the highest-quality medical services to patients. Attaining and maintaining these highest standards constitutes a major responsibility of academic or other training medical centers. METHODS: An electronic survey was sent to European neurosurgical residents between 06/2014 and 03/2015. Multiple logistic regression analysis was used to assess the effect size of the relationship between responder-specific variables (e.g., age, gender, postgraduate year (PGY), country) and the outcomes (e.g., satisfaction). RESULTS: A total of 652 responses were collected, of which n = 532 were taken into consideration. Eighty-five percent were 26-35 years old, 76 % male, 62 % PGY 4 or higher, and 73.5 % working at a university clinic. Satisfaction rates with theoretical education such as clinical lectures (overall: 50.2 %), anatomical lectures (31.2 %), amongst others, differed largely between the EANS member countries. Likewise, satisfaction rates with practical aspects of training such as hands-on surgical experience (overall: 73.9 %), microsurgical training (52.5 %), simulator training (13.4 %), amongst others, were highly country-dependant. In general, 89.1 % of European residents carried out the first surgical procedure under supervision within the first year of training. Supervised lumbar-/cervical spine surgeries were performed by 78.2 and 17.9 % of European residents within 12 and 24 months of training, respectively, and 54.6 % of European residents operate a cranial case within the first 36 months of training. Logistic regression analysis identified countries where residents were much more or much less likely to operate as primary surgeons compared to the European average. The caseload of craniotomies per trainee (overall: 30.6 % ≥10 craniotomies/month) and spinal procedures (overall: 29.7 % ≥10 spinal surgeries/month) varied throughout the countries and was significantly associated with more advanced residency (craniotomy: OR 1.35, 95 % CI 1.18-1.53, p

Vertebral artery injury (VAI) during foraminal decompression in cervical spine surgery in the absence of repositioning or screw stabilization is rare. Without immediate recognition and treatment, it may have disastrous consequences. We aimed to describe the incidence and management of iatrogenic VAI in low-risk cervical spine surgery. The records of all patients who underwent surgical procedures of the cervical spine between January 2007 and May 2012 were retrospectively consecutively evaluated. Anterior cervical discectomy and fusion or arthroplasty as well as dorsal foraminal decompression through the Frykholm approach in degenerative diseases were defined as low-risk surgeries (n = 992). VAI occurred in 0.3 % (n = 3) of 992 procedures: in one case during a dorsal foraminal decompression, and in two cases during the anterior cervical discectomy and fusion (ACDF) of two or four levels, respectively. In the first case, the VAI was intraoperatively misdiagnosed. Despite an initially uneventful course, the patient suffered hemorrhage from a pseudoaneurysm of the injured VA 1 month after surgery. The aneurysm was successfully occluded by endovascular coiling. In both ACDF cases, angiography and endovascular stenting of the lacerated segment proceeded immediately after the surgery. All three patients suffered no permanent deterioration. In a high-volume surgical center, the incidence of VAI during low-risk cervical spine surgery is extremely low, comprising 0.3 % of all cases. The major risks are delayed sequels of the vessel wall laceration. In cases of VAI, immediate angiographic diagnostics and generous indications for endovascular treatment are obligatory.

OBJECT Resection of a motor eloquent lesion has become safer because of intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical motor evoked potentials (scMEPs) is increasingly used to optimize patient safety. So far, scMEP stimulation has been performed intermittently during resection of eloquently located lesions. Authors of the present study assessed the possibility of using a resection instrument for continuous stimulation of scMEPs. METHODS An ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a monopolar subcortical stimulation probe. The effect of the aspirator’s use at different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation intensity was examined in a saline bath. Afterward monopolar stimulation with the surgical aspirator was used during the resection of subcortical lesions in the vicinity of the corticospinal tract in 14 patients in comparison with scMEP stimulation via a standard stimulation electrode. During resection, the stimulation current at which an MEP response was still measurable with subcortical stimulation using the surgical aspirator was compared with the corresponding stimulation current needed using a standard monopolar subcortical stimulation probe at the same location. RESULTS The use of ultrasound at different energy levels did result in a slight but irrelevant increase in stimulation energy via the tip of the surgical aspirator in the saline bath. Stimulation of scMEPs using the surgical aspirator or monopolar probe was successful and almost identical in all patients. One patient developed a new permanent neurological deficit. Transient new postoperative paresis was observed in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14) cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14). CONCLUSIONS Continuous motor mapping using subcortical stimulation via a surgical aspirator, in comparison with the sequential use of a standard monopolar stimulation probe, is a feasible and safe method without any disadvantages. Compared with the standard probe, the aspirator offers continuous information on the distance to the corticospinal tract.

OBJECT Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. METHODS The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. RESULTS The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. CONCLUSIONS In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.

Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy. The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy. Overall, 209 patients undergoing surgery for newly diagnosed WHO grade IV gliomas were retrospectively analyzed, and pre- and postoperative tumor volumes were manually segmented (cm3). Survival analyses were performed, including prognostic factors such as age, Karnofsky performance score (KPS), O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, and adjuvant treatment regimen. Pre- and postoperative tumor volume is significantly associated with pre- and postoperative KPS, as well as age (p

Die operative Therapie von Rezidivgliomen stellt eine Strategie dar die zunehmend an Bedeutung gewinnt, obwohl EBM-Level-1- oder Level-2-Studien dafur bislang fehlen. Allerdings deuten Level-3-Studiendaten darauf hin, dass sich durch eine erneute operative Resektion von Rezidivgliomen ein onkologischer Vorteil ergibt. Dabei kommen technisch die gleichen Hilfsmittel wie bei einer Primarresektion zum Einsatz.

Background Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Particularly in the field of cardiac and vascular surgery, the application of a brief ischemic stimulus not only in the target organ but also in remote tissues can prevent subsequent ischemic damage. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences. Methods Sixty patients were randomly assigned to two groups, with 1:1 allocation, stratified by tumor type (glioma or metastasis) and previous treatment with radiotherapy. rIPC was induced by inflating a blood pressure cuff placed on the upper arm three times for 5 min at 200 mmHg in the treatment group after induction of anesthesia. Between the cycles, the blood pressure cuff was released to allow reperfusion. In the control group no preconditioning was performed. Early postoperative magnetic resonance images (within 72 h after surgery) were evaluated by a neuroradiologist blinded to randomization for the presence of ischemia and its volume. Results Fifty-eight of the 60 patients were assessed for occurrence of postoperative ischemia. Of these 58 patients, 44 had new postoperative ischemic lesions. The incidence of new postoperative ischemic lesions was significantly higher in the control group (27/31) than in the rIPC group (17/27) (p = 0.03). The median infarct volume was 0.36 cm3 (interquartile range (IR): 0.0–2.35) in the rIPC group compared with 1.30 cm3 (IR: 0.29–3.66) in the control group (p = 0.09). Conclusions Application of rIPC was associated with reduced incidence of postoperative ischemic tissue damage in patients undergoing elective brain tumor surgery. This is the first study indicating a benefit of rIPC in brain tumor surgery. Trial registration German Clinical Trials Register, DRKS00010409 . Retrospectively registered on 13 October 2016.

Treatment of glioblastoma(GB) patients amenable only for a subtotal resection(STR) is controversial. Since outcome of patients is affected by surgical management, our aim was to assess surgical decision making and resulting outcome in patients with highly eloquent GBs.We retrospectively assessed GB patients with intended sub-total resection (STR) or stereotactic biopsy (STX) of 3 neurooncological centers operated between 2008 and 2013. A volumetric assessment of overall extent of resection(oEoR), presence of complications, new permanent neurological deficits(nPNDs) was performed. A central reviewer reassessed all cases blinded and gave recommendation on surgical management and on a potential EoR(pEoR) based on imaging data. We compared outcome data using Mann-Whitney-U-test and Sign-Rank-Test. Survival was assessed based on Kaplan-Meier-estimates.97 patients were included. In 17 patients received STX, 70 patients a STR and 10 patients a near total resection (NTR, EoR95%). Median OS was significantly different from STX patients only if NTR was reached (16 vs. 7 months, p=0.042). The central reviewer recommended a more aggressive strategy(NTR or STR resp.) in 41 patients and a less aggressive strategy in 13 patients. Overall, management recommendation was significantly different to clinical treatment (p0.001). Mean pEoR was significantly higher than oEoR (85.7% vs. 71.3%, p=0.001). Regarding the different OR subgroups, no significant differences were found in the NTR group(12/13 ties, p=1) and in STX group (14/17 ties, p=0.125). In STR group, a significant difference was found (p=0.001). In 38/69 patients a NTR and in 13/77 patients a STX was recommended.Surgery in GB patients with intended STR requires precise preoperative planning since potential EoR is mainly underestimated. Especially, patients with lesions amenable for a NTR should not be missed.

Electronic survey.The aim of this study was to identify the international nuances in surgical treatment patterns for severals lumbar degenerative conditions, specifically, to identify differences in responses in each country groupand different treatment trends across countries.Significant variations in treatment of lumbar degenerative conditions exist among spine surgeons, related to the lack of established consensus in the literature.An online survey with preformulated answers was submitted to 52 orthopedic surgeons, 50 neurosurgeons from four different countries (United States, France, Spain, and Germany) regarding five vignette-cases. Cases included: multilevel stenosis, monolevel stenosis, lytic spondylolisthesis, isthmic lysis, and degenerative scoliosis. The variability for each country was calculated according to the Index of Qualitative Variation (IQV = 0: no variability and 1: maximal variability). We used Fleiss kappa (range: from -1, poor agreement, to 1, almost perfect agreement) for assessing the reliability of agreement between the participants concerning specialties, countries, and age groups.For the two stenosis cases, US surgeons were more likely to propose decompression (IQV multilevel = 0.47 and monolevel = 0.32) comparing with European countries more heterogeneous (all IQV0.70) and more frequently proposing fusion. As regards degenerative scoliosis, all attitudes were extremely heterogeneous with IQV0.8. Fusion for isthmic spondylolisthesis was more consensual (all IQV0.63), but attitudes were more heterogeneous for isthmic lysis (IQV ranged from 0.48 to 0.76) with anterior approach proposed in France (37%) and United States (19.2%).The overall interrater agreement was equally slight not only for neurosurgeons (Fleiss Kappa = 0.04) and orthopedic surgeons (Kappa = 0.13), but also for countries (Kappa0.13) and age groups (Kappa0.1).In this study, we found substantial agreement for some spinal conditions but a high variability in some others: intranational and international variations were observed, reflecting the lack of literature consensus.2.

Background RNAs within extracellular vesicles (EVs) have potential as diagnostic biomarkers for patients with cancer and are identified in a variety of biofluids. Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF). Here we describe a multi-institutional study of RNA extracted from CSF-derived EVs of GBM patients to detect the presence of tumor-associated amplifications and mutations in epidermal growth factor receptor (EGFR). Methods CSF and matching tumor tissue were obtained from patients undergoing resection of GBMs. We determined wild-type (wt)EGFR DNA copy number amplification, as well as wtEGFR and EGFR variant (v)III RNA expression in tumor samples. We also characterized wtEGFR and EGFRvIII RNA expression in CSF-derived EVs. Results EGFRvIII-positive tumors had significantly greater wtEGFR DNA amplification (P = 0.02) and RNA expression (P = 0.03), and EGFRvIII-positive CSF-derived EVs had significantly more wtEGFR RNA expression (P = 0.004). EGFRvIII was detected in CSF-derived EVs for 14 of the 23 EGFRvIII tissue-positive GBM patients. Conversely, only one of the 48 EGFRvIII tissue-negative patients had the EGFRvIII mutation detected in their CSF-derived EVs. These results yield a sensitivity of 61% and a specificity of 98% for the utility of CSF-derived EVs to detect an EGFRvIII-positive GBM. Conclusion Our results demonstrate CSF-derived EVs contain RNA signatures reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR expression and EGFRvIII status. The high specificity of the CSF-derived EV diagnostic test gives us an accurate determination of positive EGFRvIII tumor status and is essentially a less invasive "liquid biopsy" that might direct mutation-specific therapies for GBMs.

Objective: To optimize the assessment of received and requested psychosocial support by glioma patients in clinical practice and to assess distress and needs for support of patients’ caregivers. We provide results of the application of a “patients’ perspective questionnaire” (PPQ) applied for the first-time in glioma patients and first results of a caregiver survey. Methods: Patients harboring a glioma were assessed consecutively within their outpatient visits using the Distress Thermometer (DT, score ≥6 indicates significant burden), the EORTC-QLQ-C30+BN20 and the self-administered PPQ: First 9 items assess psychosocial distress by 5 step Likert-scales and respective support requested by patients. Next 10 items survey provided support and its subjective benefit for the individual patient. Last 7 items record support requested currently by patients (e.g. caregiver, physician etc.). In a subgroup, patients’ caregivers were assessed simultaneously by another questionnaire for caregivers developed for the study evaluating, inter alia, quality of life, distress and wish for support. Results: We prospectively enrolled 232 patients. 82% suffered from high-grade gliomas. Mean age was 52 years (range 20–87 yrs.). M:f ratio was1.25:1. Based on PPQ, we observed that 38% (87) of patients felt depressed, 44% (103) were anxious and 39% (91) tense/nervous. According to the results of PPQ, patients with DT ≥6 were significantly more often depressed, anxious and burdened due to the disease (p

Purpose To analyze if fractional anisotropy (FA) in nonenhancing peritumoral regions (NEPTRs) at baseline is associated with later tumor recurrence in glioblastoma. Materials and Methods Ethical approval was obtained for this retrospective, HIPAA-compliant study. FA was measured in 70 patients with glioblastoma in five regions of interest (ROIs) per patient in the NEPTR at preoperative magnetic resonance (MR) imaging with (166 regions) or without (184 regions) local contrast-enhancing tumor recurrence at follow-up MR imaging (median, 7.3 months; range, 0.9-46.6 months). ROIs were classified according to their location (white matter, cortex, fiber tracts, basal ganglia). Ratio of FA in the ROI of the NEPTR to that in the contralateral side (FAcontra) and to that in the internal capsule (FAint) was calculated. A generalized linear mixed model was performed. Ten-fold cross-validation was used for the receiver operating characteristics (ROC) analysis. Results FAcontra and FAint were significantly lower in regions with later tumor recurrence than in regions without (median FAcontra: 0.29 [interquartile range {IR}, 0.22-0.36] vs 0.46 [IR, 0.38-0.57]; median FAint: 0.20 [IR, 0.16-0.24] vs 0.29 [IR, 0.22-0.36], respectively). ROC analysis revealed an area under the ROC curve of 0.893 for FAcontra and of 0.815 for FAint, resulting in respective sensitivity and specificity of 85.5% and 84.2% for FAcontra and 86.7% and 66.8% for FAint. Conclusion Local tumor recurrence in the NEPTR may be predicted by FA metrics at baseline in patients with glioblastoma. This might be important for surgery or radiation planning. © RSNA, 2016 Online supplemental material is available for this article.

Background Multisegmental cervical instrumentations ending at the cervicothoracic junction may lead to significant adjacent segment degeneration. The purpose of this study was to compare the extent of sequential pathologies in the lower adjacent segment between patient groups with a primarily cervical instrumentation ending at C7 versus an instrumentation including the cervicothoracic junction ending at T1 or T2. Methods A retrospective analysis of 98 consecutive patients with multisegmental posterior cervical fusion surgery ending either at C7 or at T1 or T2 was performed. Radiographic parameters of degeneration at the adjacent segment below the instrumentation were determined postoperatively and at follow-up (FU), and the need for secondary interventions was documented. Results A total of 74 patients had a FU of at least 6 months (C7: n = 58, age 63 ± 11 years, FU 36 ± 26 months; T1/T2: n = 16, age 65 ± 13 years, FU 37 ± 21 months). There were no significant differences between the C7 and T1/T2 groups with regard to the change in kyphosis angle ( P = 0.162), disc height ( P = 0.204), or disc degeneration according to the Mimura grading system ( P = 0.718). Secondary interventions due to adjacent segmental pathology or implant failure were necessary in 18 of 58 (31%) of the C7 cases and in 1 of 16 (6.3%) of the T1/T2 cases ( P = 0.038). Conclusions Patients with multisegmental posterior cervical fusions ending at C7 showed a greater rate of clinically symptomatic pathologies at the adjacent level below the instrumentation. On the basis of our data and with its limitations in mind, one may consider to bridge the cervicothoracic junction and to end the instrumentation at T1 or T2 in those cases.

Resecting language-eloquent brain lesions is a major challenge in neurosurgery since we need to weight the risks of worsening the patients’ functional integrity and achieving a maximum safe resection. Although relevant functional brain structures can be identified intraoperatively by direct cortical mapping during awake surgery, a preoperative identification of functional anatomy is recommended in order to gauge surgical risks, evaluate resectability, plan the surgical approach, and identify potential starting points for intraoperative stimulation mapping.

Background context Although the incidence of pyogenic spinal infections is increasing, the ideal treatment of spondylodiscitis is still a controversially discussed issue. Furthermore, the proportion of multiresistant bacteria in spondylodiscitis is increasing, and treatment recommendations or reported results are missing for this especially difficult subset of patients. Purpose The aim of this study is to evaluate the surgical outcome and the postoperative antibacterial treatment regime. Study design Retrospective case series. Patient sample Patients treated for a spondylodiscitis from multiresistant bacteria at our department between 2006 and 2011. Methods Data were gathered through review of patients' case notes, relevant imaging, and electronic records. Magnetic resonance imaging of the whole spine including gadolinium (Gd)-enhanced T1 sequences and computed tomography scans of the affected regions were obtained in all cases. Outcome measures C-reactive protein (CRP) and complete blood cell count were analyzed in all cases using routine laboratory techniques. Neurologic deficits were classified according to the American Spinal Injury Association (ASIA) impairment scale. Results Twenty-five patients were identified (15 gram-positive and 10 gram-negative drug-multiresistant bacteria). The mean age at presentation was 66 years, and 14 patients were male (56%). All patients presented with pain, and a neurologic deficit was present in 11 (44%) cases. An epidural abscess was found in 11 (44%) cases. At admission, CRP was elevated in all cases with a mean of 13±9.2 mg/dL. The main source of infection was previous spine surgery (36%). All patients in this series underwent surgical debridement of the infection and instrumentation of the spine. Postoperative intravenous antibiotics were administered for 19±8.6 days followed by 3±0.3 months of oral antibiotic therapy. Eradication of the infection was achieved ultimately in all surviving patients. Out of 11 patients with neurologic deficits, 4 had a full recovery, 4 improved incompletely, and 3 remained unchanged after surgery. Conclusions Staged surgical immobilization and instrumentation and optimal debridement at the interdiscal space and spinal canal is a reliable approach to achieve complete healing of spinal infection with multiresistant bacteria. A period of intravenous antibiotic therapy of 2 to 3 weeks followed by a 3-month oral antibiotic therapy seems appropriate for most cases.

The MR image quality after intracranial aneurysm clipping is often impaired because of artifacts induced by metal implants. The purpose of the present study was to evaluate the benefit of a new WARP sequence with slice-encoding metal artifact correction (SEMAC) and view-angle tilting (VAT) MR imaging as novel artifact reduction techniques. A new WARP TSE (a work-in-progress software package provided by Siemens Healthcare) sequence was implemented for cranial applications based on a turbo spin echo (TSE) sequence. T1- and T2-weighted images with standard and WARP TSE sequences were acquired from 6 patients with 11 clipping sites, and the images were compared based on artifact size and general image quality. T2- and T1-weighted WARP TSE sequences resulted in a highly significant reduction of metal artifacts compared with standard sequences (T2w- WARP TSE: 89.8 ± 1.4 %; T1w- WARP TSE: 84.9 ± 2.9 %; p

BACKGROUND AND PURPOSE: Inter- and intratumor heterogeneity and the variable course of disease in patients with glioma motivate the investigation of new prognostic factors to optimize individual treatment. Here we explore the usefulness of standard static and more sophisticated dynamic 18 F-fluoroethyltyrosine-PET imaging for the assessment of patient prognosis. MATERIALS AND METHODS: Thirty-four consecutive patients with untreated, first-diagnosed, histologically proved glioma were included in this retrospective study. All patients underwent dynamic PET scans before surgery (± standard treatment) and were followed up clinically and by MR imaging. Static and dynamic tumor-to-background ratio, TTP, and slope-to-peak were obtained and correlated with progression-free survival. RESULTS: Twenty of 34 patients experienced progression, with a median progression-free survival of 28.0 ± 11.1 months. Dynamic TTP was highly prognostic for recurrent disease, showing a strong correlation with progression-free survival (hazard ratio, 6.050; 95% CI, 2.11–17.37; P P = .044), but not when using established static imaging parameters, such as maximum tumor-to-background ratio and mean tumor-to-background ratio. In the high-grade glioma subgroup, both dynamic and static parameters correlated with progression-free survival. The best results were achieved by defining ROIs around “hot spots” in earlier timeframes, underlining the concept of intratumor heterogeneity. CONCLUSIONS: 18 F-fluoroethyltyrosine-PET can predict recurrence in patients with glioma, with dynamic analysis showing advantages over static imaging, especially in the low-grade subgroup.

A prospective randomized study.To compare occupational radiation exposure to the surgeon, as well as the patient, during posterior lumbar spine instrumentation in 10 navigated cases (navigated) versus 11 cases using the freehand technique (non-navigated).The use of navigation increases the accuracy of posterior lumbar instrumentation.A further speculated benefit of navigation is the reduction of radiation exposure of the surgeon. However, this has so far not been evaluated in such comparative manner.Radiation exposure to the surgeon was measured by digital dosimeters placed at the level of the eye, chest, and dominant forearm. Radiation exposure was measured from the time of positioning of the patient to the end of the procedure both for navigated (intraoperative 3-dimensional [3D] fluoroscopy-based) and non-navigated (2-dimensional fluoroscopy-guided) freehand posterior lumbar spine instrumentations. A 3D fluoroscopic scan was routinely performed at the end of the procedure for all patients.Patients were distributed evenly in the 2 groups in terms of sex, age, body mass index, and the number of operated levels. The accumulated radiation dose for the surgeon was significantly higher in the non-navigated group; up to 9.96 times. The radiation dose for the patient was higher with the freehand technique, 1884.8 cGy·cm (non-navigated) versus 887 cGy·cm (navigated), without reaching a statistically significant level.Radiation exposure to the surgeon during pedicle screw placement with the freehand technique is up to 9.96 times greater than with the use of navigation. In the latter group, the only radiation exposure comes from the preoperative-level control and positioning of the 3D C-arm before 3D fluoroscopic acquisition. Furthermore, neuronavigation also reduces the cumulative dose for the patient.2.

a b s t r a c t Introduction: Concerning the preoperative clinical diagnostic work-up of glioma patients, tumor hetero- geneity challenges the oncological therapy. The current study assesses the performance of a multimodal imaging approach to differentiate between areas in malignant gliomas and to investigate the extent to which such a combinatorial imaging approach might predict the underlying histology. Methods: Prior to surgical resection, patients harboring intracranial gliomas underwent MRIs (MR-S, PWI) and 18 F-FET-PETs. Intratumoral and peritumoral biopsy targets were defined, by MRI only, by FET-PET only, and by MRI and FET-PET combined, and biopsied prior to surgical resection and which then received separate histopathological examinations. Results: In total, 38 tissue samples were acquired (seven glioblastomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma, one diffuse astrocytoma, and one oligoastrocytoma) and underwent histopathological analysis. The highest mean values of Mib1 and CD31 were found in the target point "T' defined by MRI and FET-PET combined. A significant correlation between NAA/Cr and PET tracer uptake (−0.845, p < 0.05) as well as Cho/Cr ratio and cell density (0.742, p < 0.05) and NAA/Cr ratio and MIB-1 (−0761, p < 0.05) was disclosed for this target point, though not for target points defined by MRI and FET-PET alone. Conclusion: Multimodal-imaging-guided stereotactic biopsy correlated more with histological malig- nancy indices, such as cell density and MIB-1 labeling, than targets that were based solely on the highest amino acid uptake or contrast enhancement on MRI. The results of our study indicate that a combined PET-MR multimodal imaging approach bears potential benefits in detecting glioma heterogeneity.

Purpose: Magnetic resonance imaging (MRI) is the gold standard in visualizing brain tumors and their effects on adjacent structures. However, no reliable information concerning different tumor components and borders between perifocal edema and infiltration areas can be received. The aim of the study was to establish and evaluate a multimodal imaging concept, in order to differentiate different biological tumor components and to determine tumor borders. Materials and Methods: 12 patients with cerebral gliomas (four low and eight high grade) received a “morphological” MRI, a 3D MR spectroscopy and a T2* MR perfusion examination prior to surgery. Data was evaluated by defining different tumor components, which were entitled based upon their multimodal characteristics and histological data. Results: In high grade gliomas different components can be differentiated, which were described as: “true edema”, “cellular proliferation”, “vascular proliferation”, “cellular infiltration”, “tumor” and “necrosis”. In low grade gliomas, four different tumor components were found: “true edema”, “cellular infiltration”, “cellular proliferation” and “tumor”. Conclusion: With the applied multimodal imaging and a novel evaluation concept, it was possible to detect different tumor components, which could be helpful in detecting the optimal sites for tumor biopsy. Especially in morphological “edema appearing” sites, this knowledge could be important for the adaption of tumor resection borders and the planning of radiation therapy. Further studies with more patients and histological correlation are needed.

Object Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits. Methods Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded. Results One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21–89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0–338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003). Conclusions This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.

Aldehyde dehydrogenase 1 (ALDH1) has been used to isolate tumorigenic stem-like cells in a large number of tumors, including glioblastoma multiforme (GBM). We recently showed that human glioblastoma cells with high ALDH1 (ALDH1(high)) activity contain stem-cell-like characteristics. In the study reported here, we isolated established and primary human glioblastoma cells based on their ALDH1 expression. When tested for asymmetric division, only cells with ALDH1(high) expression were able to restore heterogeneous populations after a few days, whereas cells with ALDH1(low) levels could not. Most interestingly, the capacity of cells with ALDH1(low) levels to divide asymmetrically into cells with either ALDH1(high) or ALDH1(low) expression could be restored after exposure to hypoxic culture conditions. Consequently, we found neurosphere formation reinstated in posthypoxic, formerly ALDH1(low), cells. The direct involvement of ALDH1 could be confirmed by ALDH1 small hairpin ribonucleic acid (shRNA) knockdown, suggesting ALDH1 as an intracellular marker for the identification and isolation of stem-like glioblastoma cells. In summary, we show that ALDH1 expression correlates well with asymmetric division capacity and tumor sphere formation. Furthermore, we demonstrated that hypoxic culture conditions induce and/or upregulate ALDH1 expression in established and primary GBM cell lines.

Surgery of lumbar disc herniations is one of the most common neurosurgical procedures. New surgical approaches and techniques are constantly evolving. We present our long-term follow-up results comparing standard open microdiscectomy (SOMD) and minimal access microdiscectomy (MAMD) for single-level lumbar disc herniations. Patients were randomized in two groups receiving either MAMD or SOMD. Physical and mental health and pain relief were assessed (ODI, SF-36 questionnaire, VAS leg and back pain). In addition, all patients received MR imaging for morphological evaluation of postoperative peridural scar tissue formation. Of the 60 initial patients (SOMD: 30 pts, MAMD: 30 pts), 38 were available for long-term follow-up. Mean follow-up time was 33 months. Long-term follow-up revealed significant postoperative pain relief in both groups. Good to excellent results concerning physical and mental health and pain relief were achieved in both groups. Significantly less peridural scar tissue formation was observed in the MAMD patients, but without clinical impact. MAMD is a feasible alternative to the standard open approach. Both groups show significant and long-lasting pain relief and good to excellent results regarding health-related quality of life. Congruent to our short-term results, we observed slightly but not statistically significant better clinical results in the MAMD group when compared to the SOMD group.

Object The aim of surgical glioma treatment is the complete resection of tumor tissue while preserving neurological function. Surgery-related neurological deficits arise from direct damage to the cortical or subcortical structures or from ischemia. The authors aimed to assess the incidence of resection-related ischemia of newly diagnosed or recurrent supratentorial gliomas and the sensitivity of intraoperative neuromonitoring (IOM) of motor evoked potentials (MEPs) for detecting such ischemic events and their influence on neurological motor function. Methods Between January 2009 and December 2010, 70 patients with tumors in motor-eloquent brain areas underwent intraoperative MEP monitoring during glioma resection and were examined by early postoperative MRI including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping. Postoperative areas of restricted diffusion were assessed by investigators blinded to the course of intraoperative MEPs and the neurological course. Results Among the 70 enrolled patients, a MEP amplitude decline below 50% of the baseline level was observed in 21 patients (30%). Sixteen of these patients (76%) had ischemic lesions identified on postoperative MRI scans. Forty-nine patients (70%) showed no decline in MEP amplitude, and only 16 (33%) of these patients harbored ischemic lesions. Moreover, 9 (69%) of 13 patients with a permanent loss of MEP amplitude showed postoperative ischemic lesions. Factors that promoted the occurrence of postoperative infarction were previous radiotherapy and location of the tumor close to the central arteries. Conclusions Alterations in the MEP amplitude during tumor resection and postoperative ischemic lesions are associated with postoperative impairment of motor function. Rather than cortical or subcortical structural damage of eloquent brain tissue alone, peri- or postoperative ischemic lesions play a crucial role in the development of surgery-related motor deficits.

Hypoxia plays a central role in tumor stem cell genesis and is related to a more malignant tumor phenotype, therapy resistance (e.g. in anti-angiogenic therapies) and radio-insensitivity. Reliable hypoxia imaging would provide crucial metabolic information in the diagnostic work-up of brain tumors. In this study, we applied a novel BOLD-based MRI method for the measurement of relative oxygen extraction fraction (rOEF) in glioma patients and investigated potential benefits and drawbacks. Forty-five glioma patients were examined preoperatively in a pilot study on a 3T MR scanner. rOEF was calculated from quantitative transverse relaxation rates (T2, T2*) and cerebral blood volume (CBV) using a quantitative BOLD approach. rOEF maps were assessed visually and by means of a volume of interest (VOI) analysis. In six cases, MRI-targeted biopsy samples were analyzed using HIF-1α-immunohistochemistry. rOEF maps could be obtained with a diagnostic quality. Focal spots with high rOEF values were observed in the majority of high-grade tumors but in none of the low-grade tumors. VOI analysis revealed potentially hypoxic tumor regions with high rOEF in contrast-enhancing tumor regions as well as in the non-enhancing infiltration zone. Systematic bias was found as a result of non-BOLD susceptibility effects (T2*) and contrast agent leakage affecting CBV. Histological samples demonstrated reasonable correspondence between MRI characteristics and HIF-1α-staining. The presented method of rOEF imaging is a promising tool for the metabolic characterization of human glioma. For the interpretation of rOEF maps, confounding factors must be considered, with a special focus on CBV measurements in the presence of contrast agent leakage. Further validation involving a bigger cohort and extended immuno-histochemical correlation is required.

Object The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function. Methods Patients who underwent glioma resection for newly diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded. Results New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p < 0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than in patients with newly diagnosed tumors. Patients with neurological deficits had a significantly higher rate of ischemic lesions. Conclusions Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (SAH) WFNS grade V is commonly known to be associated with high mortality and a very poor prognosis for survivors. Therefore, maximal invasive therapy is frequently delayed until any spontaneous improvement with or without an external ventricular drainage occurs. The aim of the study was to verify possible predictive factors and the probability of a favourable outcome in maximally treated patients. METHODS: One hundred and thirty-eight consecutive patients with WFNS grade V SAH were admitted between 03/2006 and 12/2010. Thirty-five patients died before aggressive therapy could proceed. One hundred and three patients received maximal treatment and were retrospectively evaluated. The outcome was assessed at discharge and in the follow-up with the Glasgow Outcome Scale. Univariate and multivariate linear regression models were performed to find predictors for an unfavourable outcome. RESULTS: Despite treatment, early mortality was 30 % (n = 31). At discharge, the rate of both vegetative and severely disabled patients was 27 % (n = 28). Favourable outcome at discharge was observed in 16 % (n = 16) of cases, whereas in the follow-up it rose to 26 % (n = 27). Multivariate full model regression identified intraventricular haematoma (IVH) and increasing age as independently predictive for poor outcome. CONCLUSIONS: Despite treatment, initial mortality and severe disability remain high. Nevertheless, a favourable outcome was achieved in 26 % of aggressively treated patients, rendering the withdrawal of maximal therapy for WFNS grade V SAH patients unacceptable today. In cases of old patients with IVH, the indication for aggressive therapy should be put in place more carefully due to a very poor prognosis

Up to now, navigated transcranial magnetic stimulation (nTMS) has been used for motor mapping in the vicinity of rolandic brain lesions. Recently, nTMS has also been suggested to be useful in mapping human language areas. The authors describe the case of a left-handed patient with a left-side glioblastoma within the opercular inferior frontal gyrus who presented with severe motor aphasia. Preoperative functional MRI (fMRI) indicated speech dominance of the right hemisphere and did not show any language-related activation in the vicinity of the tumor. Navigated TMS, however, showed a significantly higher rate of induced speech arrests for the left than for the right. Left-side direct cortical stimulation induced clear speech arrests during awake surgery. This case suggests that nTMS may be useful for preoperative speech mapping in tumors affecting the anatomy, vasculature, and brain oxygen levels and therefore impairing fMRI reliability.

Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined.While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average.Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

Diffusion tensor imaging fiber tracking (DTI FT) is used to visualize subcortical fiber tracts. Yet, there is no standard at hand to visualize language-involved subcortical fibers reliably. Thus, this study investigates the feasibility of using language-related cortical areas identified via repetitive navigated transcranial magnetic stimulation (rTMS) to seed DTI FT of subcortical language tracts. From 2011 to 2014, 37 patients with left-hemispheric perisylvian lesions were examined. Language-positive rTMS stimulation spots were integrated in the deterministic tractography software (BrainLAB, iPlanNet 3.0) as objects and used as seed regions for DTI FT. Tractography was then performed in each patient with 77 different combinations of fiber lengths (40 - 100 mm) and fractional anisotropy (FA; 0.01 - 0.5). The rTMS-based DTI FT identified all commonly known subcortical language tracts, such as the corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and the fronto-occipital fascicle. In 32 patients (86.5 %), each above-named tract could be visualized, while at least 6 out of these 9 tracts were identified in each patient. A fiber length of 100 mm and an FA of 0.1 or 0.15 provided optimal visualization by revealing 125 and 61 individually tracked fibers per visualized language tract and 90 % and 73 % of all language-related tracts, respectively. This study proves the feasibility of rTMS-based DTI FT for subcortical language tracts, provides suitable settings, and shows its easy and standardizable application for the visualization of every language tract in 86.5 % of patients.

// Stefanie Bette 1 , Benedikt Wiestler 1 , Johannes Kaesmacher 1 , Thomas Huber 1 , Julia Gerhardt 2 , Melanie Barz 2 , Claire Delbridge 3 , Yu-Mi Ryang 2 , Florian Ringel 2 , Claus Zimmer 1 , Bernhard Meyer 2 , Tobias Boeckh-Behrens 1 , Jan S. Kirschke 1 , Jens Gempt 2 1 Department of Neuroradiology, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany 2 Department of Neurosurgery, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany 3 Department of Neuropathology, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany Correspondence to: Stefanie Bette, email: stefanie.bette@tum.de Keywords: glioblastoma, infarct volume, karnofsky performance score, overall survival Received: June 04, 2016 Accepted: July 29, 2016 Published: August 22, 2016 ABSTRACT Postoperative ischemia is associated with reduced functional independence measured by karnofsky performance score (KPS), which correlates well with overall survival. Other studies suggest that postoperative hypoxia might initiate infiltrative tumor growth. Therefore, aim of this study was to analyze the impact of infarct volume on overall survival and progression free survival (PFS) of glioblastoma patients. 251 patients with surgery for a newly diagnosed glioblastoma (WHO IV) were retrospectively assessed. Pre- and postoperative KPS, date of death/last follow-up and histopathological markers were recorded. Pre- and postoperative tumor volume and the volume of postoperative infarction were manually segmented. A significant correlation of infarct volume with postoperative KPS decrease ( P = 0.001) was observed. Infarct volume showed a significant impact on overall survival ( P = 0.014), but not on PFS ( P = 0.112) in univariate analysis. This effect increased in the subgroup of patients with near-total tumor resection (> 90%) (overall survival: P = 0.006, PFS: P = 0.066). Infarct volume remained as an independent prognostic factor for overall survival in multivariate analysis (HR 1.013 [1.000–1.026], P = 0.042) including other prognostic factors (age, extent of resection, postoperative KPS). Postoperative infarct volume significantly correlates as an independent factor with overall survival after glioblastoma surgery. Besides the influence of perioperative infarction on postoperative KPS, postoperative hypoxia might also have an effect on tumor biology initiating infiltrative growth and therefore impaired survival.

Objective Total disc replacement (TDR) is typically indicated in young patients with a cervical soft disc herniation. There are few data on the activity level of patients after cervical TDR, in particular from young patients who are expected to have a high activity level with frequent exercising. The expectation is that returning to active sports after cervical TDR is not restricted. Methods Fifty patients were treated with a monosegmental cervical TDR at our department between May 2006 and March 2012. Clinical status and radiographic parameters were evaluated preoperatively and during follow-up. In addition, information was gathered regarding neck disability index, pain, a questionnaire concerning athletic aspects, and a modified Tegner activity score. The study design was a prospective case series. Results All patients were treated with the Prestige artificial cervical disc for a single-level soft disc herniation with radiculopathy. The average age was 40 years, and the mean follow-up period was 53 months (range, 26–96). The median neck disability index during follow-up was 5, and median visual analog scale for pain was 2. Two professional athletes, 20 semiprofessionals, 24 hobby athletes, and 5 patients with a very low activity level were treated. The median time to resumption of sporting activity was 4 weeks after surgery. All professionals and semiprofessionals recovered to their previous activity level. All of the 20 hobby athletes recovered to resume their sport participation. The modified Tegner preoperative score was 4 and the postoperative score was 3.5 ( P = 0.806). Conclusions We found that cervical TDR did not prohibit sporting activities. All patients recovered and were able to take part in their previous activities at an appropriate intensity level.

Objective To evaluate whether preoperative multirow detector computed tomography (MDCT) findings were associated with clinical outcome 24 months after dynamic stabilization for painful degenerative lumbar spine disease. Methods Preoperative MDCT examinations of 63 patients (66 ± 11.7 years; 60% women) treated with a dynamic screw rod system for painful degenerative segmental instability with/without spinal stenosis were assessed for quantitative and qualitative parameters defining degenerative changes of the thoracolumbar spine, including grades of disc herniation, degenerative spondylolisthesis, vertebral body sclerosis, cross-sectional area of the spinal canal at disc level, intervertebral disc height, ancillary bone mineral density, and anteroposterior diameter of intervertebral foramina. Clinical performance was assessed at baseline and 24 months with quantitative scales, including the Oswestry Disability Index and Short-Form 36 physical component summary. For statistical analysis classification and regression trees, linear regression and nonparametric tests were used. Results Clinical scores improved substantially over 24 months compared with preoperative values (delta Oswestry Disability Index −32.1 ± 17.2, delta Short-Form 36 physical component summary 4.9 ± 2.3). Physical component summary improvement was significantly better in patients with lower grades of disc herniation ( P P = 0.011), lower cross-sectional area of the spinal canal ( P = 0.043), high intervertebral disc height ( P = 0.006), and high grades of vertebral body sclerosis ( P = 0.002). Patients with high bone mineral density and initially low diameter of intervertebral foramina showed a significantly better improvement of Oswestry Disability Index ( P Conclusions Clinical improvement after dynamic stabilization was significantly associated with 7 independent baseline imaging findings. Preoperative evaluation of these MDCT parameters may improve therapy selection for patients with degenerative lumbar spine disease.

OBJECTIVE Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain. METHODS Between 2010 and 2013, nTMS motor mapping was performed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered. RESULTS Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location–dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect. CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

Repetitive navigated transcranial magnetic stimulation (rTMS) can be used for preoperative language mapping, but it still suffers from comparatively high sensitivity and low specificity when compared to direct cortical stimulation (DCS). Therefore, this study evaluates whether the additional consideration of rTMS-based diffusion tensor imaging fiber tracking (DTI FT) for identifying language-positive brain regions improves specificity when compared to DCS. We performed rTMS, rTMS-based DTI FT, and DCS during awake surgery combined with object naming in 20 patients suffering from left-sided perisylvian brain lesions. For rTMS, different error rate thresholds (ERTs) and error types were considered, and DTI FT was conducted with individualized fractional anisotropy thresholds (FATs). Then, receiver operating characteristics (ROC) for rTMS vs. DCS, rTMS-based DTI FT vs. DCS, and rTMS spots confirmed by rTMS-based DTI FT vs. DCS were calculated. In general, rTMS vs. DCS was in good accordance with previous literature (sensitivity/specificity: 92.7/13.3 % for all naming errors without ERT). In addition, rTMS-based DTI FT vs. DCS led to balanced results when tracking was based on all errors as well (sensitivity/specificity: 62.8/64.3 % for 100 % FAT). However, rTMS combined with rTMS-based DTI FT vs. DCS did not lead to any improvement in specificity when compared to rTMS vs. DCS alone. The additional use of rTMS-based DTI FT to rTMS did not improve the identification of DCS-positive language areas during awake surgery. Yet, concerning rTMS-based DTI FT, this new technique must be validated itself by intraoperative subcortical stimulation.

BACKGROUND: While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recurrent glioblastomas on patient survival. METHODS: In a multicenter retrospective-design study, patients with primary glioblastomas undergoing repeat resections for recurrent tumors were evaluated for factors affecting survival. Age, Karnofsky performance status (KPS), extent of resection (EOR), tumor location, and complications were assessed. RESULTS: Five hundred and three patients (initially diagnosed between 2006 and 2010) undergoing resections for recurrent glioblastoma at 20 institutions were included in the study. The patients' median overall survival after initial diagnosis was 25.0 months and 11.9 months after first re-resection. The following parameters were found to influence survival significantly after first re-resection: preoperative and postoperative KPS, EOR of first re-resection, and chemotherapy after first re-resection. The rate of permanent new deficits after first re-resection was 8%. CONCLUSION: The present study supports the view that surgical resections of recurrent glioblastomas may help to prolong patient survival at an acceptable complication rate.

The introduction of the European Working Time directive 2003/88/EC has led to a reduction of the working hours with distinct impact on the clinical and surgical activity of neurosurgical residents in training. METHODS: A survey was performed among European neurosurgical residents between 06/2014 and 03/2015. Multiple logistic regression was used to assess the relationship between responder-specific variables (e.g., age, gender, country, postgraduate year (PGY)) and outcome (e.g., working time). RESULTS: A total of 652 responses were collected, of which n = 532 responses were taken into consideration. In total, 17.5, 22.1, 29.5, 19.5, 5.9, and 5.5 % of European residents indicated to work 80 h/week, respectively. Residents from France and Turkey (OR 4.72, 95 % CI 1.29-17.17, p = 0.019) and Germany (OR 2.06, 95 % CI 1.15-3.67, p = 0.014) were more likely to work >60 h/week than residents from other European countries. In total, 29 % of European residents were satisfied with their current working time, 11.3 % indicated to prefer reduced working time. More than half (55 %) would prefer to work more hours/week if this would improve their clinical education. Residents that rated their operative exposure as insufficient were 2.3 times as likely as others to be willing to work more hours (OR 2.32, 95 % CI 1.47-3.70, p 50 % of his/her working time in the operating room. By contrast, 77.4 % indicate to devote >25 % of their daily working time to administrative work. For every advanced PGY, the likelihood to spend >50 % of the working time in the OR increases by 19 % (OR 1.19, 95 % CI 1.02-1.40, p = 0.024) and the likelihood to spend >50 % of the working time with administrative work decreases by 18 % (OR 0.84, 95 % CI 0.76-0.94, p = 0.002). CONCLUSIONS: The results of this survey on >500 European neurosurgical residents clearly prove that less than 40 % conform with the 48-h week as claimed by the WTD2003/88/EC. Still, more than half of them would chose to work even more hours/week if their clinical education were to improve; probably due to subjective impression of insufficient training. KEYWORDS

Summary Objective Navigated transcranial magnetic stimulation (nTMS) is a newly evolving technique. Despite its supposed purpose of preoperative mapping of the central region, little is known about further applications as well as the accuracy compared to more commonly used modalities like direct cortical stimulation (DCS) and functional MRI (fMRI). Methods We examined 30 patients with tumors in or close to the precentral gyrus as well as in the subcortical white matter motor tract using nTMS with the Nexstim eXimia system. Data was sent to the neuronavigation system and correlated with intraoperative direct cortical stimulation. Results In the cases of lesions of the precentral gyrus, preoperative motor cortex characterization correlated well with intraoperative DCS with a deviation of 4.5 ± 3.5 mm. When comparing nTMS with fMRI however, deviation was quite larger with 9.6 ± 7.9 mm for upper and 15.0 ± 12.8 mm for lower extremity. In patients with subcortical lesions DTI fiber tracking was performed using nTMS mapping as seed region, which resulted in a subjectively more specific presentation of the corticospinal tract compared to conventional fiber tracking and caused less interobserver variability. Conclusion Navigated TMS correlates well with DCS as the best established standard despite many factors, which are supposed to contribute to inaccuracy of the method. Moreover, nTMS-aided DTI fiber tracking is user-independent and, therefore, a method for further standardization of DTI fiber tracking.

Despite the increased risk of hemorrhage and deteriorating neurological function of once-bled cerebral cavernous malformations (CM), the management of eloquently located CMs remains controversial. All eloquently located CMs (n = 45) surgically treated between 03/2006 and 04/2011 in our department were consecutively evaluated. Eloquence was characterized according to Spetzler and Martin's definition. The following locations were approached: brainstem, n = 16; sensorimotor, n = 8; visual pathway, n = 7; cerebellum (deep nuclei and peduncles), n = 7; basal ganglia, n = 4, and language, n = 3. Follow-up data was available for 41 patients (91 %) with a median interval of 14 months. Outcomes were evaluated according to the Glasgow outcome and the modified Rankin scale. Immediately after surgery, 47 % (n = 21) had a new deficit. At follow-up, 80 % (n = 36) recovered to at least preoperative status or were better than before surgery, 9 % (n = 4) exhibited a slight, and 7 % (n = 3) had a moderate neurological impairment. Only two cases (4 %) with a new permanent severe deficit were observed, both related to dorsal brainstem surgery. The outcome after the surgery of otherwise located brainstem CMs was as beneficial as that for non-brainstem CMs. Patients with initially poor neurological performance fared worse than oligosymptomatic patients. Despite the high postoperative transient morbidity, the majority improved profoundly during follow-ups. Compared with natural history, surgical treatment should be considered for all eloquent symptomatic CMs. Dorsal brainstem location and poor preoperative neurological status are associated with an increased postoperative morbidity.

Single-center prospective randomized controlled study.To evaluate the accuracy of robot-assisted (RO) implantation of lumbar/sacral pedicle screws in comparison with the freehand (FH) conventional technique.SpineAssist is a miniature robot for the implantation of thoracic, lumbar, and sacral pedicle screws. The system, studied in cadaver and cohort studies, revealed a high accuracy, so far. A direct comparison of the robot assistance with the FH technique is missing.Patients requiring mono- or bisegmental lumbar or lumbosacral stabilization were randomized in a 1:1 ratio to FH or RO pedicle screw implantation. Instrumentation was performed using fluoroscopic guidance (FH) or robot assistance. The primary end point screw position was assessed by a postoperative computed tomography, and screw position was classified (A: no cortical violation; B: cortical breach2 mm; C: ≥2 mm to4 mm; D: ≥4 mm to6 mm; E: ≥6 mm). Secondary end points as radiation exposure, duration of surgery/planning, and hospital stay were assessed.A total of 298 pedicle screws were implanted in 60 patients (FH, 152; RO, 146). Ninety-three percent had good positions (A or B) in FH, and 85% in RO. Preparation time in the operating room (OR), overall OR time, and intraoperative radiation time were not different for both groups. Surgical time for screw placement was significantly shorter for FH (84 minutes) than for RO (95 minutes). Ten RO screws required an intraoperative conversion to the FH. One FH screw needed a secondary revision.In this study, the accuracy of the conventional FH technique was superior to the RO technique. Most malpositioned screws of the RO group showed a lateral deviation. Attachment of the robot to the spine seems a vulnerable aspect potentially leading to screw malposition as well as slipping of the implantation cannula at the screw entrance point.