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INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (nGBM). A crucial parameter for TTFields efficacy is compliance to treatment. In this prospective study, we assessed 5 psychological domains known to influence treatment compliance using a standardized interview in nGBM patients. The results of this psychological assessment were correlated to TTF compliance. METHODS A cohort of 49 nGBM patients (female 22; male 27, median age 62 years) were recruited. Most patients received a gross total resection (51%), the postsurgical treatment consisted of concomitant radiochemotherapy plus TTF in most cases (81%), only 2 patients received chemotherapy only, and 7 patients were additionally enrolled in clinical drug trials. The psychological assessment system consisted of 5 domains: Social support, confidence in treatment efficacy, communication status about treatment, anxiety, and depression. The interview was repeated every 8 weeks over a period of 8 months or if patients stopped treatment or developed second tumor progression. Additional phone interviews were conducted every 4 weeks. RESULTS Median and mean compliance was 98% and 81.6%, respectively (range 5%-100%), drops of compliance below 75%, which were classified as a threshold value, occurred 2259 times. Over-dispersed Poisson and multivariate negative binomial regression analysis revealed depression to be significantly correlated with the number of drops below 75% and with the mean compliance in the first 4 months of treatment. In addition, at later time points, confidence in treatment efficacy significantly correlated with the number of drops below 75%. All other domains did not appear to be associated with TTF treatment compliance. CONCLUSION Overall, compliance to TTF was high, however, drops below 75% of compliance occurred frequently during the measurement periods. In the initial treatment phase, depression was associated with these events, whereas confidence in treatment efficacy was correlated at later time points.

Background and Study Aims Aneurysm clips must have adequate closing forces because residual blood flow in clipped aneurysms may result in aneurysm recurrence. Such flow can be intraoperatively detected by visual inspection, microvascular Doppler sonography, indocyanine green videoangiography (ICG-V), angiography, and puncture. Patients We present two patients with ruptured very small middle cerebral artery aneurysms (3 and 2.9 mm). The necks of both aneurysms were microsurgically clipped with Yasargil aneurysm clips without any complications. Results In both aneurysms, visual inspection suggested complete occlusion, but ICG-V showed persistent residual blood flow between the middle parts of the clip blades.The first patient was treated with a 5.4-mm FT744T clip (closing force of 1.47 N). After the ICG-V finding, a second 3.9-mm FT714T clip (closing force of 1.08 N) was placed on the tips of the already implanted clip to increase the closing forces. Subsequent ICG-V did not show any further residual blood flow. In the second patient, the aneurysm was clipped with an 8.0-mm FE764K clip (closing force of 1.77 N). Intraoperative ICG-V showed persistent residual blood flow within the aneurysmal dome despite complete closure of the clip. The clip was repositioned closer to the parent vessel. Consecutive ICG-V did not show any residual blood flow. Conclusion Visually undetected incomplete aneurysm occlusion can be revealed with ICG-V. In very small aneurysms, standard closing forces of clips may not be sufficient and complete closure of the clip branches should be intraoperatively validated with ICG-V.

Infectious spondylodiscitis of the lumbar spine is a common serious disease for which evidence-based therapeutic concepts are still lacking.This retrospective study compared the impact of the health status of patients on the length of hospital stay with regard to the treatment concept, i.e., antibiotic therapy or antibiotic therapy in combination with fixation surgery.The study included 54 consecutive patients with infectious spondylodiscitis of the lumbar spine who had been treated at our clinic between 2004 and 2013. Records included patient demographics, concomitant diseases, the neurological status and treatment modality, and the length of hospital stay.40 men and 14 women with a mean age of 64.2 (30-89) years were included. 13 patients were only treated with antibiotics (group A), 7 patients with abscess decompression (group B), 18 patients with early dorsal fusion (10 days after admission) (group C), and 16 patients with late dorsal fusion (≥10 days after admission; group D). Patients undergoing early dorsal fusion had a significantly shorter hospital stay (33.2 days) than patients undergoing late dorsal fusion (57.0 days), P = 0.016. Mean hospital stay of patients treated with antibiotics was 30.3 days, that of patients receiving abscess decompression 57.8 days. Patients receiving only antibiotics had a significantly lower CRP level at admission than patients undergoing early fusion, P0.05.Patients with one or more relevant chronic concomitant diseases showed faster recovery, shorter hospital stays, and earlier return to daily routine after early dorsal fusion than after late dorsal fusion or abscess evacuation alone.

The demographic change results in an ever increasing number of older patients with pre-existing medical conditions who require spinal surgery, and recovery is often severely impaired by procedure-related complications. The purpose of this retrospective study was to determine patients at risk of medical and surgical complications.Using our database, we reviewed 1244 patients with lumbar degenerative disk disease, spinal stenosis, and instability, who had undergone surgery at our department between 2009 and 2014. We screened for medical complications (thromboembolic and cardiac events, pneumonia, and sepsis) and surgical complications (hemorrhage, wound infection, and CSF fistula). Furthermore, a matched 1:1 control group consisted of 103 patients without any surgical and medical complications in the randomly selected period of May 2009 to October 2014.93 patients (46 women, 47 men), mean age 70 years (range 33-86 years, median 67.4 years), with complications were identified (overall morbidity 7.6 %): 22.6 % (n = 26) had medical complications and 77.4 % (n = 89) surgical complications. In 93 patients (46 females, 47 males), mean age 70 years (range 33-86 years, median 67.4 years), a total of 115 complications were noted (overall morbidity of the 93 patients 7.6 %): 22.6 % (n = 26) medical complications and 77.4 % (n = 89) surgical complications. Age and pre-existing conditions were independently associated with medical complications (p lt; 0.001). Infections (pneumonia and sepsis) were correlated with multi-segmental interventions (p = 0.009), duration of surgery (p = 0.009), and pre-existing conditions (p = 0.014). Surgical complications were significantly correlated with age (p = 0.016) and duration of surgery (p = 0.014) and occurred significantly more often in patients with instability (p lt; 0.001). Wound healing disorders were associated with coagulopathy (p = 0.013) and transfusion (p lt; 0.001).We identified predictors that help identify patients at risk of medical and surgical complications. These correlations should be taken into account when advising older patients with pre-existing conditions on lumbar spine surgery.

The aim of this paper is to provide a comprehensive overview of the MICCAI 2020 AutoImplant Challenge. The approaches and publications submitted and accepted within the challenge will be summarized and reported, highlighting common algorithmic trends and algorithmic diversity. Furthermore, the evaluation results will be presented, compared and discussed in regard to the challenge aim: seeking for low cost, fast and fully automated solutions for cranial implant design. Based on feedback from collaborating neurosurgeons, this paper concludes by stating open issues and post-challenge requirements for intra-operative use. The codes can be found at https://github.com/Jianningli/tmi .

The multidisciplinary management of patients with brain metastases (BM) consists of surgical resection, different radiation treatment modalities, cytotoxic chemotherapy, and targeted molecular treatment. This review presents the current state of neurosurgical technology applied to achieve maximal resection with minimal morbidity as a treatment paradigm in patients with BM. In addition, we discuss the contribution of neurosurgical resection on functional outcome, advanced systemic treatment strategies, and enhanced understanding of the tumor biology.

(1) Background—Mapping language using direct cortical stimulation (DCS) during an awake craniotomy is difficult without using more than one language paradigm that particularly follows the demand of DCS by not exceeding the assessment time of 4 s to prevent intraoperative complications. We designed an intraoperative language paradigm by combining classical picture naming and verb generation, which safely engaged highly relevant language functions. (2) Methods—An evaluation study investigated whether a single trial of the language task could be performed in less than 4 s in 30 healthy subjects and whether the suggested language paradigm sufficiently pictured the cortical language network using functional magnetic resonance imaging (fMRI) in 12 healthy subjects. In a feasibility study, 24 brain tumor patients conducted the language task during an awake craniotomy. The patients’ neuropsychological outcomes were monitored before and after surgery. (3) Results—The fMRI results in healthy subjects showed activations in a language-associated network around the (left) sylvian fissure. Single language trials could be performed within 4 s. Intraoperatively, all tumor patients showed DCS-induced language errors while conducting the novel language task. Postoperatively, mild neuropsychological impairments appeared compared to the presurgical assessment. (4) Conclusions—These data support the use of a novel language paradigm that safely monitors highly relevant language functions intraoperatively, which can consequently minimize negative postoperative neuropsychological outcomes.

In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups (p = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 vs. B: 8.12 months; p = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival (p = 0.00001). However, elderly patients less frequently received systemic treatment (p = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score (p = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.

INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (GBM). One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity, which depends on the dielectric properties of the tumor tissue. In this study we determined the dielectric properties of GBM by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor were analyzed separately. METHODS A cohort of 38 patients with newly diagnosed GBM were analyzed. Tissue probes were acquired from the vital tumor area and perinecrotic compartment. The tissue was measured immediately to avoid artifacts. A fragment was dissected from each tissue sample and was placed into a cylindrical cell with a known diameter. The impedance was recorded at frequencies 20Hz-1MHz using a software specifically developed for this study, which controls the LCR meter. The measured impedance was translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe was fixed, and stained with H&E to visualize cellularity, luxol fast blue to analyze the myelinated fiber content and against factor VIII related antigen to assess tumor vascularity. RESULTS We found significant differences between the conductivity and permittivity of tissue samples from each individual tumor (mean conductivity [S/m]: 0.302; range: 0.607 – 0.100; mean permittivity [Farad/m]: 3519.8; range: 11182.5 – 135.7). Consistently, the perinecrotic areas displayed lower conductivity values compared to the solid tumor compartments. Histological analysis revealed significantly higher cellularity and lower myelinated fiber content in tissue samples with high conductivity and permittivity. CONCLUSION The dielectric properties of GBM show a high intratumoral heterogeneity which correlate to the extent of cellularity and myelin fiber content within the tissue.

Objectives We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging–MRI) but 18F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany). Patients and method Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area. Results In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted. Discussion and conclusion Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery.

Objectives White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson’s disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. Patients and methods 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. Results Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8 cm3 ± 18.836 vs. 9.3 cm3 ± 12.2; p = 0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p = 0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p = 0.006; R2 = 0.40) after correction for age. Conclusions Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.

Introduction Spinal schwannoma (SS) is the most frequently diagnosed benign spinal tumor, constituting approximately 25 % of all intradural tumors. Aim of our study was to identify factors that potentially affect immediate postoperative neurological outcome, and the rate of functional recovery within 12 months. Methods Screening of our institutional database yielded 90 consecutive patients (mean age 57.1 years, 39 women [43.3 %]) with newly diagnosed SS between March 1997 and October 2018. We pre- and postoperatively reviewed patient charts, surgical reports, radiographic data, use of IOM, duration of symptoms, histopathology, co-morbidities, radiographic extension, surgical strategy, neurological performance (Japanese Orthopedic Association Score [JOA score] and Frankel Grade Classification). Results Mean duration of preoperative symptoms was 3.6 ± 1.6 months. Most common symptoms were local pain (n = 77, 85.6 %). Macroscopic complete resection was achieved in 84 patients (93.3 %). During follow-up, complete recovery from local pain was documented for 41 patients (59.7 %), from radiating pain for 41 (69.5 %; p Postoperatively, 25 (27.7 %) patients developed a new neurological deficit (motor deficits n = 3 and sensory deficits n = 23; one patient developed both); after 12 months, however, motor deficits had abated in all patients, and 16 (69.5 %) patients had completely recovered from sensory deficits. Use of intraoperative monitoring (IOM) was a significant predictor for good functional outcome (p Conclusion Resection of SS accompanied by IOM whenever feasible should be advocated. We achieved a high number of complete resections with a low rate of morbidity. New postoperative motor or sensory deficits had a very high rate of complete recovery within 12 months.

BACKGROUND: Recently, tumor treating fields (TTFields) have been established as an effective new approach for the treatment of newly diagnosed GBM. One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity. Essentially, the higher the electric field intensity, the higher the tumor cell killing that can be achieved by TTFields. The electric properties of the normal intracranial compartments (cerebrospinal fluid, blood, white and grey mater) are well established, allowing the prediction of the electric field distribution by finite element mesh modelling. In contrast, there is no data available about the electric properties of tumor tissue, which leads to a lack of information regarding the electric field intensity within the tumor. In this study we will determine the dieclectric properties of malignant glioma by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor will be sampled and analyzed separately. MATERIAL AND METHODS: Twenty patients with high grade glioma currently being recruited. Tissue probes are acquired from the infiltration zone, vital tumor area, and perinecrotic compartment identified intraoperatively using neuronavigation, intraoperative ultrasound and fluorescence guidance. From each region, five tissue probes are sampled. Immediately after acquisition, the tissue is immediately to avoid artifacts by temperature change, change of fluid composition as well as post resection ischemia. A cylindrical fragment is dissected from each tissue sample and is placed into a cylindrical cell with a known diameter. Two parallel electrodes are placed on both sides of the sample and the thickness of the tissue is measured using a micrometer. The impedance is recorded at frequencies 20Hz-1MHz using a software specificly developed for this study, which controls the LCR meter (Keysight Technologies, Santa Rosa, USA). The measured impedance is then translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe will be fixed, H&E stained and histologically analyzed for tumor cell count and specific tissue features (infiltration into normal brain, vital tumor area, necrosis). RESULTS: The study has received a positive vote from the Ethical Board of the University Regensburg Medical Center. The first patients are being recruited, the actual results will be evaluated and presented during the meeting.

INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed GBM. One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity, which depends on the dielectric properties of the tumor tissue. In this study we determined the dielectric properties of brain tumors by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor were analyzed separately. METHODS A cohort of 84 patients with tumors of different histology have been recruited. Tissue probes were acquired from the vital tumor area and perinecrotic compartment. The tissue was measured immediately to avoid artifacts. A fragment was dissected from each tissue sample and was placed into a cylindrical cell with a known diameter. The impedance was recorded at frequencies 20Hz-1MHz using a software specifically developed for this study, which controls the LCR meter. The measured impedance was translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe was fixed, H&E stained and histologically analyzed. RESULTS We found significant differences between the conductivity of different types of tumors with meningiomas showing the lowest conductivity (mean conductivity [S/m]: 0.193; range: 0.327 – 0.113) and GBM tissue exhibiting the highest conductivity values (mean conductivity [S/m]: 0.402; range: 0.893 – 0.157). Consistently, the perinecrotic areas displayed lower conductivity values compared to the solid tumor compartments. Also, we found a significant intratumoral heterogeneity in tumors of one specific histological diagnosis. CONCLUSION The dielectric properties of intracranial tumors appear to be depending on histological class and malignancy grade and show significant intratumoral heterogeneity. These results may allow a more precise modelling of electric field intensity distribution within the tumor.

Treatment of glioblastoma (GBM) consists of microsurgical resection followed by concomitant radiochemotherapy and adjuvant chemotherapy. The best outcome regarding progression free (PFS) and overall survival (OS) is achieved by maximal resection. The foundation of a specialized neuro-oncology care center (NOC) has enabled the implementation of a large technical portfolio including functional imaging, awake craniotomy, PET scanning, fluorescence-guided resection, and integrated postsurgical therapy. This study analyzed whether the technically improved neurosurgical treatment structure yields a higher rate of complete resection, thus ultimately improving patient outcome. Patients and methods: The study included 149 patients treated surgically for newly diagnosed GBM. The neurological performance score (NPS) and the Karnofsky performance score (KPS) were measured before and after resection. The extent of resection (EOR) was volumetrically quantified. Patients were stratified into two subcohorts: treated before (A) and after (B) the foundation of the Regensburg NOC. The EOR and the PFS and OS were evaluated. Results: Prognostic factors for PFS and OS were age, preoperative KPS, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase 1 (IDH1) mutation status and EOR. Patients with volumetrically defined complete resection had significantly better PFS (9.4 vs. 7.8 months; p = 0.042) and OS (18.4 vs. 14.5 months; p = 0.005) than patients with incomplete resection. The frequency of transient or permanent postoperative neurological deficits was not higher after complete resection in both subcohorts. The frequency of complete resection was significantly higher in subcohort B than in subcohort A (68.2% vs. 34.8%; p = 0.007). Accordingly, subcohort B showed significantly longer PFS (8.6 vs. 7.5 months; p = 0.010) and OS (18.7 vs. 12.4 months; p = 0.001). Multivariate Cox regression analysis showed complete resection, age, preoperative KPS, and MGMT promoter status as independent prognostic factors for PFS and OS. Our data show a higher frequency of complete resection in patients with GBM after the establishment of a series of technical developments that resulted in significantly better PFS and OS without increasing surgery-related morbidity.

BACKGROUND: After a positive randomized clinical trial showing significant survival benefits, Tumor Treating Fields (TTFields) have been implemented in the management of newly diagnosed glioblastoma (GBM). Biophysical modeling of TTField application has demonstrated a heterogeneous electric field distribution within the intracranial space, reaching maximal intensities at tissue borders with different electric conductivity. However, no imaging modality is available to visualize the impact of TTField treatment within the tumor and the bordering normal brain in each individual patient. Our hypothesis is that the distribution and field intensity may be highly heterogeneous between GBM patients depending on tumor size, resection status and perifocal edema. The goal of our study is to develop a voxel based imaging analysis tool, which may allow to detect specific changes induced by TTFields in GBM patients. MATERIAL AND METHODS: Structural MR-Data of 27 patients suffering from newly diagnosed GBM treated according to the Stupp protocol combined with TTFields and 27 control patients (matched for gender, age, IDH1 mutation and MGMT promoter methylation status) treated according to the Stupp protocol without TTFields. Imaging acquisition was conducted at 1.5 T MRI-Scanners at the Department of Neuroradiology of the University Regensburg Medical Center. For both patients groups a high-resolution T1-weigthed image (3D magnetization prepared rapid gradient echo) was acquired during disease control after the concomitant phase and after the first two cycles of adjuvant chemotherapy either with or without TTField treatment. To analyze group and therapy-induced longitudinal differences of grey and white matter density, individual MRI-T1-data sets were preprocessed using the (V)oxel (b)ased (M)orphmetry and D(iffeomorphic) A(natomical) R(egistration) T(hrough) E(xponentiated) L(ie) A(lgebra) toolboxes both implemented in (S)tatistical (P)arametric (M)apping 12 running under MaTLab R2016b. Possible group differences were subsequently assessed by parametric t-test for independent samples as well as within subject’s t-tests for determination of longitudinal therapy-inducing effects. RESULTS: The study has received a positive vote from the Ethical Board of the University Regensburg Medical Center. The first patients are being recruited, the actual results will be evaluated and presented during the meeting.

BACKGROUND Surgical resection of (GBM) has three goals: Tissue acquision to establish a histological and molecular diagnosis, prolongation of survival and improvement of neurological impairment. Regarding survival gain, complete resection is superior to incomplete resection. However, no data are available, whether complete resection also has a higher impact on neurological improvement rates compared to incomplete resection. The goal of our study was to compare the reduction of focal neurological deficits and improvement of functional independency in newly diagnosed GBM patients receiving a complete vs. incomplete resection. MATERIAL AND METHODS A cohort of 299 patients (mean age 60.6 year; female/male ratio 124/175) were included. Neurological and functional independence status was measured by the medical research neurological performance status (NPS), the Karnofsky performance score (KPS) and the presence of seizures. Focal neurological impairment regarding hemiparesis, aphasia visual field (VFD) and cranial nerve deficits (CND) was recorded and semi - quantitatively rated pre- and postoperatively as well as at follow up. The extent of resection (EOR) was analyzed using early postoperative MRI scanning and was classified in either complete (CR), incomplete (IR) resection. RESULTS The complete and incomplete resection groups were balanced regarding gender, age, preoperative KPS, MGMT and IDH1 status. Median overall survival (OS) was 14.5 months, showing a significant benefit of complete resection (17.9 vs. 11.5; p = 0.0001). Impaired KPS was detected in 87.9%, epileptic seizures were displayed by 31.4% of all patients, the most frequent focal deficit was aphasia with 25.1%, followed by CND (20.1%) and hemiparesis (17.1%). KPS was improved in 45.6%, seizures were reduced in 91.5%, the highest improvement of focal deficit was achieved in CND (71.7%) the lowest in VFD (44.8%). Complete resection did achieve a higher improvement rate in hemiparesis (79.1% vs. 49.8%; p = 0.03) and seizure activity (97.7% vs. 86.3%; p = 0.04). In all other domains the improvement rates after complete resection were not significantly different to incomplete resection. Finally, complete resection did not show a higher rate of postsurgical worsening rate in any of the domains. CONCLUSION Complete resection is safe and does convey superior improvement rates of epileptic seizures and hemiparesis.

Introduction: Recently, tumor treating fields (TTFields) have been established as for the treatment of newly diagnosed GBM1. One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity. The electric properties of the normal intracranial compartments are well established, allowing the prediction of the electric field distribution. In contrast, there is no data available about the electric properties of tumor tissue. In this study we determined the dieclectric properties of brain tumors by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor were sampled and analyzed separately. Methods: A cohort of thirty patients with tumors of different histology and malignancy grade have been recruited (meningioma: n=11; brain metastases n=7; low grade glioma n=6; glioblastoma n=6). Tissue probes were acquired whenever possible from the vital tumor area, and perinecrotic compartment identified intraoperatively using neuronavigation, intraoperative ultrasound and fluorescence guidance. From each region, five tissue probes were sampled. After acquisition, the tissue was measured immediately to avoid artifacts induced by temperature change, differences of fluid composition as well as post resection ischemia. A fragment was dissected from each tissue sample and was placed into a cylindrical cell with a known diameter. Two parallel electrodes were placed on both sides of the sample and the thickness of the tissue was measured using a micrometer. The impedance was recorded at frequencies 20Hz-1MHz using a software specifically developed for this study, which controls the LCR meter (Keysight Technologies, Santa Rosa, USA). The measured impedance was translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe was fixed, H&E stained and histologically analyzed for tumor cell count and specific tissue features. Results: After receiving a positive ethics votum, the first 30 patients were recruited. As a reference, grey and white matter tissue samples from mouse brains were used. We found significant differences between the tumor entities with meningiomas showing the lowest and GBM tissue the highest conductivity values. Consistently, the perinecrotic areas displayed lower conductivity values compared to the solid tumor compartment. Also, we found a significant heterogeneity in the dielectric properties within one tumor. Conclusion: The dielectric properties of intracranial tumors appear to be depending on histological class and malignancy grade and show significant intratumoral heterogeneity. These results may allow a more precise modelling of electric field intensity distribution within the Tumor. Citation Format: Martin A. Proescholdt, Amer Haj, Christian Doenitz, Alexander Brawanski, Zeev Bomzon, Hadas Sara Hershkovich. The dielectric properties of brain tumor tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4031.

Background Temporary anaesthesia or analgosedation used for awake craniotomies carry substantial risks like hemodynamic instabilities, airway obstruction, hypoventilation, nausea and vomiting, agitation, and interference with test performances. We tested the actual need for sedatives and opioids in 50 patients undergoing awake craniotomy for brain tumour resection in eloquent or motoric brain areas when cranial nerve blocks, permanent presence of a contact person, and therapeutic communication are provided.

In glioma surgery, the extent of resection (EOR) is one important predictor of progression-free survival. In 2006, fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) was shown to improve the EOR in malignant gliomas. However, the use of 5-ALA is complex and causes certain side effects. Sodium fluorescein (FL) is a fluorescent dye that is used for angiography in ophthalmic surgery. FL accumulates in areas of the disturbed blood-brain barrier and can be visualized under a 560-nm wavelength fluorescent light source (YELLOW 560 nm, Carl Zeiss Meditec, Oberkochen, Germany). Here, we present the first experiences with low-dose FL and YELLOW 560 nm in 35 patients with malignant brain tumors. A total of 200 mg of FL (3–4 mg/kg bodyweight) was administered in 35 patients during craniotomy as an off-label use between May and August 2012. We retrospectively analyzed the histology, pre-treatment, clinical parameters pre- and postoperatively and occurrence of any adverse effects. The feasibility and efficacy (‘helpful,’ ‘not helpful’) of FL under YELLOW 560 nm (demarcation of the tumor margin) was assessed by the responsible neurosurgeon (n = 5) for each surgical procedure. Twenty-six patients had gliomas (1 WHO grade I, 3 WHO grade II, 5 WHO grade III, 17 WHO grade IV), 5 patients had cerebral metastases, 2 had non-malignant astrogliosis and 2 had post-radiation necrosis. The fluorescence signal was detected in all patients immediately after the FL administration. FL application was classified as ‘helpful’ in 28 patients, implying improved visualization of the tumor margins. The intensity of the fluorescence signal seemed to be correlated to the histology and was strongly dependent on the pre-treatment status. We did not record any allergic reactions or any other adverse effects. The use of FL for the resection of brain tumors is safe and feasible. Presumably, the visualization of the tumor margin depends on the histopathology and on the pre-treatment status. A randomized evaluation of FL under the YELLOW 560 nm filter is planned to prospectively analyze the extent of resection in patients with malignant brain tumors.

Background Despite a broad clinical use, the mechanism of action of SCS is poorly understood. Current information suggests that the effects of SCS are mediated by a complex set of interactions at several levels of the nervous system including spinal and supraspinal mechanisms. Aims The study was undertaken to investigate the influence of SCS on distinct parameters of cortical excitability using single- and paired-pulse transcranial magnetic stimulation (TMS). Methods Five patients with chronic neuropathic pain were examined with the SCS stimulator on and off by means of TMS. Pain was assessed using a visual-analogue scale. Electrophysiological and pain parameters of patients during this procedure were compared by means of a linear mixed effect model. Results SCS induced a significant modulation of cortical excitability, especially by influencing the parameter “intracortical facilitation” ( t = −2.657; df = 8; p = 0.029). A significant relationship between this parameter and “perceived pain” could be obtained ( t = −4.798; df = 8; p = 0.002). Conclusions These results suggest that SCS is able to influence neurobiological processes at the supraspinal level and that clinical effects of SCS may be at least in part of cortical origin.

Structural MRI brain analysis and segmentation is a crucial part in the daily routine in neurosurgery for intervention planning. Exemplarily, the free software FSL-FAST (FMRIB’s Segmentation Library – FMRIB’s Automated Segmentation Tool) in version 4 is used for segmentation of brain tissue types. To speed up the segmentation procedure by parallel execution, we transferred FSL-FAST to a General Purpose Graphics Processing Unit (GPGPU) using Open Computing Language (OpenCL) [1]. The necessary steps for parallelization resulted in substantially different and less useful results. Therefore, the underlying methods were revised and adapted yielding computational overhead. Nevertheless, we achieved a speed-up factor of 3.59 from CPU to GPGPU execution, as well providing similar useful or even better results.

ObjectiveRecent studies have investigated the role of spinal image guidance for pedicle screw placement. Many authors have observed an elevated placement accuracy and overall improvement of outcome measures. This study assessed a bi-institutional experience following introduction of the Renaissance miniature robot for spinal image guidance in Europe.MethodsThe medical records and radiographs of all patients who underwent robot-guided implantation of spinal instrumentation using the novel system (between October 2011 and March 2015 in Mainz and February 2014 and February 2016 in Regensburg) were reviewed to determine the efficacy and safety of the newly introduced robotic system. Screw position accuracy, complications, exposure durations to intraoperative radiation, and reoperation rate were assessed.ResultsOf the 413 surgeries that used robotic guidance, 406 were via a minimally invasive approach. In 7 cases the surgeon switched to conventional screw placement, using a midline approach, due to referencing problems. A total of 2067 screws were implanted using robotic guidance, and 1857 screws were evaluated by postoperative CT. Of the 1857 screws, 1799 (96.9%) were classified as having an acceptable or good position, whereas 38 screws (2%) showed deviations of 3–6 mm and 20 screws (1.1%) had deviations > 6 mm. Nine misplaced screws, implanted in 7 patients, required revision surgery, yielding a screw revision rate of 0.48% of the screws and 7 of 406 (1.7%) of the patients. The mean ± SD per-patient intraoperative fluoroscopy exposure was 114.4 (± 72.5) seconds for 5.1 screws on average and any further procedure required. Perioperative and direct postoperative complications included hemorrhage (2 patients, 0.49%) and wound infections necessitating surgical revision (20 patients, 4.9%).ConclusionsThe hexapod miniature robotic device proved to be a safe and robust instrument in all situations, including those in which patients were treated on an emergency basis. Placement accuracy was high; peri- and early postoperative complication rates were found to be lower than rates published in other series of percutaneous screw placement techniques. Intraoperative radiation exposure was found to be comparable to published values for other minimally invasive and conventional approaches.

In many centers the standard anesthesiological care for deep brain stimulation (DBS) surgery in Parkinson's disease patients is an asleep-awake-asleep procedure. However, sedative drugs and anesthetics can compromise ventilation and hemodynamic stability during the operation and some patients develop a delirious mental state after the initial asleep phase. Further, these drugs interfere with the patient's alertness and cooperativeness, the quality of microelectrode recordings, and the recognition of undesired stimulation effects. In this study, we correlated the incidence of intraoperative delirium with the amount of anesthetics used intraoperatively.The anesthesiologic approach is based on continuous presence and care, avoidance of negative suggestions, use of positive suggestions, and utilization of the patient's own resources. Clinical data from the operations were analyzed retrospectively, the occurrence of intraoperative delirium was extracted from patients' charts. The last 16 patients undergoing the standard conscious sedation procedure (group I) were compared to the first 22 (group II) psychologically-guided patients.The median amount of propofol decreased from 146 mg (group I) to 0mg (group II), remifentanyl from 0.70 mg to 0.00 mg, respectively (P0.001 for propofol and remifentanyl). Using the new procedure, 12 of 22 patients (55%) in group II required no anesthetics. Intraoperative delirium was significantly less frequent in group II (P=0.03).The occurrence of intraoperative delirium correlates with the amount of intraoperative sedative and anesthetic drugs. Sedation and powerful analgesia are not prerequisites for patients' comfort during awake-DBS-surgery.

Background During awake craniotomies, patients may either be awake for the entire duration of the surgical intervention (awake-awake-awake craniotomy, AAA) or initially sedated (asleep-awake-asleep craniotomy, SAS). Objective To examine whether prior sedation in SAS may restrict brain mapping, we conducted neuropsychological tests in patients by means of a standardized anesthetic regimen comparable to an SAS. Methods We prospectively examined patients undergoing surgery either under total intravenous anesthesia (TIVA) or under regional anesthesia with slight sedation (RAS). The tests included the DO40 picture-naming test, the digit span, the Regensburg Word Fluency Test, and the finger-tapping test. Each test was conducted 3 times for every patient in the TIVA and RAS groups, once before surgery and twice within about 35 minutes after the end of sedation. Patients undergoing AAA were examined preoperatively and intraoperatively. Results In the AAA group, no significant difference was found between preoperative and intraoperative test results. In the TIVA and RAS groups, postoperative tests showed worse results than preoperative tests. In most tests, patients improved from the first to the second postoperative test. Conclusion Cognitive and motor performance were significantly influenced by prior sedation in the TIVA and RAS groups, but not in the AAA group. Therefore, prior sedation may be assumed to cause a change in the baselines, which may compromise brain mapping and thus endanger a patient's neurological outcome in the case of an SAS.

Objective: The generally used asleep-awake-asleep protocol makes reliable intra-operative testing difficult as patients are frequently disoriented when woken-up from sedation. Furthermore, this protocol carries potential risks for the patient, the most common among them being respiratory complications. In an effort to eliminate potential risks for the patient during awake craniotomies, and in order to improve reliability of intra-operative test results, we implemented a new protocol for awake craniotomies, the continuous awake craniotomy protocol, where the patient is not sedated during the entire procedure. We present first results of this new protocol. Methods: In a prospective study we analyzed awake craniotomies that were performed between September 2006 and June 2008. Data included OR-records, anesthesiological protocols, patient charts, and neuropsychological records. Results: Data of 12 consecutive primary brain tumor patients (six men/six women) with a mean age of 46 years who underwent 13 awake craniotomies were analyzed. A gross total resection was achieved in ten patients (83.3%), of which one patient (8.3%) suffered from a new neurological deficit postoperatively. One patient suffered a generalized seizure and one a focal seizure triggered by direct cortical stimulation. There were no anesthesiological or surgical complications in this study. Conclusion: This study shows that the continuous awake craniotomy protocol is safe, was tolerated well by all patients, and created a very controllable situation during all surgeries. Applying this method, sedation related complications, such as respiratory complications and hemodynamic dysregulation, can be avoided, as are potential risks during an intra-operative wake-up phase. Furthermore, intra-operative neuropsychological test results become more reliable.

Diffusion tensor imaging (DTI)-based tractography has become an integral part of preoperative diagnostic imaging in many neurosurgical centers, and other nonsurgical specialties depend increasingly on DTI tractography as a diagnostic tool. The aim of this study was to analyze the anatomic accuracy of visualized white matter fiber pathways using different, readily available DTI tractography software programs.Magnetic resonance imaging scans of the head of 20 healthy volunteers were acquired using a Siemens Symphony TIM 1.5T scanner and a 12-channel head array coil. The standard settings of the scans in this study were 12 diffusion directions and 5-mm slices. The fornices were chosen as an anatomic structure for the comparative fiber tracking. Identical data sets were loaded into nine different fiber tracking packages that used different algorithms. The nine software packages and algorithms used were NeuroQLab (modified tensor deflection [TEND] algorithm), Sörensen DTI task card (modified streamline tracking technique algorithm), Siemens DTI module (modified fourth-order Runge-Kutta algorithm), six different software packages from Trackvis (interpolated streamline algorithm, modified FACT algorithm, second-order Runge-Kutta algorithm, Q-ball [FACT algorithm], tensorline algorithm, Q-ball [second-order Runge-Kutta algorithm]), DTI Query (modified streamline tracking technique algorithm), Medinria (modified TEND algorithm), Brainvoyager (modified TEND algorithm), DTI Studio modified FACT algorithm, and the BrainLab DTI module based on the modified Runge-Kutta algorithm. Three examiners (a neuroradiologist, a magnetic resonance imaging physicist, and a neurosurgeon) served as examiners. They were double-blinded with respect to the test subject and the fiber tracking software used in the presented images. Each examiner evaluated 301 images. The examiners were instructed to evaluate screenshots from the different programs based on two main criteria: (i) anatomic accuracy of the course of the displayed fibers and (ii) number of fibers displayed outside the anatomic boundaries.The mean overall grade for anatomic accuracy was 2.2 (range, 1.1-3.6) with a standard deviation (SD) of 0.9. The mean overall grade for incorrectly displayed fibers was 2.5 (range, 1.6-3.5) with a SD of 0.6. The mean grade of the overall program ranking was 2.3 with a SD of 0.6. The overall mean grade of the program ranked number one (NeuroQLab) was 1.7 (range, 1.5-2.8). The mean overall grade of the program ranked last (BrainLab iPlan Cranial 2.6 DTI Module) was 3.3 (range, 1.7-4). The difference between the mean grades of these two programs was statistically highly significant (P0.0001). There was no statistically significant difference between the programs ranked 1-3: NeuroQLab, Sörensen DTI Task Card, and Siemens DTI module.The results of this study show that there is a statistically significant difference in the anatomic accuracy of the tested DTI fiber tracking programs. Although incorrectly displayed fibers could lead to wrong conclusions in the neurosciences field, which relies heavily on this noninvasive imaging technique, incorrectly displayed fibers in neurosurgery could lead to surgical decisions potentially harmful for the patient if used without intraoperative cortical stimulation. DTI fiber tracking presents a valuable noninvasive preoperative imaging tool, which requires further validation after important standardization of the acquisition and processing techniques currently available.

There is a discrepancy between the brain regions revealed by functional neuroimaging techniques and those brain regions where a loss of function, either by lesion or by electrocortical stimulation, induces language disorders. To differentiate between essential and non-essential language-related processes, we investigated the effects of linguistic control tasks and different analysis methods for functional MRI data. Twelve subjects solved two linguistic generation tasks: (1) a verb generation task and (2) an antonym generation task (each with a linguistic control task on the phonological level) as well as two decision tasks of semantic congruency (each with a cognitive high-level control task). Differential contrasts and conjunction analyses were carried out on the single-subject level and an individual lateralization index (LI) was computed. On the group level we determined the percent signal change in the left inferior frontal gyrus (IFG: BA 44 and BA 45). The conjunction analysis of multiple language tasks led to significantly greater absolute LIs than the LIs based on the single task versus fixation contrasts. A further significant increase of the magnitude of the LIs could be achieved by using the phonological control conditions. Although the decision tasks appear to be more robust to changes in the statistical threshold, the combined generation tasks had an advantage over the decision tasks both for assessing language dominance and locating Broca's area. These results underline the need for conjunction analysis based on several language tasks to suppress highly task-specific processes. They also point to the need for high-level cognitive control tasks to partial out general, language supporting but not language critical processes. Higher absolute LIs, which reflect unambiguously hemispheric language dominance, can be thus obtained.

Background Despite technical and diagnostic progress there are still open questions in the understanding of the pathophysiology of intracranial aneurysms. Objective Within 44 days we observed the de novo genesis and rupture of an aneurysm of the basilar artery in a patient. We performed computational fluid dynamics on 3-dimensional (3D) models of the inconspicuous vessel and the same vessel with aneurysm. Based on the simulations we propose a mechanism of genesis of fast-growing aneurysms. Methods Three-dimensional mesh models were built using computed tomography-angiography slices. Flow was modeled as a non-Newtonian blood model with shear-dependent dynamic viscosity. We investigated flow velocity, wall pressure, impingement point, wall shear stress (WSS), and asymmetric flows in 3D models of the vessel tree of the basilar artery. Results Impingement point and wall pressure had no clear relation to the origin of the aneurysm. The impingement point faded away during aneurysm growth. Instead we found an area of permanently low WSS in the original basilar artery. This location corresponded to the origin of the later developing aneurysm. Aneurysm growth was facilitated by an increasing overall expansion of the basilar tip and a constant decrease of WSS. Conclusion Assuming a preexisting reduced resistibility of the vessel wall to pressure changes and an area of permanently low WSS, an increase in pressure induces geometrical changes. These cause changes of intravascular flow distribution, lowering the already low WSS in specific locations. This leads to endothelial damage in this area and to a decreasing stability of the vessel wall, causing aneurysm development, growth, and rupture.

OBJECTIVE: Well-documented case reports of the rapid formation and rupture of de novo aneurysms of the posterior circulation are rare. CLINICAL PRESENTATION: We report a patient with subarachnoid hemorrhage caused by an aneurysm of the anterior communicating artery that was clipped consecutively. Forty-four days after the initial subarachnoid hemorrhage, the patient experienced a second subarachnoid hemorrhage after the rupture of a newly grown aneurysm of the basilar tip. Between the two hemorrhages, transcranial Doppler sonography and neuroimaging revealed a fulminant generalized vasospasm. INTERVENTION: To our knowledge, this is the first report of the rapid development and rupture of a de novo aneurysm of the posterior circulation after the rupture of an initial aneurysm of the anterior circulation. CONCLUSION: We review the pertinent literature and discuss possible reasons for the development and rupture of this second aneurysm.

A prospective study is presented on the amount of targeting error that is due to rotational deviations between the atlas and the stereotactic coordinate system.We investigated 14 volunteers with a stereotactic frame fixed to their heads by tight adhesive bands. Sagittal, coronal and axial T2-weighted MRI scans, as well as MPRage sequences, were performed. The anterior and posterior commissures and one additional point on the midline (the septum pellucidum) were determined on the axial T2-weighted images. Bilateral atlas coordinates for the subthalamic nucleus (STN), globus pallidus pars interna (GPi) and nucleus ventralis intermedius (Vim) were transformed to stereotactic frame coordinates, either without correction or by 2-point or 3-point correction. A total of 896 coordinates (x, y, z for the STN, GPi and Vim in both hemispheres) were calculated.Although the mean differences between the two algorithms (0.24 +/- standard deviation of 0.33 mm) were within the range of system-immanent inaccuracies in MRI-guided stereotaxy, deviations of up to 2.8 mm occurred. No significant correlation was found regarding the amount of rotational angle and the differences in x-, y-, or z-coordinates when 2-point and 3-point transformations were compared.The reliability of meticulous trajectory planning might be compromised significantly by using only 2-point-based correction or no calculations at all.