Health-related quality of life in patients with peripheral nerve tumors: results from the German multicentric Peripheral Nerve Tumor Registry.

Objective: Peripheral nerve tumors (PNTs) are rare diseases. So far, no multicenter data on diagnostics, the efficacy of treatment, long-term outcomes, and health-related quality of life (HRQoL) exist. The establishment of the Peripheral Nerve Tumor Registry (PNTR) in 2015 allows for the systematic analysis of patients with tumors associated with peripheral nerves. The present study aims to investigate the impact of PNT on an individual's HRQoL and the effect of surgery. Methods: HRQoL was pre- and postoperatively assessed by the Euro-Qol-5D-5L (EQ-5D-5L) and Euro-Qol visual analog scale (EQ-VAS) survey in the retrospective and prospective study arm in three active participating study centers. An index was calculated based on the EQ-5D-5L for the quantification of health state (0: worst possible state of health, 1: best possible state of health). The EQ-VAS ranges from 0% (worst imaginable health status) to 100% (best possible health status). Patient characteristics (age, sex), as well as disease (histopathological entity) and treatment (pre- and postoperative symptoms, type of treatment)-specific data, were analyzed. Results: Data from 171 patients from three high-volume centers were included, with schwannoma (70.8%, n = 121) and neurofibroma (15.8%, n = 27) being the most prevalent histopathological diagnoses. Both the median health index value (preoperative: 0.887, n = 167; postoperative: 0.910, n = 166) and the median EQ-VAS (preoperative: 75%, n = 167; postoperative: 85%, n = 166) of the entire cohort regarding all histopathological diagnosis improved significantly after surgical therapy (p < 0.001). Preoperatively, 12.3% (n = 21) reached the highest index score of 1.0 in EQ-5D-5L and 100% in the EQ-VAS score in 5.3% (n = 9) of all patients. Postoperatively, the highest index score of 1.0 and 100% in the EQ-VAS score increased significantly and were achieved in 33.3% (n = 57) and 11.1% (n = 19) of the patients, respectively (p < 0.001). Conclusion: For the first time, our study presents multicenter data on life quality and the effect of surgery in primarily benign peripheral nerve tumors. Early surgery at a specialized center could improve neurological outcomes and, in conclusion, better QoL. In summary, surgical therapy significantly improved the entire cohort's QoL, VAS, and analgesia.

Case report: Atypical neurofibromatous neoplasm with uncertain biological potential of the sciatic nerve and a widespread arteriovenous fistula mimicking a malignant peripheral nerve tumor in a young patient with neurofibromatosis type 1.

We report an unusual constellation of diseases in a 32-year-old woman with neurofibromatosis type 1 (NF1) diagnosed with the recently described precursor entity of malignant peripheral nerve sheath tumor (MPNST), the so-called atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) and a large symptomatic cervical arteriovenous fistula. An [18F] 2-Fluoro-2-deoxy-D-glucose PET/CT (FDG-PET/CT) was performed to detect and stage a conspicuous symptomatic cervical tumor. The FDG-PET/CT showed high FDG uptake in one of the multiple known tumorous lesions associated with peripheral nerves. However, no relevant FDP uptake was observed in this affected cervical area. After digital subtraction angiography, the cervical mass turned out to be a widespread arteriovenous fistula of the vertebral artery. This was successfully treated using endovascular embolization. Subsequently, magnet resonance imaging (MRI) of the FDG-positive tumor revealed a well-enhanced homogeneous mass of the sciatic nerve measuring 5.2×2.4×2.8 cm. Microsurgical gross total tumor resection was performed using ultrasound. The final histopathological diagnosis was ANNUBP transformed from neurofibroma. The patient benefited excellently from the surgery; no recurrence or metastasis has been observed since resection. According to imaging, ANNUBP can be characterized as a well-enhanced homogeneous mass on MRI, displaying high uptake on FDG-PET/CT and hypoechogenic in ultrasound.

Restoring musculocutaneous nerve function in 146 brachial plexus operations - A retrospective analysis.

INTRODUCTION: A brachial plexus lesion is a devastating injury often affecting young, male adults after traffic accidents. Therefore, surgical restoration of elbow flexion is critical for establishing antigravity movement of the upper extremity. We analyzed different methods for musculocutaneous reconstruction regarding outcome. METHODS: We conducted a retrospective analysis of 146 brachial plexus surgeries with musculocutaneous reconstruction performed at our department from 2013 to 2017. Demographic data, surgical method, donor and graft nerve characteristics, body mass index (BMI) as well as functional outcome of biceps muscle based on medical research council (MRC) strength grades before and after surgery were analyzed. Multivariate analysis was performed using SPSS. RESULTS: Oberlin reconstruction was the procedure performed most often (34.2%, n = 50). Nerve transfer and autologous repair showed no significant differences regarding outcome (p = 0.599, OR 0.644 CI95% 0.126-3.307). In case of nerve transfers, we found no significant difference whether reconstruction was performed with or without a nerve graft (e.g. sural nerve) (p = 0.277, OR 0.619 CI95% 0.261-1.469). Multivariate analysis identifies patient age as a strong predictor for outcome, univariate analysis indicates that nerve graft length > 15 cm and BMI of > 25 could lead to inferior outcome. When patients with early recovery (n = 19) are included into final evaluation after 24 months, the general success rate of reconstructions is 62,7% (52/83). CONCLUSION: Reconstruction of musculocutaneous nerve after brachial plexus injury results in a high rate of clinical improvement. Nerve transfer and autologous reconstruction both show similar results. Young age was confirmed as an independent predictor for better clinical outcome. Prospective multicenter studies are needed to further clarify.

Rationale and design of the peripheral nerve tumor registry: an observational cohort study.

AIM: Peripheral nerve tumors (PNT) are rare lesions. To date, no systematic multicenter studies on epidemiology, clinical symptoms, treatment strategies and outcomes, genetic and histopathologic features, as well as imaging characteristics of PNT were published. The main goal of our PNT Registry is the systematic multicenter investigation to improve our understanding of PNT and to assist future interventional studies in establishing hypotheses, determining potential endpoints, and assessing treatment efficacy. METHODS: Aims of the PNT registry were set at the 2015 Meeting of the Section of Peripheral Nerve Surgery of the German Society of Neurosurgery. A study protocol was developed by specialists in PNT care. A minimal data set on clinical status, treatment types and outcomes is reported by each participating center at initial contact with the patient and after 1 year, 2 years, and 5 years. Since the study is coordinated by the Charité Berlin, the PNR Registry was approved by the Charité ethics committee (EA4/058/17) and registered with the German Trials Registry (www.drks.de). On a national level, patient inclusion began in June 2016. The registry was rolled out across Europe at the 2019 meeting of the European Association of Neurosurgery in Dublin. RESULTS: Patient recruitment has been initiated at 10 centers throughout Europe and 14 additional centers are currently applying for local ethics approval. CONCLUSION: To date, the PNT registry has grown into an international study group with regular scientific and clinical exchange awaiting the first results of the retrospective study arm.

The value of intraoperative angiography in the time of indocyanine green videoangiography in the treatment of cerebrovascular lesions: Efficacy, workflow, risk-benefit and cost analysis A prospective study.

INTRODUCTION: Intraoperative digital subtraction angiography (ioDSA) allows early treatment evaluation after neurovascular procedures. However, the value and efficiency of this procedure has been discussed controversially. We have evaluated the additional value of hybrid operating room equipped with an Artis Zeego robotic c-arm regarding cost, efficiency and workflow. Furthermore, we have performed a risk-benefit analysis and compared it with indocyanine green (ICG) angiography. METHODS: For 3 consecutive years, we examined all neurovascular patients, treated in the hybrid operating theater in a risk-benefit analysis. After using microdoppler and ICG angiography for best operative result, every patient received an additional ioDSA to look for remnants or unfavorable clip placement which might lead to a change of operating strategy or results. Furthermore, a workflow-analysis reviewing operating steps, staff positioning, costs, technical errors or complications were conducted on randomly selected cases. RESULTS: 54 patients were enrolled in the risk-benefit analysis, 22 in the workflow analysis. The average duration of a cerebrovascular operation was 4 h 58 min 2 min 35 s accounted for ICG angiography, 46 min 4 s for ioDSA. Adverse events occurred during one ioDSA. In risk-benefit analysis, ioDSA was able to detect a perfusion rest in 2 out of 43 cases (4,7%) of aneurysm surgery, which could not have been visualized by ICG angiography before. In arterio-venous-malformation (AVM) surgery, one of 11 examined patients (7,7%) showed a remnant in ioDSA and resulted in additional resection. The average cost of an ioDSA in Ulm University can be estimated with 1928,00€. CONCLUSION: According to our results ioDSA associated complications are low. Relevant findings in ioDSA can potentially avoid additional intervention, however, due to the high costs and lower availability, the main advantage might lie in the treatment of selected patients with complexes neurovascular pathologies since ICG angiography is equally safe but associated with lower costs and better availability.

Multicentric Registry Study on Epidemiological and Biological Disease Profile as Well as Clinical Outcome in Patients with Low-Grade Gliomas: The LoG-Glio Project.

BACKGROUND: World Health Organization (WHO) grade II low-grade gliomas (LGGs) in adults are rare, and patients' mean overall survival (OS) is relatively long. Epidemiological data on factors influencing tumor genesis and progression are scarce, and prospective data on surgical management are still lacking. Because of the molecular heterogeneity of LGG, a comprehensive molecular characterization is required for any clinical and epidemiological research. Further, a detailed radiologic assessment is needed as the only established objective criterion for progressive disease. Both radiologic and molecular assessments have to be standardized to produce comparable data. The aim of the registry is to improve the evidence for surgical management of LGG patients by establishing a multicenter registry with a strong surgical and clinical focus including mandatory biobanking. METHODS: The LoG-Glio project is a prospective national observational multicenter registry that began on November 1, 2015. Inclusion criteria encompass all patients > 18 years of age with a radiologic suspicion of LGG. Patients with severe neurologic or psychiatric disorders that may interfere with their informed consent or if there is no possibility for further follow-up are excluded. Diagnosis of glioblastoma WHO grade IV isocitrate dehydrogenase (IDH) wild type leads to a secondary exclusion of patients. In addition to demographic data, results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, add-on for patients with brain tumors, and National Health Institute Stroke Scale before and after surgery and during regular follow-ups are collected. At each time point a detailed recording of surgical and adjuvant treatment is performed. Radiologic assessment involves three-dimensional (3D) acquisition of T1, fluid-attenuated inversion recovery, and T2 sequences. For the final evaluation, a central detailed neuropathologic and molecular assessment of tumor samples and a radiologic evaluation of imaging sets are part of the study protocol. RESULTS: We report the first 100 consecutively registered patients for LoG-Glio. Three patients dropped out due to loss of follow-up. Of the remaining recruited patients, 8 were classified as wait and scan; 89 had surgery. Using the inclusion criteria described previously, 70 patients had an IDH-mutated glioma, 10 had miscellaneous rare LGGs, and 8 patients had an IDH wild-type WHO grade II or III glioma. CONCLUSION: The LoG-Glio registry has been successfully implemented. Applied selection criteria result in an appropriately balanced patient cohort. Short-term outcome data on epidemiology as well as the influence of current surgical techniques and adjuvant treatment on patient outcomes are expected. In the long run, the aim of the registry is to validate the new molecular-based WHO classification and the influence of the extent of resection on progression-free survival and OS. The registry provides an open platform for future research projects benefiting patients with LGG. TRIAL REGISTRATION: NCT02686229 Clinical trials.

Clinical outcome after decompression of intraneural peroneal ganglion cyst and its morphologic correlation to postoperative nerve ultrasound.

OBJECTIVE: Intraneural ganglion cysts are rare and benign mucinous lesions that affect peripheral nerves, most frequently the common peroneal nerve (CPN). The precise pathophysiological mechanisms of intraneural ganglion cyst development remain unclear. A well-established theory suggests the spread of mucinous fluid along the articular branch of the peroneal nerve as the underlying mechanism. Clinical outcome following decompression of intraneural ganglion cysts has been demonstrated to be excellent. The aim of this study was to evaluate the correlation between clinical outcome and ultrasound-detected morphological nerve features following decompression of intraneural ganglion cysts of the CPN. METHODS: Data were retrospectively analyzed from 20 patients who underwent common peroneal nerve ganglion cyst decompression surgery at the Universität Ulm/Günzburg Neurosurgery Department between October 2003 and October 2017. Postoperative clinical outcome was evaluated by assessment of the muscular strength of the anterior tibial muscle, the extensor hallucis longus muscle, and the peroneus muscle according to the Medical Research Council grading system. Hypesthesia was measured by sensation testing. In all patients, postoperative morphological assessment of the peroneal nerve was conducted between October 2016 and October 2017 using the iU22 Philips Medical ultrasound system at the last routine follow-up appointment. Finally, the correlations between morphological changes in nerve ultrasound and postoperative clinical outcomes were evaluated. RESULTS: During the postoperative ultrasound scan an intraneural hypoechogenic ring structure located at the medial side of the peroneal nerve was detected in 15 (75%) of 20 patients, 14 of whom demonstrated an improvement in motor function. A regular intraneural fasicular structure was identified in 3 patients (15%), who also reported recovery. In 1 patient, a recurrent cyst was detected, and 1 patient showed intraneural fibrosis for which recovery did not occur in the year following the procedure. Two patients (10%) developed neuropathic pain that could not be explained by nerve ultrasound findings. CONCLUSIONS: The results of this study demonstrate significant recovery from preoperative weakness after decompression of intraneural ganglion cysts of the CPN. A favorable clinical outcome was highly correlated with an intraneural hypoechogenic ring-shaped structure on the medial side of the CPN identified during a follow-up postoperative ultrasound scan. These study results indicate the potential benefit of ultrasound scanning as a prognostic tool following decompression procedures for intraneural ganglion cysts of the CPN.

The influence of nimodipine and vasopressors on outcome in patients with delayed cerebral ischemia after spontaneous subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a major factor contributing to the inferior outcome of patients with spontaneous subarachnoid hemorrhage (SAH). Nimodipine and induced hypertension using vasopressors are an integral part of standard therapy. Consequences of the opposite effect of nimodipine and vasopressors on blood pressure on patient outcome remain unclear. The authors report the detailed general characteristics and influence of nimodipine and vasopressors on outcome in patients with SAH. METHODS: The authors performed a 2-center, retrospective, clinical database analysis of 732 SAH patients treated between 2008 and 2016. Demographic and clinical data such as age, sex, World Federation of Neurosurgical Societies (WFNS) grade, BMI, Fisher grade, history of arterial hypertension and smoking, aneurysm location, C-reactive protein (CRP) level, and detailed dosage of vasopressors and nimodipine during the treatment period were evaluated. Clinical outcome was analyzed using the modified Rankin Scale (mRS) 6 months after treatment. Univariate and multivariate regression analyses were performed. Additionally, mean arterial pressure (MAP), age, nimodipine, and vasopressor dose cutoff were evaluated with regard to outcome. The level of significance was set at ≤ 0.05. RESULTS: Follow-up was assessed for 397 patients, 260 (65.5%) of whom achieved a good outcome (defined as an mRS score of 0-3). Univariate and multivariate analyses confirmed that nimodipine (p = 0.049), age (p = 0.049), and CRP level (p = 0.002) are independent predictors of good outcome. WFNS grade, Fisher score, hypertension, initial hydrocephalus, and total vasopressor dose showed significant influence on outcome in univariate analysis, and patient sex, smoking status, BMI, and MAP showed no significant association with outcome. A subgroup analysis of patients with milder initial SAH (WFNS grades I-III) revealed that initial hydrocephalus (p = 0.003) and CRP levels (p = 0.001) had significant influence on further outcome. When evaluating only patients with WFNS grade IV or V, age, CRP level (p = 0.011), vasopressor dose (p = 0.030), and nimodipine dose (p = 0.049) were independent predictors of patient outcome. Patients with an MAP < 93 mm Hg, a nimodipine cutoff dose of 241.8 mg, and cutoff total vasopressor dose of 523 mg had better outcomes. CONCLUSIONS: According to the authors' results, higher doses of vasopressors can safely provide a situation in which the maximum dose of nimodipine could be administered. Cutoff values of the total vasopressor dose were more than 3 times higher in patients with severe SAH (WFNS grade IV or V), while the nimodipine cutoff remained similar in patients with mild and severe SAH. Hence, it seems encouraging that a maximum nimodipine dosage can be achieved despite the need for a higher vasopressor dose in patients with SAH.

Diagnostic accuracy of intraoperative perfusion-weighted MRI and 5-aminolevulinic acid in relation to contrast-enhanced intraoperative MRI and 11C-methionine positron emission tomography in resection of glioblastoma: a prospective study.

The aim of our study was to compare depicted pre-, intra-, and postoperative tumor volume of met-PET, perfusion-weighed MRI (PWI), and Gd-DTPA MRI. Further, to assess their sensitivity and specificity in correlation with histopathological specimen. Inclusion criteria of the prospective study were histological confirmed glioblastoma (GB), age > 18, and eligible for gross total resection (GTR). Met-PET was performed before and after surgery. Gd-DTPA MRI and PWI were performed before, during, and after surgery. A combined 5-aminolevulinic acid (5-ALA) and iMRI-guided surgery was performed. Volumetric analysis was evaluated for all imaging modalities except for 5-ALA. A total of 59 navigated biopsies were taken. Sensitivity and specificity were calculated for Gd-DTPA MRI, PWI, met-PET, and 5-ALA according to the histology of specimen. Met-PET depicted significantly larger tumor volume before surgery (p = 0.01) compared to PWI and Gd-DTPI MRI. We found no significant difference in tumor volume between met-PET and PWI after surgery (p = 0.059). Both PWI and met-PET showed significantly larger tumor volume after surgery when compared to Gd-DTPA (p = 0.018 and p = 0.003, respectively). Intraoperative PWI reading was impaired in 33.3% due to artifacts. Met-PET showed the highest sensitivity for detection of GB with 95%. The lowest sensitivity was found with Gd-DTPA MRI (50%), while 5-ALA and intraoperative PWI showed similar results (69 and 67%). Met-Pet is the imaging modality with the highest sensitivity to detect a residual tumor in GB. Intraoperative PWI seems to have a synergistic effect to Gd-DTPA and 5-ALA. However, its value may be limited by artifacts. Both pre- and intraoperative PWI cannot substitute met-PET in tumor detection.

Quality of Life After Treatment of Unruptured Intracranial Aneurysms.

OBJECTIVE: Quality of life is an important factor in the decision making for the treatment of unruptured intracranial aneurysms (UIA). The data dealing with QoL in patients after the treatment are spare. We have evaluated QoL of patients after endovascular or surgical treatment of incidental intracranial aneurysm. METHODS: We performed a prospective analysis of retrospectively collected data. All patients received 36-Item Short Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), German questionnaire for self-perceived deficits in attention (FEDA) and not standardized questionnaire analyzing personal job-related situation, family circumstances and chronic illnesses. RESULTS: 177 patients were treated during the evaluated period. 79 (44.6%) patients responded. In this cohort, 62.03% of patients underwent coiling. Complications were noted in 13.9% of patients. Stroke was the most common complication (7.6%). All SF-36 related data except for pain showed significant lower mean, if compared to the standard German population (p < 0.01). For both genders, anxiety (males, P = 0.003 and females, P = 0.002) but not depression was more common than in the standard population. According to the FEDA test, treated patients showed significant difference only for fatigue in comparison to healthy population (P < 0.001). 54.4% of patients suffered from chronic illnesses, and among them only 1 patient (1.3%) had aneurysm associated chronic disease. No significant differences were found between treatment modalities. CONCLUSIONS: The risk for depression and pain is not significantly increased after elective treatment of UIA. According to our results, decreased QoL is common in this cohort of patients but often related to factors not associated with aneurysm treatment.

Clipping as re-treatment strategy after treatment of a cerebral aneurysm with the Woven EndoBridge embolization device: case report.

Recently, treatment of cerebral aneurysms with the Woven EndoBridge (WEB) device has become an established endovascular strategy. However, over time, neurosurgeons and neuroradiologists will be confronted with the challenge of how to treat aneurysm recanalization. The authors report the case of a 49-year-old woman who underwent re-treatment with clipping after the recanalization of a 4 × 3-mm anterior communicating artery aneurysm that had previously been treated using a 4 × 3 WEB device. In contrast to the authors' prior experiences with clipping of previously coiled aneurysms, the WEB device was found to have a responsive softness during clip placement, and the aneurysm was more maneuverable. Moreover, evaluation with indocyanine green angiography was easy to perform because of the transparent mesh of the WEB device. No profound scarring or WEB protrusion was noted during surgery, making the procedure easier and less dangerous with regard to additional complications. The authors suggest that re-treatment via clipping should be considered in select cases of aneurysm recurrence after treatment with an intraaneurysmal flow diverter.

Is MGMT promoter methylation to be considered in the decision making for recurrent surgery in glioblastoma patients?

OBJECTIVES: At present, there is no standard therapy approved for recurrent glioblastoma (rGB). In particular, the counselling of patients with an unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter GB remains a challenge. Our aim was to compare the overall survival (OS) and progression free survival (PFS) in patients treated surgically and non-surgically at the time of GB recurrence. This was evaluated with particular reference to the impact of recurrent surgery for patients with unmethylated MGMT promoter rGB. PATIENTS AND METHODS: The clinical and radiological data from 127 consecutive cases of rGB was retrospectively identified and evaluated. The PFS and OS from cohorts of surgically and non-surgically treated patients at time of GB recurrence were compared using Kaplan Meier estimations and Log-Rank tests. Multivariate Cox regression analysis included the major influencing variables (surgical resection, MGMT promoter methylation status, Karnofsky performance scale (KPS), age, eloquent tumor location) to analyze the survival benefit. Subgroup analysis of cases depending on the MGMT promoter methylation status was performed. RESULTS: Multiple Cox regression analysis revealed inferior OS (p = 0.029, OR = 1.731, CI 95% 1.059-2.829) of patients treated non-surgically (14 vs. 31 months). MGMT promoter methylation and age were related to longer OS (p < 0.001, OR 2.683, CI 95% 1.631-4.414 and p = 0.009, OR = 1.029, CI95% 1.007-0.052 respectively). Gross total resection (GTR) in comparison to subtotal resection (STR) lead to a median OS of 39 months vs. 22 months and a PFS of seven vs. four months respectively. In the subgroup of cases with unmethylated MGMT promoter rGB, those who underwent GTR survived significantly longer (OS: 31 months) than patients who underwent STR (OS: 15 months, p = 0.024). PFS was six vs. four months after GTR and STR respectively. CONCLUSION: Surgical management for recurrent glioblastoma appears to be a safe procedure which results in longer OS in comparison to non-surgical management. GTR may be of particular benefit to patients with unmethylated MGMT promoter rGB.

Experimental study of sector and linear array ultrasound accuracy and the influence of navigated 3D-reconstruction as compared to MRI in a brain tumor model.

PURPOSE: Currently, intraoperative ultrasound in brain tumor surgery is a rapidly propagating option in imaging technology. We examined the accuracy and resolution limits of different ultrasound probes and the influence of 3D-reconstruction in a phantom and compared these results to MRI in an intraoperative setting (iMRI). METHODS: An agarose gel phantom with predefined gel targets was examined with iMRI, a sector (SUS) and a linear (LUS) array probe with two-dimensional images. Additionally, 3D-reconstructed sweeps in perpendicular directions were made of every target with both probes, resulting in 392 measurements. Statistical calculations were performed, and comparative boxplots were generated. RESULTS: Every measurement of iMRI and LUS was more precise than SUS, while there was no apparent difference in height of iMRI and 3D-reconstructed LUS. Measurements with 3D-reconstructed LUS were always more accurate than in 2D-LUS, while 3D-reconstruction of SUS showed nearly no differences to 2D-SUS in some measurements. We found correlations of 3D-reconstructed SUS and LUS length and width measurements with 2D results in the same image orientation. CONCLUSIONS: LUS provides an accuracy and resolution comparable to iMRI, while SUS is less exact than LUS and iMRI. 3D-reconstruction showed the potential to distinctly improve accuracy and resolution of ultrasound images, although there is a strong correlation with the sweep direction during data acquisition.

Contemporary use of intraoperative imaging in glioma surgery: A survey among EANS members.

OBJECTIVES: In glioma surgery, intraoperative imaging is regarded highly valuable to improve extent of resection. Current distribution of intraoperative imaging techniques is largely unknown. Further, controversy exists which method might be most beneficial. PATIENTS AND METHODS: We performed a web-based survey among members of the European Association of Neurological Surgeons(EANS) from April to May 2017. Our questionnaire included intraoperative MRI(iMRI), 5-aminolevulinic acid(5-ALA), intraoperative ultrasound(iUS),Na-Fluorescein and intraoperative CT(iCT). The value of each method in resection of glioblastoma(GB) and low-grade-glioma(LGG) and their role for intraoperative orientation and usability were rated based on Likert-scales from 1(not valuable/important) to 5(very valuable/important). A total score was calculated based on each sub-score. Mann-Whitney-U-test was used to compare ratings of imaging methods. RESULTS: Among the 310 participants, iMRI and 5-ALA were regarded as the most valuable intraoperative imaging methods in GB-surgery (iMRIvs.5-ALA,p=0.573;mean 4.05(SE0.149)vs.4.22(SE0.216)). Both were considered significantly more valuable than iUS, Na-Fluorescein and iCT(p≤0.001).Compared to all other methods, iMRI received significantly higher ratings for the resection of LGGs (p<0.01,mean 4.21(SE 0.143)) as well as for intraoperative orientation (mean 4.00(SE0.166)).5-ALA was rated highest regarding intraoperative usability (mean 4.07(SE0.082)). iMRI showed the highest total score compared to all other imaging modalities(p<0.001,mean 15.95(SE 0.484)). CONCLUSION: iMRI and 5-ALA were rated most valuable for GB-surgery, while only iMRI reached higher ratings in LGG cases. iMRI was the best imaging method for intraoperative orientation as well as the most valuable method in overall rating. Considering the total score, 5-ALA and iUS received similar values and were rated second highest, followed by Na-Fluorescein and iCT.

Mechanisms, Treatment, and Patient Outcome of Iatrogenic Injury to the Brachial Plexus-A Retrospective Single-Center Study.

BACKGROUND: Injury to the brachial plexus is a devastating condition, with severe impairment of upper extremity function resulting in distinct disability. There are no systematic reports on epidemiology, causative mechanisms, treatment strategies. or outcomes of iatrogenic brachial plexus injury (iBPI). METHODS: We screened all cases of iatrogenic nerve injuries recorded between 2007 and 2017 at a single specialized institution. Mechanism of iBPI, type of previous causative intervention, location and type of the lesion as well as the type of revision surgery and functional patient outcome were analyzed. RESULTS: We identified 14 cases of iBPI, which all presented with significant impairment of upper extremity motor function (at least 1 muscle Medical Research Council grade 0). Neuropathic pain was present in most patients (11/14). Orthopedic shoulder procedures such as rotator cuff fixation, arthroplasty, and repositioning of a clavicle fracture accounted for iBPI in 7 of 14 patients. Other reasons for iBPI were resection or biopsy of a peripheral nerve sheath tumor in 3 patients or lymph node situated at the cervicomediastinal area in 2 patients. Mechanisms also included transaxillary rib resection in one and sternotomy in another patient. The treatment of iBPI was conducted according to each individual's needs and included neurolysis in 4, nerve grafting in 9, and nerve transfers in 1 patient. We found improved symptoms after treatment in most patients (11/14). CONCLUSIONS: Most common causes for iBPI were shoulder surgery and resection or biopsy of peripheral nerve sheath tumor and lymph nodes. Early referral to specialized peripheral nerve centers may help to improve functional patient outcome.

Activation of Cytotoxic Natural Killer Cells After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Cell-mediated inflammation is critical in the development of cerebrovascular complications after aneurysmal subarachnoid hemorrhage. We analyzed the course for activated CD16brightCD56dim cytotoxic natural killer (NK) cells in cerebrospinal fluid of 15 patients. METHODS: Patients were classified by occurrence of cerebral vasospasm (CV) and delayed cerebral ischemia. NK were monitored by flow cytometry between day 1 and 14 after hemorrhage. RESULTS: Twelve patients (80%) developed CV with a mean day of detection at 3.9 ± 1.6. In those patients, cell count for NK increased from 1.40 ± 1.42 cells/µL on day 1 to a peak of 11.66 ± 11.56 cells/µL on day 6.1 ± 2.9 (P = 0.001). An increase of mean cerebral blood flow velocity in transcranial Doppler from 71.33 ± 12.93 cm/second to 166.20 ± 20.19 cm/second (P < 0.01) and an increase in number of vascular axes affected by CV was detected (P < 0.01). In patients with grade 3 CV (n = 4, 33.3%), activated NK counts were significantly higher than in patients who did not have CV (23.18 ± 13.92 cells/µL vs. 0.02 ± 0.01 cells/µL; P = 0.029). NK counts were significantly different between patients with grade 1 and grade 3 CV (P = 0.04). Patients who did not have CV who showed low NK counts achieved better functional outcome (Glasgow Outcome Scale [GOS] score, 4.6 ± 0.6) at discharge than did patients with CV grade 2 (GOS score, 3.3 ± 0.5) and CV grade 3 (GOS score, 2.3 ± 0.5) who showed increased NK cell counts (CV grade 0 vs. CV grade 2, P = 0.048; CV grade 0 vs. CV grade 3, P = 0.001). Activated CD16brightCD56dim cytotoxic NKCSF cell counts showed a mean maximum (14.15 ± 12.21 cells/µL) when delayed cerebral ischemia occurred. CONCLUSIONS: The increase of activated CD16brightCD56dim cytotoxic NK cells in cerebrospinal fluid after aneurysmal subarachnoid hemorrhage suggests an increased risk of CV and delayed cerebral ischemia.

Histopathological Insights on Imaging Results of Intraoperative Magnetic Resonance Imaging, 5-Aminolevulinic Acid, and Intraoperative Ultrasound in Glioblastoma Surgery.

BACKGROUND: For appropriate use of available intraoperative imaging techniques in glioblastoma (GB) surgery, it is crucial to know the potential of the respective techniques in tumor detection. OBJECTIVE: To assess histopathological basis of imaging results of intraoperative magnetic resonance imaging (iMRI), 5-aminolevulinic acid (5-ALA), and linear array intraoperative ultrasound (lioUS). METHODS: We prospectively compared the imaging findings of iMRI, 5-ALA, and lioUS at 99 intraoperative biopsy sites in 33 GB patients during resection control. Histological classification of specimens, tumor load, presence of necrosis, presence of vascular malformations, and O6-methylguanin-DNA methyltransferase (MGMT) promoter state was correlated with imaging findings. RESULTS: Solid tumor was found in 57%, infiltration zone in 42%, and no tumor in 1% of specimens. However, imaging was negative in iMRI in 49%, using 5-ALA in 17%, and in lioUS in 21%. In positive imaging results, share of solid tumor was highest in 5-ALA (65%) followed by lioUS (60%) and lowest in iMRI (55%). In comparison to 5-ALA, iMRI had a high share of solid tumor in specimens when showing intermediate results. Sensitivity for invasive tumor was higher in 5-ALA (84%) and lioUS (80%) than in iMRI (50%). We found a significant correlation of 5-ALA with classification of specimen, presence of necrosis, and microproliferations. Methylated MGMT promoter correlated with positive findings in 5-ALA. lioUS and iMRI showed no correlations with histopathological findings. CONCLUSION: All of the assessed established imaging techniques detect infiltrating tumor only to a certain extent. Only 5-ALA showed a significant correlation with histopathological findings. Interestingly, tumor remnants in an MGMT-methylated tumor are more likely to be visible using 5-ALA as in unmethylated tumors.

Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging.

BACKGROUND: In patients with a glioblastoma (GBM), few unselected data exists using actual standard adjuvant treatment and contemporary surgical techniques like iMRI. Aim of study is to assess impact of EoR and recurrent surgery on survival and outcome. METHODS: We assessed a consecutive unselected series of 170 surgeries for GBM (2008-2014) applying intraoperative MRI (iMRI). All patients received adjuvant radio-chemo-therapy. Overall-survival (OS), progression free survival (PFS), complications and new permanent neurological deficits (nPND) were assessed. Uni- and multivariate-cox-regression-models were calculated. RESULTS: Mean follow-up was 40mo. GTR was intended in 82% and achieved in 77% of these cases. A nPND was found in 7% of patients. In multivariate cox-regression, GTR (HR:0.6, P<0.024) and absence of MGMT methylation (HR:1.6, P<0.042) was significantly associated with PFS. We found no difference in PFS after primary surgery and recurrent surgery. Concerning OS, in multivariate assessment an un-methylated MGMT-promotor (HR2.0, P<0.01) and presence of a complication (HR1.7, P<0.06) were negative prognosticators. Only GTR was significantly beneficial for OS (HR0.4, P<0.028) compared to a failed GTR and a STR. Repeated surgery for recurrent disease was positively associated with OS (HR0.6, P<0.06). CONCLUSIONS: Surgery in a contemporary setup using iMRI, brain mapping and modern adjuvant treatment, has a higher OS and lower complication rates as previously published. A maximum but safe resection should be the goal of surgery since a perioperative complication significantly decreases OS. Recurrent surgery has a beneficial effect on OS without an increase of complications.

The Value of Intraoperative and Early Postoperative Magnetic Resonance Imaging in Low-Grade Glioma Surgery: A Retrospective Study.

BACKGROUND: The presence of residual tumor is crucial in decision-making for low-grade gliomas (LGGs), because patients older than 40 years of age with residual tumor are considered for adjuvant treatment. There are hints that early postoperative fluid-attenuated inversion recovery (FLAIR) and T2 (within 48 hours) may overestimate residual tumor volume in LGG. Intraoperative magnetic resonance imaging (MRI) without subsequent resection or ultra-early postoperative MRI may assess the amount of residual tumor more adequately. To evaluate the utility of postoperative imaging in LGG, we volumetrically analyzed intraoperative, early, and late (3-4 months after surgery) postoperative MRIs of LGGs. PATIENTS AND METHODS: A total of 33 patients with LGG were assessed retrospectively. Residual tumor was defined as signal-enhanced tissue in T2 and FLAIR. Volumetric assessment was performed with intraoperative, early, and late postoperative T2/FLAIR via Brainlab-iPlan 3.0. Wilcoxon and χ(2) tests were used for statistical analysis. RESULTS: A significant difference of FLAIR/T2 abnormalities was found in intraoperative and early postoperative MRIs (FLAIR mean volume = 5.433 cm(3), T2 mean volume = 3.374 cm(3) vs. FLAIR mean volume = 14.090 cm(3), P = 0.002, T2 mean volume = 7.597 cm(3), P = 0.006). There was no significant difference between intraoperative and late postoperative FLAIR/T2 abnormalities (late postoperative FLAIR/T2 mean volume = 5.560 cm(3) and 2.370 cm(3), P = 0.520, P = 0.398), whereas a significant difference was detected between early and late postoperative images (FLAIR, P < 0.0001; T2, P < 0.00001). CONCLUSION: Intraoperative MRI without further resection or ultra-early postoperative MRI seems to reflect the actual volume of residual tumor in LGG more precisely compared with early postoperative MRI and therefore seems to be more useful regarding decisions for adjuvant therapy.