Diffuse Leptomeningeal Glioneuronal Tumor in Adults: Case Report and Literature Review.

Introduction: Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting with disseminated leptomeningeal enhancement and an occasional intraparenchymal mass. Diagnosis is often impeded by infectious/immunological differentials, necessitating a biopsy to confirm the diagnosis. We report an adult male with DLGNT without hydrocephalus, which is rare in patients with cerebellar masses. Case Presentation: A 56-year-old man presented with headaches, vertigo, diplopia, impaired hearing, and gait imbalance over 6 months. Magnetic resonance imaging showed a cystic right cerebellar mass with its leptomeningeal dissemination but without hydrocephalus. Cerebrospinal fluid analysis revealed elevated proteins with CD56-positive tumor cells. Cerebellar lesion biopsy verified the diagnosis of DLGNT (WHO Grade 3) with KIAA1549::BRAF fusion and 1p deletion. Radiotherapy was prematurely aborted due to clinical deterioration. The patient was subsequently discharged to palliative home care and lost to follow-up. Conclusion: We conducted the first review of all 34 adult DLGNT cases, including ours (one of the oldest), hitherto published in the literature. The majority presented with signs and symptoms of increased intracranial pressure. 52.0% of adult DLGNT patients were alive at follow-up. DLGNT should be considered in the differential diagnoses of diffuse leptomeningeal enhancement in imaging. Further studies comparing pediatric and adult subgroups of DLGNT are needed to evaluate histopathological prognosticators and standardize therapy for both subpopulations.

Changes in frailty among patients hospitalized for spine pathologies during the COVID-19 pandemic in Germany-a nationwide observational study.

PURPOSE: In spine care, frailty is associated with poor outcomes. The aim of this study was to describe changes in frailty in spine care during the coronavirus disease 2019 (COVID-19) pandemic and their relation to surgical management and outcomes. METHODS: Patients hospitalized for spine pathologies between January 1, 2019, and May 17, 2022, within a nationwide network of 76 hospitals in Germany were retrospectively included. Patient frailty, types of surgery, and in-hospital mortality rates were compared between pandemic and pre-pandemic periods. RESULTS: Of the 223,418 included patients with spine pathologies, 151,766 were admitted during the pandemic and 71,652 during corresponding pre-pandemic periods in 2019. During the pandemic, the proportion of high-frailty patients increased from a range of 5.1-6.1% to 6.5-8.8% (p < 0.01), while the proportion of low frailty patients decreased from a range of 70.5-71.4% to 65.5-70.1% (p < 0.01). In most phases of the pandemic, the Elixhauser comorbidity index (ECI) showed larger increases among high compared to low frailty patients (by 0.2-1.8 vs. 0.2-0.8 [p < 0.01]). Changes in rates of spine surgery were associated with frailty, most clearly in rates of spine fusion, showing consistent increases among low frailty patients (by 2.2-2.5%) versus decreases (by 0.3-0.8%) among high-frailty patients (p < 0.02). Changes in rates of in-hospital mortality were not associated with frailty. CONCLUSIONS: During the COVID-19 pandemic, the proportion of high-frailty patients increased among those hospitalized for spine pathologies in Germany. Low frailty was associated with a rise in rates of spine surgery and high frailty with comparably larger increases in rates of comorbidities.

Trends in frailty in brain tumor care during the COVID-19 pandemic in a nationwide hospital network in Germany.

PURPOSE: Among brain tumor patients, frailty is associated with poor outcomes. The COVID-19 pandemic has led to increased frailty in the general population. To date, evidence on changes in frailty among brain tumor patients during the pandemic is lacking. We aimed to compare frailty among brain tumor patients in Germany during the COVID-19 pandemic to the pre-pandemic era and to assess potential effects on brain tumor care. METHODS: In this retrospective observational study, we compared frailty among brain tumor patients hospitalized during the COVID-19 pandemic in years 2020 through 2022 to pre-pandemic years 2016 through 2019 based on administrative data from a nationwide network of 78 hospitals in Germany. Using the Hospital Frailty Risk Score (HFRS), frailty was categorized as low, intermediate, or high. We examined changes in frailty, patient demographics, the burden of comorbidity, rates of surgery, and mortality rates for different frailty groups during the pandemic and compared them to pre-pandemic levels. RESULTS: Of the 20,005 included hospitalizations for brain tumors, 7979 were during the pandemic (mean age 60.0 years (± 18.4); females: 49.8%), and 12,026 in the pre-pandemic period (mean age: 59.0 years [± 18.4]; females: 49.2%). Average daily admissions decreased from 8.2 (± 5.1) during pre-pandemic years to 7.3 (± 4.5) during the pandemic (p < 0.01). The overall median HFRS decreased from 3.1 (IQR: 0.9-7.3) during the pre-pandemic years to 2.6 (IQR: 0.3-6.8) during the pandemic (p < 0.01). At the same time, the Elixhauser Comorbidity Index (ECI) decreased from 17.0 (± 12.4) to 16.1 (± 12.0; p < 0.01), but to a larger degree among high compared to low frailty cases (by 1.8 vs. 0.3 points; p = 0.04). In the entire cohort, the mean length of stay was significantly shorter in the pandemic period (9.5 days [± 10.7]) compared with pre-pandemic levels (10.2 days [± 11.8]; p < 0.01) with similar differences in the three frailty groups. Rates of brain tumor resection increased from 29.9% in pre-pandemic years to 36.6% during the pandemic (p < 0.001) without differences between frailty levels. Rates of in-hospital mortality did not change during the pandemic (6.1% vs. 6.7%, p = 0.07), and there was no interaction with frailty. CONCLUSION: Even though our findings are limited in that the HFRS is validated only for patients ≥ 75 years of age, our study among patients of all ages hospitalized for brain tumors in Germany suggests a marked decrease in levels of frailty and in the burden of comorbidities during the COVID-19 pandemic.

Neurosurgical care for patients with high-grade gliomas during the coronavirus disease 2019 pandemic: Analysis of routine billing data of a German nationwide hospital network.

Background: Little is known about delivery of neurosurgical care, complication rate and outcome of patients with high-grade glioma (HGG) during the coronavirus disease 2019 (Covid-19) pandemic. Methods: This observational, retrospective cohort study analyzed routine administrative data of all patients admitted for neurosurgical treatment of an HGG within the Helios Hospital network in Germany. Data of the Covid-19 pandemic (March 1, 2020-May 31, 2022) were compared to the pre-pandemic period (January 1, 2016-February 29, 2020). Frequency of treatment and outcome (in-hospital mortality, length of hospital stay [LOHS], time in intensive care unit [TICU] and ventilation outside the operating room [OR]) were separately analyzed for patients with microsurgical resection (MR) or stereotactic biopsy (STBx). Results: A total of 1763 patients underwent MR of an HGG (648 patients during the Covid-19 pandemic; 1115 patients in the pre-pandemic period). 513 patients underwent STBx (182 [pandemic]; 331 patients [pre-pandemic]). No significant differences were found for treatment frequency (MR: 2.95 patients/week [Covid-19 pandemic] vs. 3.04 patients/week [pre-pandemic], IRR 0.98, 95% CI: 0.89-1.07; STBx (1.82 [Covid-19 pandemic] vs. 1.86 [pre-pandemic], IRR 0.96, 95% CI: 0.80-1.16, P > .05). Rates of in-hospital mortality, infection, postoperative hemorrhage, cerebral ischemia and ventilation outside the OR were similar in both periods. Overall LOHS was significantly shorter for patients with MR and STBx during the Covid-19 pandemic. Conclusions: The Covid-19 pandemic did not affect the frequency of neurosurgical treatment of patients with an HGG based on data of a large nationwide hospital network in Germany. LOHS was significantly shorter but quality of neurosurgical care and outcome was not altered during the Covid-19 pandemic.

Decompressive Surgery in the Treatment of Acute Ischemic Stroke during the First Four Waves of the COVID-19 Pandemic in Germany: A Nationwide Observational Cohort Study.

BACKGROUND: The COVID-19 pandemic has significantly affected acute ischemic stroke (AIS) care. In this study, we examined the effects of the pandemic on neurosurgical AIS care by means of decompressive surgery (DS). METHODS: In this retrospective observational study, we compared the characteristics, in-hospital processes, and in-hospital mortality rates among patients hospitalized for AIS during the first four waves of the pandemic (between January 1, 2020 and October 26, 2021) versus the corresponding periods in 2019 (prepandemic). We used administrative data from a nationwide hospital network in Germany. RESULTS: Of the 177 included AIS cases with DS, 60 were from 2019 and 117 from the first four pandemic waves. Compared with the prepandemic levels, there were no changes in weekly admissions for DS during the pandemic. The same was true for patient age (range: 51.7-60.4 years), the number of female patients (range: 33.3-57.1%), and the prevalence of comorbidity, as measured by the Elixhauser Comorbidity Index (range: 13.2-20.0 points). Also, no alterations were observed in transfer to the intensive care unit (range: 87.0-100%), duration of in-hospital stay (range: 14.6-22.7 days), and in-hospital mortality rates (range: 11.8-55.6%). CONCLUSION: In Germany, compared with the prepandemic levels, AIS patients undergoing DS during the first four waves of the pandemic showed no changes in demographics, rates of comorbidity, and in-hospital mortality rates. This is in contrast to previous evidence on patients with less critical types of AIS not requiring DS and underlines the uniqueness of the subgroup of AIS patients requiring DS. Our findings suggests that these patients, in contrast to AIS patients in general, were unable to forgo hospitalization during the COVID-19 pandemic. Maintaining the delivery of DS is an essential aspect of AIS care during a pandemic.

Effects of the COVID-19 Pandemic on Spinal Fusion Procedures for Spinal Infections in a Nationwide Hospital Network in Germany.

BACKGROUND: The full impact of the COVID-19 pandemic on surgical spine care is difficult to assess due to a lack in nationwide evidence from more recent phases of the pandemic. We aimed to describe changes in in-hospital processes associated with spinal fusion procedures in the treatment of spinal infections (SI) during different phases of the pandemic. METHODS: In this retrospective observational study, we examined the in-hospital prevalence and outcomes of spinal fusion procedures for SI (along with patient characteristics, rates of transfer to intensive care units, and mortality rates) during the first four waves of the pandemic compared with the corresponding prepandemic periods in 2019. We used administrative data from a nationwide network of 76 hospitals managing 7% of all in-hospital cases in Germany. RESULTS: We observed no significant change in the prevalence of SI fusion procedures during the pandemic, neither in total numbers (349 vs. 373) nor for each wave separately. On a patient level, we found no differences in age, sex, and the prevalence of paresis, and no relevant differences in associated comorbidities. The rate of mechanical ventilation did not change during any of the examined pandemic waves: it ranged between 9.5 and 18.6% during the pandemic and 3.1 and 16.0% during the corresponding prepandemic control periods. The rate of transfer to intensive care changed only during wave 4 (from 70.4 to 54.8%; p = 0.046) but not in any other pandemic phases. We observed no changes in in-hospital mortality rates (range: 2.9-9.7% vs. 6.2-11.3%) or in duration of hospital stay (range: 26.2-30.8 days vs. 20.8-29.2 days). CONCLUSIONS: The main finding of our study is that within this nationwide network of spine care centers in Germany, the delivery of surgical treatment of SI by means of spinal fusion procedures was maintained throughout the first four waves of the pandemic. Furthermore, there were no relevant changes in patient demographics, in-hospital processes, and mortality rates.

Microscope-Based Augmented Reality with Intraoperative Computed Tomography-Based Navigation for Resection of Skull Base Meningiomas in Consecutive Series of 39 Patients.

BACKGROUND: The aim of surgery for skull base meningiomas is maximal resection with minimal damage to the involved cranial nerves and cerebral vessels; thus, implementation of technologies for improved orientation in the surgical field, such as neuronavigation and augmented reality (AR), is of interest. METHODS: Included in the study were 39 consecutive patients (13 male, 26 female, mean age 64.08 ± 13.5 years) who underwent surgery for skull base meningiomas using microscope-based AR and automatic patient registration using intraoperative computed tomography (iCT). RESULTS: Most common were olfactory meningiomas (6), cavernous sinus (6) and clinoidal (6) meningiomas, meningiomas of the medial (5) and lateral (5) sphenoid wing and meningiomas of the sphenoidal plane (5), followed by suprasellar (4), falcine (1) and middle fossa (1) meningiomas. There were 26 patients (66.6%) who underwent gross total resection (GTR) of the meningioma. Automatic registration applying iCT resulted in high accuracy (target registration error, 0.82 ± 0.37 mm). The effective radiation dose of the registration iCT scans was 0.58 ± 1.05 mSv. AR facilitated orientation in the resection of skull base meningiomas with encasement of cerebral vessels and compression of the optic chiasm, as well as in reoperations, increasing surgeon comfort. No injuries to critical neurovascular structures occurred. Out of 35 patients who lived to follow-up, 33 could ambulate at their last presentation. CONCLUSION: A microscope-based AR facilitates surgical orientation for resection of skull base meningiomas. Registration accuracy is very high using automatic registration with intraoperative imaging.

The Metalloprotease-Disintegrin ADAM8 Alters the Tumor Suppressor miR-181a-5p Expression Profile in Glioblastoma Thereby Contributing to Its Aggressiveness.

Glioblastoma (GBM) as the most common and aggressive brain tumor is characterized by genetic heterogeneity, invasiveness, radio-/chemoresistance, and occurrence of GBM stem-like cells. The metalloprotease-disintegrin ADAM8 is highly expressed in GBM tumor and immune cells and correlates with poor survival. In GBM, ADAM8 affects intracellular kinase signaling and increases expression levels of osteopontin/SPP1 and matrix metalloproteinase 9 (MMP9) by an unknown mechanism. Here we explored whether microRNA (miRNA) expression levels could be regulators of MMP9 expression in GBM cells expressing ADAM8. Initially, we identified several miRNAs as dysregulated in ADAM8-deficient U87 GBM cells. Among these, the tumor suppressor miR-181a-5p was significantly upregulated in ADAM8 knockout clones. By inhibiting kinase signaling, we found that ADAM8 downregulates expression of miR-181a-5p via activation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling suggesting an ADAM8-dependent silencing of miR-181a-5p. In turn, mimic miR-181a-5p transfection caused decreased cell proliferation and lower MMP9 expression in GBM cells. Furthermore, miR-181a-5p was detected in GBM cell-derived extracellular vesicles (EVs) as well as patient serum-derived EVs. We identified miR-181a-5p downregulating MMP9 expression via targeting the MAPK pathway. Analysis of patient tissue samples (n=22) revealed that in GBM, miR-181a-5p is strongly downregulated compared to ADAM8 and MMP9 mRNA expression, even in localized tumor areas. Taken together, we provide evidence for a functional axis involving ADAM8/miR-181a-5p/MAPK/MMP9 in GBM tumor cells.

Radiogenomic Predictors of Recurrence in Glioblastoma-A Systematic Review.

Glioblastoma, as the most aggressive brain tumor, is associated with a poor prognosis and outcome. To optimize prognosis and clinical therapy decisions, there is an urgent need to stratify patients with increased risk for recurrent tumors and low therapeutic success to optimize individual treatment. Radiogenomics establishes a link between radiological and pathological information. This review provides a state-of-the-art picture illustrating the latest developments in the use of radiogenomic markers regarding prognosis and their potential for monitoring recurrence. Databases PubMed, Google Scholar, and Cochrane Library were searched. Inclusion criteria were defined as diagnosis of glioblastoma with histopathological and radiological follow-up. Out of 321 reviewed articles, 43 articles met these inclusion criteria. Included studies were analyzed for the frequency of radiological and molecular tumor markers whereby radiogenomic associations were analyzed. Six main associations were described: radiogenomic prognosis, MGMT status, IDH, EGFR status, molecular subgroups, and tumor location. Prospective studies analyzing prognostic features of glioblastoma together with radiological features are lacking. By reviewing the progress in the development of radiogenomic markers, we provide insights into the potential efficacy of such an approach for clinical routine use eventually enabling early identification of glioblastoma recurrence and therefore supporting a further personalized monitoring and treatment strategy.

Initial Intraoperative Experience with Robotic-Assisted Pedicle Screw Placement with Cirq® Robotic Alignment: An Evaluation of the First 70 Screws.

BACKGROUND: Robot-guided spine surgery is based on a preoperatively planned trajectory that is reproduced in the operating room by the robotic device. This study presents our initial experience with thoracolumbar pedicle screw placement using Brainlab's Cirq® surgeon-controlled robotic arm (BrainLab, Munich, Germany). METHODS: All patients who underwent robotic-assisted implantation of pedicle screws in the thoracolumbar spine were included in the study. Our workflow, consisting of preoperative imagining, screw planning, intraoperative imaging with automatic registration, fusion of the preoperative and intraoperative imaging with a review of the preplanned screw trajectories, robotic-assisted insertion of K-wires, followed by a fluoroscopy-assisted insertion of pedicle screws and control iCT scan, is described. RESULTS: A total of 12 patients (5 male and 7 females, mean age 67.4 years) underwent 13 surgeries using the Cirq® Robotic Alignment Module for thoracolumbar pedicle screw implantation. Spondylodiscitis, metastases, osteoporotic fracture, and spinal canal stenosis were detected. A total of 70 screws were implanted. The mean time per screw was 08:27 ± 06:54 min. The mean time per screw for the first 7 surgeries (first 36 screws) was 16:03 ± 09:32 min and for the latter 6 surgeries (34 screws) the mean time per screw was 04:35 ± 02:11 min (p < 0.05). Mean entry point deviation was 1.9 ± 1.23 mm, mean deviation from the tip of the screw was 2.61 ± 1.6 mm and mean angular deviation was 3.5° ± 2°. For screw-placement accuracy we used the CT-based Gertzbein and Robbins System (GRS). Of the total screws, 65 screws were GRS A screws (92.85%), one screw was a GRS B screw, and two further screws were grade C. Two screws were D screws (2.85%) and underwent intraoperative revision. There were no perioperative deficits. CONCLUSION: Brainlab's Cirq® Robotic Alignment surgeon-controlled robotic arm is a safe and beneficial method for accurate thoracolumbar pedicle screw placement with high accuracy.

Utilizing Intraoperative Navigated 3D Color Doppler Ultrasound in Glioma Surgery.

BACKGROUND: In glioma surgery, the patient's outcome is dramatically influenced by the extent of resection and residual tumor volume. To facilitate safe resection, neuronavigational systems are routinely used. However, due to brain shift, accuracy decreases with the course of the surgery. Intraoperative ultrasound has proved to provide excellent live imaging, which may be integrated into the navigational procedure. Here we describe the visualization of vascular landmarks and their shift during tumor resection using intraoperative navigated 3D color Doppler ultrasound (3D iUS color Doppler). METHODS: Six patients suffering from glial tumors located in the temporal lobe were included in this study. Intraoperative computed tomography was used for registration. Datasets of 3D iUS color Doppler were generated before dural opening and after tumor resection, and the vascular tree was segmented manually. In each dataset, one to four landmarks were identified, compared to the preoperative MRI, and the Euclidean distance was calculated. RESULTS: Pre-resectional mean Euclidean distance of the marked points was 4.1 ± 1.3 mm (mean ± SD), ranging from 2.6 to 6.0 mm. Post-resectional mean Euclidean distance was 4.7. ± 1.0 mm, ranging from 2.9 to 6.0 mm. CONCLUSION: 3D iUS color Doppler allows estimation of brain shift intraoperatively, thus increasing patient safety. Future implementation of the reconstructed vessel tree into the navigational setup might allow navigational updating with further consecutive increasement of accuracy.

Neurosurgical Management and Outcome Parameters in 237 Patients with Spondylodiscitis.

Surgical treatment of spondylodiscitis allows for rapid mobilization and shortens hospital stays, which makes surgical treatment the first-line therapy. We aim to describe our experiences with operative treatment on spondylodiscitis and to determine the parameters that are important in the prediction of outcomes. A retrospective review identified 237 patients who were operatively treated for spondylodiscitis in our institution between January 2010 and December 2018. Clinical data were collected through review of electronic records and relevant imaging. In all cases, contrast-enhancing MRI from the infected region of the spine was obtained. Leukocyte count and C-reactive protein concentrations (CRP) were determined in all the patients. We included 237 patients in the study, 87 female (36.7%) and 150 male (63.3%), with a mean age of 71.4 years. Mean follow-up was 31.6 months. Forty-five patients had spondylodiscitis of the cervical, 73 of the thoracic, and 119 of the lumbosacral spine. All the patients with spondylodiscitis of the cervical spine received instrumentation. In thoracic and lumbar spine decompression, surgery without instrumentation was performed in 26 patients as immediate surgery and in a further 28 patients in the early stages following admission, while 138 patients received instrumentation. Eighty-nine patients (37.6%) had concomitant infections. Infection healing occurred in 89% of patients. Favorable outcomes were noted in patients without concomitant infections, with a normalized CRP value and in patients who received antibiotic therapy for more than six weeks (p < 0.05). Unfavorable outcomes were noted in patients with high CRP, postoperative spondylodiscitis, and recurrent spondylodiscitis (p < 0.05). Application of antibiotic therapy for more than six weeks and normalized CRP showed a correlation with favorable outcomes, whereas concomitant infections showed a correlation with unfavorable outcomes. A detailed screening for concomitant infectious diseases is recommended.

Imaging-based programming of subthalamic nucleus deep brain stimulation in Parkinson's disease.

BACKGROUND: The need for imaging-guided optimization of Deep Brain Stimulation (DBS) parameters is increasing with recent developments of sophisticated lead designs offering highly individualized, but time-consuming and complex programming. OBJECTIVE: The objective of this study was to compare changes in motor symptoms of Parkinson's Disease (PD) and the corresponding volume of the electrostatic field (VEsF) achieved by DBS programming using GUIDE XT™, a commercially available software for visualization of DBS leads within the patient-specific anatomy from fusions of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans, versus standard-of-care clinical programming. METHODS: Clinical evaluation was performed to identify the optimal set of parameters based on clinical effects in 29 patients with PD and bilateral directional leads for Subthalamic Nucleus (STN) DBS. A second DBS program was generated in GUIDE XT™ based on a VEsF optimally located within the dorsolateral STN. Reduction of motor symptoms (Movement Disorders Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS) and the overlap of the corresponding VEsF of both programs were compared. RESULTS: Clinical and imaging-guided programming resulted in a significant reduction in the MDS-UPDRS scores compared to off-state. Motor symptom control with GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. The overlap of the two VEsF did not correlate with the difference in motor symptom reduction by the programs. CONCLUSIONS: Imaging-guided programming of directional DBS leads using GUIDE XT™ is possible without computational background and leads to non-inferior motor symptom control compared with clinical programming. DBS programs based on patient-specific imaging data may thus serve as starting point for clinical testing and may promote more efficient DBS programming.

Intraoperative Computed Tomography-Based Navigation with Augmented Reality for Lateral Approaches to the Spine.

Background. Lateral approaches to the spine have gained increased popularity due to enabling minimally invasive access to the spine, less blood loss, decreased operative time, and less postoperative pain. The objective of the study was to analyze the use of intraoperative computed tomography with navigation and the implementation of augmented reality in facilitating a lateral approach to the spine. Methods. We prospectively analyzed all patients who underwent surgery with a lateral approach to the spine from September 2016 to January 2021 using intraoperative CT applying a 32-slice movable CT scanner, which was used for automatic navigation registration. Sixteen patients, with a median age of 64.3 years, were operated on using a lateral approach to the thoracic and lumbar spine and using intraoperative CT with navigation. Indications included a herniated disc (six patients), tumors (seven), instability following the fracture of the thoracic or lumbar vertebra (two), and spondylodiscitis (one). Results. Automatic registration, applying intraoperative CT, resulted in high accuracy (target registration error: 0.84 ± 0.10 mm). The effective radiation dose of the registration CT scans was 6.16 ± 3.91 mSv. In seven patients, a control iCT scan was performed for resection and implant control, with an ED of 4.51 ± 2.48 mSv. Augmented reality (AR) was used to support surgery in 11 cases, by visualizing the tumor outline, pedicle screws, herniated discs, and surrounding structures. Of the 16 patients, corpectomy was performed in six patients with the implantation of an expandable cage, and one patient underwent discectomy using the XLIF technique. One patient experienced perioperative complications. One patient died in the early postoperative course due to severe cardiorespiratory failure. Ten patients had improved and five had unchanged neurological status at the 3-month follow up. Conclusions. Intraoperative computed tomography with navigation facilitates the application of lateral approaches to the spine for a variety of indications, including fusion procedures, tumor resection, and herniated disc surgery.

Diffusion Kurtosis Imaging Fiber Tractography of Major White Matter Tracts in Neurosurgery.

Diffusion tensor imaging (DTI)-based fiber tractography is routinely used in clinical applications to visualize major white matter tracts, such as the corticospinal tract (CST), optic radiation (OR), and arcuate fascicle (AF). Nevertheless, DTI is limited due to its capability of resolving intra-voxel multi-fiber populations. Sophisticated models often require long acquisition times not applicable in clinical practice. Diffusion kurtosis imaging (DKI), as an extension of DTI, combines sophisticated modeling of the diffusion process with short acquisition times but has rarely been investigated in fiber tractography. In this study, DTI- and DKI-based fiber tractography of the CST, OR, and AF was investigated in healthy volunteers and glioma patients. For the CST, significantly larger tract volumes were seen in DKI-based fiber tractography. Similar results were obtained for the OR, except for the right OR in patients. In the case of the AF, results of both models were comparable with DTI-based fiber tractography showing even significantly larger tract volumes in patients. In the case of the CST and OR, DKI-based fiber tractography contributes to advanced visualization under clinical time constraints, whereas for the AF, other models should be considered.

ADAM8 affects glioblastoma progression by regulating osteopontin-mediated angiogenesis.

Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a median survival of only 15 months. To complement standard treatments including surgery, radiation and chemotherapy, it is essential to understand the contribution of the GBM tumor microenvironment. Brain macrophages and microglia particularly contribute to tumor angiogenesis, a major hallmark of GBM. ADAM8, a metalloprotease-disintegrin strongly expressed in tumor cells and associated immune cells of GBMs, is related to angiogenesis and correlates with poor clinical prognosis. However, the specific contribution of ADAM8 to GBM tumorigenesis remains elusive. Knockdown of ADAM8 in U87 glioma cells led to significantly decreased angiogenesis and tumor volumes of these cells after stereotactic injection into striate body of mice. We found that the angiogenic potential of ADAM8 in GBM cells and in primary macrophages is mediated by the regulation of osteopontin (OPN), an important inducer of tumor angiogenesis. By in vitro cell signaling analyses, we demonstrate that ADAM8 regulates OPN via JAK/STAT3 pathway in U87 cells and in primary macrophages. As ADAM8 is a dispensable protease for physiological homeostasis, we conclude that ADAM8 could be a tractable target to modulate angiogenesis in GBM with minor side-effects.

Extreme lateral interbody fusion (XLIF) in a consecutive series of 72 patients.

Extreme lateral interbody fusion (XLIF) has become the standard of minimally invasive lumbar segmental scoliosis treatment. Our objective is to determine the safety and efficacy of XLIF in spinal canal stenosis (SCS) and spondylodiscitis (SD). Patients treated with XLIF in our department between 2012 and 2018 were retrospectively analyzed. Patient records with clinical and radiographical parameters were evaluated. The patient cohort consists of 40 male and 32 female patients with a median age of 66.6 years. Forty-five patients had an SCS and 27 patients SD. The mean follow-up was 23 months. One level XLIF was performed in 49 patients, 2 levels in 15, 3 levels in 7 patients and 4 levels in 1 patient. All but one patient received an additional dorsal stabilization. The pain was present in all patients with a mean Visual Analogue Scale (VAS) score of 8.8 vs. postoperative VAS of 2.8 (p<0.05). Preoperative neurological deficits were found in 44 patients. Only 6 patients had a neurological deterioration, 45 patients improved, and 21 patients remained unchanged. One patient experienced a perioperative complication.  Non-fusion occurred in 8 cases. There were no outcome differences regarding pain and radiological outcome between patients with SCS and SD as well as between patients with one level vs. multilevel surgery. Baseline characteristics and the radiological outcome did not differ between the two groups. Patients with SD had a higher rate of worsening of neurological deficits following surgery, a higher rate of non-fusion, and a longer hospital stay. Patients with spinal canal stenosis SCS had a longer surgery time and more frequent adjacent segment disease.

Fiber tractography of the optic radiations: impact of diffusion model, voxel shape and orientation.

BACKGROUND: Reliable visualization of the optic radiations (OR) is of major importance in tumor surgery close to the OR to prevent permanent visual field deficits. Diffusion tensor imaging (DTI) based fiber tractography (FT) has become a standard tool to visualize major white matter tracts and to support the prevention of postoperative deficits. Nevertheless, FT of the OR is notoriously challenging due to its high neuroanatomical complexity. METHODS: To improve FT of the OR we analyzed the effect of a more complex diffusion model and the effect of different voxel shapes and orientations. MRI data of 21 healthy subjects was acquired using isometric and anisometric voxel sizes and standard and adapted slice angulation. FT was performed using the DTI based approach and an orientation distribution function (ODF) based approach. Results were visually inspected, and fiber tract volumes were compared. RESULTS: DTI based FT led to poor results, failing to reconstruct plausible tracts at all in up to 26.11% of all cases. The ODF based approach resulted in more compound and solid tracts showing also significantly larger tract volumes. Voxel shape or orientation did not influence DTI, but ODF based FT. Isometric or anisometric voxels with standard slice orientation revealed highest tract volumes. Adapted orientation in combination with anisometric voxels led to significantly smaller tract volumes. CONCLUSIONS: Plausible tractography of the OR can be achieved using ODF based fiber tracking within a clinically feasible timeframe. Voxel shape and orientation seem to be of minor importance and might be kept to isometric voxel for flexible application of FT.

Comparing Fiducial-Based and Intraoperative Computed Tomography-Based Registration for Frameless Stereotactic Brain Biopsy.

OBJECTIVE: The aim of this work was to compare fiducial-based and intraoperative computed tomography (iCT)-based registration for frameless stereotactic brain biopsy. METHODS: Of 50 frameless stereotactic biopsies with the VarioGuide, 30 cases were registered as iCT based and 20 as fiducial based. Statistical analysis of the target registration error (TRE), dose length product, effective radiation dose (ED), operation time, and diagnostic yield was performed. RESULTS: The mean TRE was significantly lower using iCT-based registration (mean ± SD: 0.70 ± 0.32 vs. 2.43 ± 0.73 mm, p < 0.0001). The ED was significantly lower when using iCT-based registration compared to standard navigational CT (mean ± SD: 0.10 ± 0.13 vs. 2.23 ± 0.34 mSv, p < 0.0001). Post-biopsy iCT was associated with a significant lower (p < 0.0001) ED compared to standard CT (mean ± SD: 1.04 ± 0.18 vs. 1.65 ± 0.26 mSv). The mean surgical time was shorter using iCT-based registration, although the mean total operating room (OR) time did not differ significantly. The diagnostic yield was 96.7% (iCT group) versus 95% (fiducial group). Post-biopsy imaging revealed severe bleeding in 3.3% (iCT group) versus 5% (fiducial group). CONCLUSION: iCT-based registration for frameless stereotactic biopsies increases the accuracy significantly without negative effects on the surgical time or the overall time in the OR. Appropriate scan protocols in iCT registration contribute to a significant reduction of the radiation exposure. The high accuracy of the iCT makes it the more favorable registration strategy when taking biopsies of small tumors or lesions near eloquent brain areas.

Application of an Expandable Cage for Reconstruction of the Cervical Spine in a Consecutive Series of Eighty-Six Patients.

Background and objectives: Expandable cages are frequently used to reconstruct the anterior spinal column after a corpectomy. In this retrospective study, we evaluated the perioperative advantages and disadvantages of corpectomy reconstruction with an expandable cage. Materials and Methods: Eighty-six patients (45 male and 41 female patients, medium age of 61.3 years) were treated with an expandable titanium cage for a variety of indications from January 2012 to December 2019 and analyzed retrospectively. The mean follow-up was 30.7 months. Outcome was measured by clinical examination and visual analogue scale (VAS); myelopathy was classified according to the EMS (European Myelopathy Scale) and gait disturbances with the Nurick score. Radiographic analysis comprised measurement of fusion, subsidence and the C2-C7 angle. Results: Indications included spinal canal stenosis with myelopathy (46 or 53.5%), metastasis (24 or 27.9%), spondylodiscitis (12 or 14%), and fracture (4 or 4.6%). In 39 patients (45.3%), additional dorsal stabilization (360° fusion) was performed. In 13 patients, hardware failure occurred, and in 8 patients, adjacent segment disease occurred. Improvement of pain symptoms, myelopathy, and gait following surgery were statistically significant (p < 0.05), with a medium preoperative VAS of 8, a postoperative score of 3.2, and medium EMS scores of 11.3 preoperatively vs. 14.3 postoperatively. Radiographic analysis showed successful fusion in 74 patients (86%). As shown in previous studies, correction of the C2-C7 angle did not correlate with improvement of neurological symptoms. Conclusion: Our results show that expandable titanium cages are a safe and useful tool in anterior cervical corpectomies for providing adequate anterior column support and stability.