Resolving spatial response heterogeneity in glioblastoma.

PURPOSE: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity. METHODS: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated. RESULTS: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance. CONCLUSION: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future.

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors.

BACKGROUND: The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by neuropathology. METHODS: In this phase II noninferiority, prospective, multicenter, nonrandomized, off-label clinical trial (EudraCT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a noninferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS. RESULTS: A total of 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high-grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%). A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with 0.87 versus 0.91 for FS, resulting in a difference of 0.04 (95% confidence interval -0.10; 0.02; P = .367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; P < .001). CONCLUSIONS: CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real time with a 10-fold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.

CTA Supplemented by CTP Increases Interrater Reliability and Endovascular Treatment Use in Patients with Aneurysmal SAH.

BACKGROUND AND PURPOSE: Cerebral vasospasm is a common complication of aneurysmal SAH and remains a risk factor for delayed cerebral ischemia and poor outcome. The interrater reliability of CTA in combination with CTP has not been sufficiently studied. We aimed to investigate the reliability of CTA alone and in combination with CTP in the detection of cerebral vasospasm and the decision to initiate endovascular treatment. MATERIALS AND METHODS: This is a retrospective single-center study including patients treated for aneurysmal SAH. Inclusion criteria were a baseline CTA and follow-up imaging including CTP due to suspected vasospasm. Three neuroradiologists were asked to grade 15 intracranial arterial segments in 71 cases using a tripartite scale (no, mild <50%, or severe >50% vasospasm). Raters further evaluated whether endovascular treatment should be indicated. The ratings were performed in 2 stages with a minimum interval of 6 weeks. The first rating included only CTA images, whereas the second rating additionally encompassed CTP images. All raters were blinded to any clinical information of the patients. RESULTS: Interrater reliability for per-segment analysis of vessels was highly variable (κ = 0.16-0.61). We observed a tendency toward higher interrater reliability in proximal vessel segments, except for the ICA. CTP did not improve the reliability for the per-segment analysis. When focusing on senior raters, the addition of CTP images resulted in higher interrater reliability for severe vasospasm (κ = 0.28; 95% CI, 0.10-0.46 versus κ = 0.46; 95% CI, 0.26-0.66) and subsequently higher concordance (κ = 0.23; 95% CI, -0.01-0.46 versus κ = 0.73; 95% CI, 0.55-0.91) for the decision of whether endovascular treatment was indicated. CONCLUSIONS: CTA alone offers only low interrater reliability in the graduation of cerebral vasospasm. However, using CTA in combination with CTP might help, especially senior neuroradiologists, to increase the interrater reliability to identify severe vasospasm following aneurysmal SAH and to increase the reliability regarding endovascular treatment decisions.

Early and recurrent cerebral vasospasms after aneurysmal subarachnoid hemorrhage: The impact of age.

INTRODUCTION: Cerebral vasospasms remain a strong predictor of poor outcome after aneurysmal SAH. The aim of this study was to describe the time course of relevant vasospasms after aneurysmal SAH and to determine the variables associated with early-onset or prolonged and recurrent vasospasms. PATIENTS AND METHODS: We conducted a retrospective, single-center study of consecutive adult patients with aneurysmal SAH admitted between 2016 and 2022 at our tertiary stroke center. Relevant vasospasms, defined as vessel narrowing detected in DSA in combination with clinical deterioration or new perfusion deficit, were detected according to our in-house algorithm and eventually treated endovascularly. The primary endpoint was the diagnosis of relevant vasospasms. As secondary endpoints, the time from hemorrhage to the onset of vasospasms and the time from the first to the last endovascular intervention were measured. RESULTS: Of 368 patients with aneurysmal SAH, 135 (41.0%) developed relevant vasospasms. The median time between ictus and detection of vasospasms was 8 days (IQR: 6-10). Patients with early-onset vasospasms were significantly younger (mean 52.7 ± 11.2 years vs 58.7 ± 11.5 years, p = 0.003) and presented more frequently vasospasm-related infarctions at discharge (58.8% vs 38.7%, p = 0.03). In 74 patients (54.8%), recurrent relevant vasospasms were observed despite endovascular treatment. Younger age and early onset were significantly associated with longer duration of relevant vasospasms (both p < 0.05). DISCUSSION AND CONCLUSION: Younger age was associated with early-onset and longer duration of relevant vasospasms in this study. More frequent clinical and diagnostic follow-up should be considered in this subgroup of patients that are at risk for poor outcomes.

Clinical, radiological and pathological features of temporomesial tumors in the adult. A single center experience from 15 years.

Introduction: The mesial temporal lobe plays a distinct role in epileptogenesis, and tumors in this part of the brain potentially have specific clinical and radiological features. Differentiating high-grade from lower-grade tumors or non-neoplastic lesions can be challenging, preventing the decision for early resection that can be critical in high-grade tumors. Methods: A brain tumor database was analyzed retrospectively to identify patients with temporomesial tumors. We determined clinical features (age, sex, symptoms leading to clinical presentation) as well as neuroradiological (tumor location and the presence of contrast enhancement on initial magnetic resonance imaging (MRI)) and neuropathological findings. Results: We identified 324 temporal tumors. 39 involved the mesial temporal lobe. 77% of temporomesial tumors occured in males, and 77% presented with seizures, regardless of tumor type or grade. In patients 50 years or older, 90% were male and 80% had glioblastoma (GBM); there was no GBM in patients younger than 50 years. 50% of GBMs lacked contrast enhancement. Male sex was significantly associated with GBM. In both contrast-enhancing and non-enhancing tumors, age of 50 years or older was also significantly associated with GBM. Conclusion: In middle-aged and older patients with a mesial temporal lobe tumor, GBM is the most likely diagnosis even when there is no MRI contrast enhancement. Prolonged diagnostic workup or surveillance strategies should be avoided and early resection may be justified in these patients.

sEMG-based prediction of human forearm movements utilizing a biomechanical model based on individual anatomical/ physiological measures and a reduced set of optimization parameters.

For assistive devices such as active orthoses, exoskeletons or other close-to-body robotic-systems, the immediate prediction of biological limb movements based on biosignals in the respective control system can be used to enable intuitive operation also by untrained users e.g. in healthcare, rehabilitation or industrial scenarios. Surface electromyography (sEMG) signals from the muscles that drive the limbs can be measured before the actual movement occurs and, hence, can be used as source for predicting limb movements. The aim of this work was to create a model that can be adapted to a new user or movement scenario with little measurement and computing effort. Therefore, a biomechanical model is presented that predicts limb movements of the human forearm based on easy to measure sEMG signals of the main muscles involved in forearm actuation (lateral and long head of triceps and short and long head of biceps). The model has 42 internal parameters of which 37 were attributed to 8 individually measured physiological measures (location of acromion at the shoulder, medial/lateral epicondyles as well as olecranon at the elbow, and styloid processes of radius/ulna at the wrist; maximum muscle forces of biceps and triceps). The remaining 5 parameters are adapted to specific movement conditions in an optimization process. The model was tested in an experimental study with 31 subjects in which the prediction quality of the model was assessed. The quality of the movement prediction was evaluated by using the normalized mean absolute error (nMAE) for two arm postures (lower, upper), two load conditions (2 kg, 4 kg) and two movement velocities (slow, fast). For the resulting 8 experimental combinations the nMAE varied between nMAE = 0.16 and nMAE = 0.21 (lower numbers better). An additional quality score (QS) was introduced that allows direct comparison between different movements. This score ranged from QS = 0.25 to QS = 0.40 (higher numbers better) for the experimental combinations. The above formulated aim was achieved with good prediction quality by using only 8 individual measurements (easy to collect body dimensions) and the subsequent optimization of only 5 parameters. At the same time, just easily accessible sEMG measurement locations are used to enable simple integration, e.g. in exoskeletons. This biomechanical model does not compete with models that measure all sEMG signals of the muscle heads involved in order to achieve the highest possible prediction quality.

Postoperative Communicating Hydrocephalus Following Grade 2/3 Glioma Resection: Incidence, Timing and Risk Factors.

BACKGROUND: In diffusely infiltrating gliomas, the maximum extent of tumor resection is an important predictor of overall survival, irrespective of histological or molecular subtype or tumor grade. For glioblastoma WHO grade 4 (GBM), it has been shown that resection-related events, such as ventricular opening and ventriculitis, increase the risk for development of communicating hydrocephalus (CH) requiring cerebrospinal fluid (CSF) diversion surgery. Risk factors for the development and the incidence of hydrocephalus following resection of other types of infiltrating gliomas are less well established. In this study, we evaluated the incidence and timing of occurrence of different types of hydrocephalus and potential risk factors for the development of CH following resection of grade 2 and 3 gliomas. METHODS: 346 patients who underwent tumor resection (WHO grade 2: 42.2%; 3: 57.8%) at our department between 2006 and 2019 were analyzed retrospectively. For each patient, age, sex, WHO grade, histological type, IDH mutation and 1p/19q codeletion status, tumor localization, number of resections, rebleeding, ventriculitis, ventricular opening during resection and postoperative CSF leak were determined. Uni- as well as multivariate analyses were performed to identify associations with CH and independent risk factors. RESULTS: 24 out of 346 (6.9%) patients needed CSF diversion surgery (implantation of a ventriculoperitoneal or ventriculoatrial shunt) following resection. Nineteen patients (5.5%) had CH, on median, 44 days after the last resection (interquartile range: 18-89 days). Two patients had obstructive hydrocephalus (OH), and three patients had other CSF circulation disorders. CH was more frequent in grade 3 compared to grade 2 gliomas (8.5 vs. 1.4%). WHO grade 3 (odds ratio (OR) 7.5, p = 0.00468), rebleeding (OR 5.0, p = 0.00984), ventriculitis (OR 4.1, p = 0.00463) and infratentorial tumor localization (OR 6.6, p = 0.00300) were identified as significant independent risk factors for the development of post-resection CH. Ventricular opening was significantly associated with CH, but it was not an independent risk factor. CONCLUSION: Physicians treating brain tumor patients should be aware that postoperative CH requiring CSF shunting occurs not only in GBM but also after resection of lower-grade gliomas, especially in grade 3 tumors. It usually occurs several weeks after resection. Rebleeding and postoperative ventriculitis are independent risk factors.

Imaging the WHO 2021 Brain Tumor Classification: Fully Automated Analysis of Imaging Features of Newly Diagnosed Gliomas.

BACKGROUND: The fifth version of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) in 2021 brought substantial changes. Driven by the enhanced implementation of molecular characterization, some diagnoses were adapted while others were newly introduced. How these changes are reflected in imaging features remains scarcely investigated. MATERIALS AND METHODS: We retrospectively analyzed 226 treatment-naive primary brain tumor patients from our institution who received extensive molecular characterization by epigenome-wide methylation microarray and were diagnosed according to the 2021 WHO brain tumor classification. From multimodal preoperative 3T MRI scans, we extracted imaging metrics via a fully automated, AI-based image segmentation and processing pipeline. Subsequently, we examined differences in imaging features between the three main glioma entities (glioblastoma, astrocytoma, and oligodendroglioma) and particularly investigated new entities such as astrocytoma, WHO grade 4. RESULTS: Our results confirm prior studies that found significantly higher median CBV (p = 0.00003, ANOVA) and lower median ADC in contrast-enhancing areas of glioblastomas, compared to astrocytomas and oligodendrogliomas (p = 0.41333, ANOVA). Interestingly, molecularly defined glioblastoma, which usually does not contain contrast-enhancing areas, also shows significantly higher CBV values in the non-enhancing tumor than common glioblastoma and astrocytoma grade 4 (p = 0.01309, ANOVA). CONCLUSIONS: This work provides extensive insights into the imaging features of gliomas in light of the new 2021 WHO CNS tumor classification. Advanced imaging shows promise in visualizing tumor biology and improving the diagnosis of brain tumor patients.

Brain metastases in the elderly - Impact of residual tumor volume on overall survival.

Background: Due to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival. Objectives: The aim of this study was to analyze the impact of resection and residual tumor volume on clinical outcome and overall survival (OS) in elderly patients suffering from BM. Methods: Patients ≥ 75 years who had surgery for BM between April 2007 and January 2020 were retrospectively included. Residual tumor burden (RTB) was determined by segmentation of early postoperative brain MRI (72 h). Contrast-enhancing tumor subvolumes were segmented manually. "Postoperative tumor volume" refers to the targeted BMs. Impact of preoperative Karnofsky performance status scale (KPSS), age, sex and RTB on OS was analyzed. Survival analyses were performed using Kaplan-Meier estimates for the univariate analysis and the Cox regression proportional hazards model for the multivariate analysis. Results: One hundred and one patients were included. Median age at surgery was 78 years (IQR 76-81). Sixty-two patients (61%) had a single BM; 16 patients (16%) had two BMs; 13 patients (13%) had three BMs; and 10 patients (10%) had more than three BMs. Median preoperative tumor burden was 10.3 cm3 (IQR 5-25 cm3), and postoperative tumor burden was 0 cm3 (IQR 0-1.1 cm3). Complete cytoreduction (RTB = 0) was achieved in 52 patients (52%). Complete resection of the targeted metastases was achieved in 78 patients (78%). Median OS was 7 months (IQR 2-11). In univariate analysis, high preoperative KPSS (HR 0.986, 95% CI 0.973-0.998, p = 0.026) and small postoperative tumor burden (HR 1.025, 95% CI 1.002-1.047, p = 0.029) were significantly associated with prolonged OS. Patients with RTB = 0 survived significantly longer than those with residual tumor did (12 [IQR 5-19] vs. 5 [IQR 3-7] months, p = 0.007). Furthermore, prolongation of survival was significantly associated with surgery in patients with favorable KPSS, with an adjusted HR of 0.986 (p = 0.026). However, there were no significances regarding age. Conclusions: RTB is a strong predictor for prolonged OS, regardless of age or cancer type. Postoperative MRI should confirm the extent of resection, as intraoperative estimates do not warrant a complete resection. It is crucial to aim for maximal cytoreduction to achieve the best long-term outcomes for these patients, despite the fact the patients are advanced in age.

Revised historical Northern Hemisphere black carbon emissions based on inverse modeling of ice core records.

Black carbon emitted by incomplete combustion of fossil fuels and biomass has a net warming effect in the atmosphere and reduces the albedo when deposited on ice and snow; accurate knowledge of past emissions is essential to quantify and model associated global climate forcing. Although bottom-up inventories provide historical Black Carbon emission estimates that are widely used in Earth System Models, they are poorly constrained by observations prior to the late 20th century. Here we use an objective inversion technique based on detailed atmospheric transport and deposition modeling to reconstruct 1850 to 2000 emissions from thirteen Northern Hemisphere ice-core records. We find substantial discrepancies between reconstructed Black Carbon emissions and existing bottom-up inventories which do not fully capture the complex spatial-temporal emission patterns. Our findings imply changes to existing historical Black Carbon radiative forcing estimates are necessary, with potential implications for observation-constrained climate sensitivity.

Assessment of the incidence and nature of adverse events and their association with human error in neurosurgery. A prospective observation.

Introduction: Adverse events in surgery are a relevant cause of costs, disability, or death, and their incidence is a key quality indicator that plays an important role in the future of health care. In neurosurgery, little is known about the frequency of adverse events and the contribution of human error. Research question: To determine the incidence, nature and severity of adverse events in neurosurgery, and to investigate the contribution of human error. Material and methods: Prospective observation of all adverse events occurring at an academic neurosurgery referral center focusing on neuro-oncology, cerebrovascular and spinal surgery. All 4176 inpatients treated between September 2019 and September 2020 were included. Adverse events were recorded daily and their nature, severity and a potential contribution of human error were evaluated weekly by all senior neurosurgeons of the department. Results: 25.0% of patients had at least one adverse event. In 25.9% of these cases, the major adverse event was associated with human error, mostly with execution (18.3%) or planning (5.6%) deficiencies. 48.8% of cases with adverse events were severe (≥SAVES-v2 grade 3). Patients with multiple adverse events (8.6%) had more severe adverse events (67.6%). Adverse events were more severe in cranial than in spinal neurosurgery (57.6 vs. 39.4%). Discussion and conclusion: Adverse events occur frequently in neurosurgery. These data can serve as benchmarks when discussing quality-based accreditation and reimbursement in upcoming health care reforms.The high frequency of human performance deficiencies contributing to adverse events shows that there is potential to further eliminate avoidable patient harm.

Manual and semi-automatic determination of elbow angle-independent parameters for a model of the biceps brachii distal tendon based on ultrasonic imaging.

Tendons consist of passive soft tissue with non linear material properties. They play a key role in force transmission from muscle to skeletal structure. The properties of tendons have been extensively examined in vitro. In this work, a non linear model of the distal biceps brachii tendon was parameterized based on measurements of myotendinous junction displacements in vivo at different load forces and elbow angles. The myotendinous junction displacement was extracted from ultrasound B-mode images within an experimental setup which also allowed for the retrieval of the exerted load forces as well as the elbow joint angles. To quantify the myotendinous junction movement based on visual features from ultrasound images, a manual and an automatic method were developed. The performance of both methods was compared. By means of exemplary data from three subjects, reliable fits of the tendon model were achieved. Further, different aspects of the non linear tendon model generated in this way could be reconciled with individual experiments from literature.

Postoperative communicating hydrocephalus following glioblastoma resection: Incidence, timing and risk factors.

Introduction: Glioblastoma (GBM) is the most common malignant primary brain tumor. Treatment includes maximally safe surgical resection followed by radiation and/or chemotherapy. However, resection can lead to ventricular opening, potentially increasing the risk for development of communicating hydrocephalus (CH). Complications such as rebleeding and infection may also lead to CH and, eventually, the need for cerebrospinal fluid (CSF) diversion surgery. In this study, we evaluated the incidence of different types of hydrocephalus and potential risk factors for the development of CH following glioblastoma resection. Methods: 726 GBM patients who underwent tumor resection at our department between 2006 and 2019 were analyzed retrospectively. Potential risk factors that were determined for each patient were age, sex, tumor location, the number of resection surgeries, ventricular opening during resection, postoperative CSF leak, ventriculitis, and rebleeding. Uni- as well as multivariate analyses were performed to identify associations with CH and independent risk factors. Results: 55 patients (7.6%) needed CSF diversion surgery (implantation of a ventriculoperitoneal or ventriculoatrial shunt) following resection surgery. 47 patients (6.5%) had CH, on median, 24 days after the last resection (interquartile range: 17-52 days). 3 patients had obstructive hydrocephalus (OH) and 5 patients had other CSF circulation disorders. Ventricular opening (odds ratio (OR): 7.9; p=0.000807), ventriculitis (OR 3.3; p=0.000754), and CSF leak (OR 2.3; p=0.028938) were identified as significant independent risk factors for the development of post-resection CH. Having more than one resection surgery was associated with CH as well (OR 2.1; p=0.0128), and frontal tumors were more likely to develop CH (OR 2.4; p=0.00275), while temporal tumors were less likely (OR 0.41; p=0.0158); However, none of those were independent risk factors. Age, sex, or rebleeding were not associated with postoperative CH. Conclusion: Postoperative CH requiring CSF shunting is not infrequent following GBM resection and is influenced by surgery-related factors. It typically occurs several weeks after resection. If multiple risk factors are present, one should discuss the possibility of postoperative CH with the patient and maybe even consider pre-emptive shunt implantation to avoid interruption of adjuvant tumor therapy. The incidence of CH requiring shunting in GBM patients could rise in the future.

The Relation of Patient Expectations, Satisfaction, and Outcome in Surgery of the Cervical Spine: A Prospective Study.

STUDY DESIGN: We performed a prospective nonblinded single center observational study. OBJECTIVE: To investigate the relationship between expectations, outcome, and satisfaction with the outcome in patients undergoing cervical spine stabilization surgery. SUMMARY OF BACKGROUND DATA: In modern healthcare, patient-reported outcome measures and patient satisfaction have become an important aspect of quality control. Therefore, outcome benchmarks for specific diseases are highly desired. Numerous studies have investigated patient-reported outcome measures and what constitutes satisfaction in degenerative lumbar spine disease. In cervical spine surgery, it is less clear what drives the postoperative symptom burden and patient satisfaction and how this depends on the primary diagnosis and other patient factors. METHODS: This was a prospective, single center, observational study on patients undergoing cervical spine stabilization surgery for degenerative disease, trauma, infection, or tumor. Using the visual analogue scale for neck and arm pain, the neck disability index (NDI), the modified Japanese Orthopedic Association Score (mJOA) and patient-reported satisfaction, patient status and expectations before surgery, at discharge, 6 and 12 months after surgery were evaluated. RESULTS: One hundred five patients were included. Score-based outcome correlated well with satisfaction at 6 and 12 months. Except for low NDI expectations (≥15 points) that correlated with dissatisfaction, expectations in no other score were correlated with satisfaction. Expectations did influence the outcome in some subgroups and meeting expectations resulted in higher rates of satisfaction. Pain reduction plays an important role for satisfaction, independently from the predominant symptom or pathology. CONCLUSION: Satisfaction correlates well with outcome. Meeting expectations did influence satisfaction with the outcome. The NDI seems to be a valuable preoperative screening tool for poor satisfaction at 12 months. In degenerative pathology, pain is the predominant variable influencing satisfaction independently from the predominant symptom (including myelopathy). LEVEL OF EVIDENCE: 5.

Connectomic comparison of mouse and human cortex.

The human cerebral cortex houses 1000 times more neurons than that of the cerebral cortex of a mouse, but the possible differences in synaptic circuits between these species are still poorly understood. We used three-dimensional electron microscopy of mouse, macaque, and human cortical samples to study their cell type composition and synaptic circuit architecture. The 2.5-fold increase in interneurons in humans compared with mice was compensated by a change in axonal connection probabilities and therefore did not yield a commensurate increase in inhibitory-versus-excitatory synaptic input balance on human pyramidal cells. Rather, increased inhibition created an expanded interneuron-to-interneuron network, driven by an expansion of interneuron-targeting interneuron types and an increase in their synaptic selectivity for interneuron innervation. These constitute key neuronal network alterations in the human cortex.

Surgery in Acute Metastatic Spinal Cord Compression: Timing and Functional Outcome.

Background: Patients with metastatic spinal cord compression (MSCC) may experience long-term functional impairment. It has been established that surgical decompression improves neurological outcomes, but the effect of early surgery remains uncertain. Our objective was to evaluate the impact of early versus late surgery for acute MSCC due to spinal metastases (SM). Methods: We retrospectively reviewed a consecutive cohort of all patients undergoing surgery for SMs at our institution. We determined the prevalence of acute MSCC; the time between acute neurological deterioration as well as between admission and surgery (standard procedure: decompression and instrumentation); and neurological impairment graded by the ASIA scale upon presentation and discharge. Results: We screened 693 patients with surgery for spinal metastasis; 140 patients (21.7%) had acute MSCC, defined as neurological impairment corresponding to ASIA grade D or lower, acquired within 72 h before admission. Non-MSCC patients had surgery for SM-related cauda equina syndrome, radiculopathy and/or spinal instability. Most common locations of the SM in acute MSCC were the thoracic (77.9%) and cervical (10.7%) spine. Per standard of care, acute MSCC patients underwent surgery including decompression and instrumentation, and the median time from admission to surgery was 16 h (interquartile range 10-22 h). Within the group of patients with acute MSCC, those who underwent early surgery (i.e., before the median 16 h) had a significantly higher rate of ASIA improvement by at least one grade at discharge (26.5%) compared to those who had late surgery after 16 h (10.1%; p = 0.024). Except for a significantly higher sepsis rate in the late surgery group, complication rates did not differ between the late and early surgery subgroups. Conclusions: We report data on the largest cohort of patients with MSCC to date. Early surgery is pivotal in acute MSCC, substantially increasing the chance for neurological improvement without increasing complication rates. We found no significant impact when surgery was performed later than 24 h after admission. These findings will provide the framework for a much-needed prospective study. Until then, the treatment strategy should entail the earliest possible surgical intervention.

Low-Energy X-Ray Intraoperative Radiation Therapy (Lex-IORT) for Resected Brain Metastases: A Single-Institution Experience.

BACKGROUND: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. METHOD: Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16-30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan-Meyer analysis were applied. RESULTS: The mean follow-up time was 10.8 months (range, 0-39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3-100%), 71.4% (95%-CI 50.2-92.6%) and 58.0% (95%-CI 34.1-81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required. CONCLUSION: In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis.

Sequential and Hybrid PET/MRI Acquisition in Follow-Up Examination of Glioblastoma Show Similar Diagnostic Performance.

Both positron emission tomography (PET) and magnetic resonance imaging (MRI), including dynamic susceptibility contrast perfusion (DSC-PWI), are crucial for treatment monitoring of patients with high-grade gliomas. In clinical practice, they are usually conducted at separate time points. Whether this affects their diagnostic performance is presently unclear. To this end, we retrospectively reviewed 38 patients with pathologically confirmed glioblastoma (IDH wild-type) and suspected tumor recurrence after radiotherapy. Only patients who received both a PET−MRI (where DSC perfusion was acquired simultaneously with a FET-PET) and a separate MRI exam (including DSC perfusion) were included. Tumors were automatically segmented into contrast-enhancing tumor (CET), necrosis, and edema. To compare the simultaneous as well as the sequential DSC perfusion to the FET-PET, we calculated Dice overlap, global mutual information as well as voxel-wise Spearman correlation of hotspot areas. For the joint assessment of PET and MRI, we computed logistic regression models for the differentiation between true progression (PD) and treatment-related changes (TRC) using simultaneously or sequentially acquired images as input data. We observed no significant differences between Dice overlap (p = 0.17; paired t-test), mutual information (p = 0.18; paired t-test) and Spearman correlation (p = 0.90; paired t-test) when comparing simultaneous PET−MRI and sequential PET/MRI acquisition. This also held true for the subgroup of patients with >14 days between exams. Importantly, for the diagnostic performance, ROC analysis showed similar AUCs for differentiation of PD and TRC (AUC simultaneous PET: 0.77; AUC sequential PET: 0.78; p = 0.83, DeLong's test). We found no relevant differences between simultaneous and sequential acquisition of FET-PET and DSC perfusion, also regarding their diagnostic performance. Given the increasing attention to multi-parametric assessment of glioma treatment response, our results reassuringly suggest that sequential acquisition is clinically and scientifically acceptable.

Motion parallax for object localization in electric fields.

Parallax, as a visual effect, is used for depth perception of objects. But is there also the effect of parallax in the context of electric field imagery? In this work, the example of weakly electric fish is used to investigate how the self-generated electric field that these fish utilize for orientation and communication alike, may be used as a template to define electric parallax. The skin of the electric fish possesses a vast amount of electroreceptors that detect the self-emitted dipole-like electric field. In this work, the weakly electric fish is abstracted as an electric dipole with a sensor line in between the two emitters. With an analytical description of the object distortion for a uniform electric field, the distortion in a dipole-like field is simplified and simulated. On the basis of this simulation, the parallax effect could be demonstrated in electric field images i.e. by closer inspection of voltage profiles on the sensor line. Therefore, electric parallax can be defined as the relative movement of a signal feature of the voltage profile (here, the maximum or peak of the voltage profile) that travels along the sensor line peak trace (PT). The PT width correlates with the object's vertical distance to the sensor line, as close objects create a large PT and distant objects a small PT, comparable with the effect of visual motion parallax.