Brain malignancies can either originate from within the CNS (gliomas) or invade from other locations in the body (metastases). A highly immunosuppressive tumor microenvironment (TME) influences brain ...tumor outgrowth. Whether the TME is predominantly shaped by the CNS micromilieu or by the malignancy itself is unknown, as is the diversity, origin, and function of CNS tumor-associated macrophages (TAMs). Here, we have mapped the leukocyte landscape of brain tumors using high-dimensional single-cell profiling (CyTOF). The heterogeneous composition of tissue-resident and invading immune cells within the TME alone permitted a clear distinction between gliomas and brain metastases (BrM). The glioma TME presented predominantly with tissue-resident, reactive microglia, whereas tissue-invading leukocytes accumulated in BrM. Tissue-invading TAMs showed a distinctive signature trajectory, revealing tumor-driven instruction along with contrasting lymphocyte activation and exhaustion. Defining the specific immunological signature of brain tumors can facilitate the rational design of targeted immunotherapy strategies.
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•Leukocyte invasion is higher in brain metastasis than in CNS-endogenous cancers•The tumor type shapes the differentiation of monocyte-derived macrophages•Brain metastases harbor a high frequency of regulatory T cells•Both activation and exhaustion are prevalent in lymphocytes of the metastatic TME
High-parametric single-cell mapping of the tumor microenvironment of patients with primary brain tumors or brain metastases reveals that the immune response to cancer in the brain is shaped by cancer type, with metastases favoring T cell and monocyte-derived macrophage invasion and gliomas characterized by activated microglia.
During surgeries that put the visual pathway at risk of injury, continuous monitoring of the visual function is desirable. However, the intraoperative monitoring of the visual evoked potential (VEP) ...is not yet widely used. We evaluate here the clinical utility of intraoperative VEP monitoring.
We analyzed retrospectively 46 consecutive surgeries in 2011-2013. High luminance stimulating devices delivered flash stimuli on the closed eyelid during intravenous anesthesia. We monitored VEP features N75 and P100 and took patients' preoperative and postoperative visual function from patient charts. Postoperative ophthalmologic workup was performed in 25 (54%) patients and preoperatively in 28 (61%) patients.
VEP recordings were feasible in 62 of 85 eyes (73%) in 46 patients. All 23 eyes without VEP had impaired vision. During surgery, VEPs remained stable throughout surgery in 50 eyes. In 44 of these, visual function did not deteriorate and three patients (6 eyes) developed hemianopia. VEP decreased transiently in 10 eyes and visual function of all was preserved. VEPs were lost permanently in 2 eyes in two patients without new postoperative visual impairment.
Satisfactory intraoperative VEP monitoring was feasible in all patients except in those with severe visual impairment. Preservation of VEPs predicted preserved visual function. During resection of lesions in the visual cortex, VEP monitoring could not detect new major visual field defects due to injury in the posterior visual pathway. Intraoperative VEPs were sensitive enough to detect vascular damage during aneurysm clipping and mechanical manipulation of the anterior visual pathway in an early reversible stage. Intraoperative VEP monitoring influenced surgical decisions in selected patients and proved to be a useful supplement to the toolbox of intraoperative neurophysiological monitoring.
To improve the transparency of the local health care system, treatment cost was recently referenced to disease related groups. Treatment quality must be legally documented in a patient registry, in ...particular for the highly specialized treatments provided by neurosurgery departments.
In 2013 we have installed a patient registry focused on cranial neurosurgery. Surgeries are characterized by indication, treatment, location and other specific neurosurgical parameters. Preoperative state and postoperative outcome are recorded prospectively using neurological and sociological scales. Complications are graded by their severity in a therapy-oriented complication score system (Clavien-Dindo-Grading system, CDG). Results are presented at the monthly clinical staff meeting.
Data acquisition compatible with the clinic workflow permitted to include all eligible patients into the registry. Until December 2015, we have registered 2880 patients that were treated in 3959 surgeries and 8528 consultations. Since the registry is fully operational (August 2014), we have registered 325 complications on 1341 patient discharge forms (24%). In 64% of these complications, no or only pharmacological treatment was required. At discharge, there was a clear correlation of the severity of the complication and the Karnofsky Performance Status (KPS, ρ = -0.3, slope -6 KPS percentage points per increment of CDG) and the length of stay (ρ = 0.4, slope 1.5 days per increment of CDG).
While the therapy-oriented complication scores correlate reasonably well with outcome and length of stay, they do not account for new deficits that cannot be treated. Outcome grading and complication severity grading thus serve a complimentary purpose. Overall, the registry serves to streamline and to complete information flow in the clinic, to identify complication rates and trends early for the internal quality monitoring and communication with patients. Conversely, the registry influences clinical practice in that it demands rigorous documentation and standard operating procedures.
Background
Visualization, analysis and characterization of the angioarchitecture of a brain arteriovenous malformation (bAVM) present crucial steps for understanding and management of these complex ...lesions. Three-dimensional (3D) segmentation and 3D visualization of bAVMs play hereby a significant role. We performed a systematic review regarding currently available 3D segmentation and visualization techniques for bAVMs.
Methods
PubMed, Embase and Google Scholar were searched to identify studies reporting 3D segmentation techniques applied to bAVM characterization. Category of input scan, segmentation (automatic, semiautomatic, manual), time needed for segmentation and 3D visualization techniques were noted.
Results
Thirty-three studies were included. Thirteen (39%) used MRI as baseline imaging modality, 9 used DSA (27%), and 7 used CT (21%). Segmentation through automatic algorithms was used in 20 (61%), semiautomatic segmentation in 6 (18%), and manual segmentation in 7 (21%) studies. Median automatic segmentation time was 10 min (IQR 33), semiautomatic 25 min (IQR 73). Manual segmentation time was reported in only one study, with the mean of 5–10 min. Thirty-two (97%) studies used screens to visualize the 3D segmentations outcomes and 1 (3%) study utilized a heads-up display (HUD). Integration with mixed reality was used in 4 studies (12%).
Conclusions
A golden standard for 3D visualization of bAVMs does not exist. This review describes a tendency over time to base segmentation on algorithms trained with machine learning. Unsupervised fuzzy-based algorithms thereby stand out as potential preferred strategy. Continued efforts will be necessary to improve algorithms, integrate complete hemodynamic assessment and find innovative tools for tridimensional visualization.
Abstract
Intraoperatively acquired diffusion-weighted imaging (DWI) sequences in cranial tumor surgery are used for early detection of ischemic brain injuries, which could result in impaired ...neurological outcome and their presence might thus influence the neurosurgeon’s decision on further resection. The phenomenon of false-negative DWI findings in intraoperative magnetic resonance imaging (ioMRI) has only been reported in single cases and therefore yet needs to be further analyzed. This retrospective single-center study’s objective was the identification and characterization of false-negative DWI findings in ioMRI with new or enlarged ischemic areas on postoperative MRI (poMRI). Out of 225 cranial tumor surgeries with intraoperative DWI sequences, 16 cases with no additional resection after ioMRI and available in-time poMRI (< 14 days) were identified. Of these, a total of 12 cases showed false-negative DWI in ioMRI (75%). The most frequent tumor types were oligodendrogliomas and glioblastomas (4 each). In 5/12 cases (41.7%), an ischemic area was already present in ioMRI, however, volumetrically increased in poMRI (mean infarct growth + 2.1 cm
3
; 0.48–3.6), whereas 7 cases (58.3%) harbored totally new infarcts on poMRI (mean infarct volume 0.77 cm
3
; 0.05–1.93). With this study we provide the most comprehensive series of false-negative DWI findings in ioMRI that were not followed by additional resection. Our study underlines the limitations of intraoperative DWI sequences for the detection and size-estimation of hyperacute infarction. The awareness of this phenomenon is crucial for any neurosurgeon utilizing ioMRI.
A nuclear protein of testis (NUT) carcinoma, also known as NUT midline carcinoma, is a rare subtype of squamous carcinoma known for its aggressive growth behaviour. It can form anywhere in the body. ...Although, it usually occurs along midline structures (head, neck, lungs). The authors present the first report of intrasellar NUT carcinoma with cavernous sinus infiltration in a 47-year-old patient. MRI showed an inhomogeneous, gadolinium-enhancing lesion with intra- and suprasellar growth, invasion of the cavernous sinus without clear differentiation from normal pituitary tissue. Given the lymphoma diagnosis in the frozen section and invasion of the cavernous sinus, the patient underwent endoscopic, transnasal, and transsphenoidal subtotal resection only. Local tumour and spinal metastases showed a good response to radio-chemotherapy. Despite combined radio-chemotherapy, the patient died of pulmonary insufficiency due to rapid progression of pulmonary metastasis 6 months after the initial diagnosis.
During development and in various diseases of the CNS, new blood vessel formation starts with endothelial tip cell selection and vascular sprout migration, followed by the establishment of ...functional, perfused blood vessels. Here we describe a method that allows the assessment of these distinct angiogenic steps together with antibody-based protein detection in the postnatal mouse brain. Intravascular and perivascular markers such as Evans blue (EB), isolectin B4 (IB4) or laminin (LN) are used alongside simultaneous immunofluorescence on the same sections. By using confocal laser-scanning microscopy and stereological methods for analysis, detailed quantification of the 3D postnatal brain vasculature for perfused and nonperfused vessels (e.g., vascular volume fraction, vessel length and number, number of branch points and perfusion status of the newly formed vessels) and characterization of sprouting activity (e.g., endothelial tip cell density, filopodia number) can be obtained. The entire protocol, from mouse perfusion to vessel analysis, takes ∼10 d.
Background
Residual tumor tissue after pituitary adenoma surgery, is linked with additional morbidity and mortality. Intraoperative magnetic resonance imaging (ioMRI) could improve resection. We aim ...to assess the improvement in gross total resection (GTR), extent of resection (EOR), and residual tumor volume (RV) achieved using ioMRI.
Methods
A systematic review was carried out on PubMed/MEDLINE to identify any studies reporting intra- and postoperative (1) GTR, (2) EOR, or (3) RV in patients who underwent resection of pituitary adenomas with ioMRI. Random effects meta-analysis of the rate of improvement after ioMRI for these three surgical outcomes was intended.
Results
Among 34 included studies (2130 patients), the proportion of patients with conversion to GTR (∆GTR) after ioMRI was 0.19 (95% CI 0.15–0.23). Mean ∆EOR was + 9.07% after ioMRI. Mean ∆RV was 0.784 cm
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. For endoscopically treated patients, ∆GTR was 0.17 (95% CI 0.09–0.25), while microscopic ∆GTR was 0.19 (95% CI 0.15–0.23). Low-field ioMRI studies demonstrated a ∆GTR of 0.19 (95% CI 0.11–0.28), while high-field and ultra-high-field ioMRI demonstrated a ∆GTR of 0.19 (95% CI 0.15–0.24) and 0.20 (95% CI 0.13–0.28), respectively.
Conclusions
Our meta-analysis demonstrates that around one fifth of patients undergoing pituitary adenoma resection convert from non-GTR to GTR after the use of ioMRI. EOR and RV can also be improved to a certain extent using ioMRI. Endoscopic versus microscopic technique or field strength does not appear to alter the impact of ioMRI. Statistical heterogeneity was high, indicating that the improvement in surgical results due to ioMRI varies considerably by center.
Background
Recent technological advances have led to the development and implementation of machine learning (ML) in various disciplines, including neurosurgery. Our goal was to conduct a ...comprehensive survey of neurosurgeons to assess the acceptance of and attitudes toward ML in neurosurgical practice and to identify factors associated with its use.
Methods
The online survey consisted of nine or ten mandatory questions and was distributed in February and March 2019 through the European Association of Neurosurgical Societies (EANS) and the Congress of Neurosurgeons (CNS).
Results
Out of 7280 neurosurgeons who received the survey, we received 362 responses, with a response rate of 5%, mainly in Europe and North America. In total, 103 neurosurgeons (28.5%) reported using ML in their clinical practice, and 31.1% in research. Adoption rates of ML were relatively evenly distributed, with 25.6% for North America, 30.9% for Europe, 33.3% for Latin America and the Middle East, 44.4% for Asia and Pacific and 100% for Africa with only two responses. No predictors of clinical ML use were identified, although academic settings and subspecialties neuro-oncology, functional, trauma and epilepsy predicted use of ML in research. The most common applications were for predicting outcomes and complications, as well as interpretation of imaging.
Conclusions
This report provides a global overview of the neurosurgical applications of ML. A relevant proportion of the surveyed neurosurgeons reported clinical experience with ML algorithms. Future studies should aim to clarify the role and potential benefits of ML in neurosurgery and to reconcile these potential advantages with bioethical considerations.
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