The management of patients with spinal metastases (SM) requires a multidisciplinary team of specialists involved in oncological care. Surgical management has evolved significantly over the recent ...years, which warrants reevaluation of its role in the oncological treatment concept. Any patient with a SM was screened for study inclusion. We report baseline characteristics, surgical procedures, complication rates, functional status and outcome of a large consecutive cohort undergoing surgical treatment according to an algorithm. 667 patients underwent 989 surgeries with a mean age of 65 years (min/max 20-94) between 2007 and 2018. The primary cancers mostly originated from the prostate (21.7%), breast (15.9%) and lung (10.0%). Surgical treatment consisted of dorsoventral stabilization in 69.5%, decompression without instrumentation in 12.5% and kyphoplasty in 18.0%. Overall survival reached 18.4 months (95% CI 9.8-26.9) and the median KPS increased by 10 within hospital stay. Surgical management of SMs should generally represent the first step of a conclusive treatment algorithm. The need to preserve long-term symptom control and biomechanical stability requires a surgical strategy currently not supported by level I evidence.
Connectomic comparison of mouse and human cortex Loomba, Sahil; Straehle, Jakob; Gangadharan, Vijayan ...
Science (American Association for the Advancement of Science),
07/2022, Letnik:
377, Številka:
6602
Journal Article
Recenzirano
Odprti dostop
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.
The difference between human and mouse
Over the past few decades, the mouse has become a model organism for brain research. Because of the close evolutionary similarity of ion channels, synaptic receptors, and other key molecular constituents of the brain to that of humans, corresponding similarity has been assumed for cortical neuronal circuits. However, comparative synaptic-resolution connectomic studies are required to determine the degree to which circuit structure has evolved between species. Using three-dimensional electron microscopy, Loomba
et al
. compared mouse and human/macaque cortex synaptic connectivity. Although human cells are much larger compared with mouse neurons and are more numerous, on average, they do not receive more synapses. And, even though there are three times more interneurons in the human cortex than in the mouse, the excitation-to-inhibition ratio is similar between the species. —PRS
Three-dimensional electron microscopy of mouse, macaque, and human brain samples elucidates cell type composition and synaptic circuit architecture.
INTRODUCTION
The analysis of the human brain is a central goal of neuroscience, but for methodological reasons, research has focused on model organisms, the mouse in particular. Because substantial homology was found at the level of ion channels, transcriptional programs, and basic neuronal types, a strong similarity of neuronal circuits across species has also been assumed. However, a rigorous test of the configuration of local neuronal circuitry in mouse versus human—in particular, in the gray matter of the cerebral cortex—is missing.
The about 1000-fold increase in number of neurons is the most obvious evolutionary change of neuronal network properties from mouse to human. Whether the structure of the local cortical circuitry has changed as well is, however, unclear. Recent data from transcriptomic analyses has indicated an increase in the proportion of inhibitory interneurons from mouse to human. But what the effect of such a change is on the circuit configurations found in the human cerebral cortex is not known. This is, however, of particular interest also to the study of neuropsychiatric disorders because in these, the alteration of inhibitory-to-excitatory synaptic balance has been identified as one possible mechanistic underpinning.
RATIONALE
We used recent methodological improvements in connectomics to acquire data from one macaque and two human individuals, using biopsies of the temporal, parietal, and frontal cortex. Human tissue was obtained from neurosurgical interventions related to tumor removal, in which access path tissue was harvested that was not primarily affected by the underlying disease. A key concern in the analysis of human patient tissue has been the relation to epilepsy surgery, when the underlying disease has required often year-long treatment with pharmaceuticals, plausibly altering synaptic connectivity. Therefore, the analysis of nonepileptic surgery tissue seemed of particular importance. We also included data from one macaque individual, who was not known to have any brain-related pathology.
RESULTS
We acquired three-dimensional electron microscopy data from temporal and frontal cortex of human and temporal and parietal cortex of macaque. From these, we obtained connectomic reconstructions and compared these with five connectomes from mouse cortex. On the basis of these data, we were able to determine the effect of the about 2.5-fold expansion of the interneuron pool in macaque and human cortex compared with that of mouse. Contrary to expectation, the inhibitory-to-excitatory synaptic balance on pyramidal neurons in macaque and human cortex was not substantially altered. Rather, the interneuron pool was selectively expanded for bipolar-type interneurons, which prefer the innervation of other interneurons, and which further increased their preference for interneuron innervation from mouse to human. These changes were each multifold, yielding in effect an about 10-fold expanded interneuron-to-interneuron network in the human cortex that is only sparsely present in mouse. The total amount of synaptic input to pyramidal neurons, however, did not change according to the threefold thickening of the cortex; rather, a modest increase from about 12,000 synaptic inputs in mouse to about 15,000 in human was found.
CONCLUSION
The principal cells of the cerebral cortex, pyramidal neurons, maintain almost constant inhibitory-to-excitatory input balance and total synaptic input across 100 million years of evolutionary divergence, which is particularly noteworthy with the concomitant 1000-fold expansion of the neuronal network size and the 2.5-fold increase of inhibitory interneurons from mouse to human. Rather, the key network change from mouse to human is an expansion of almost an order of magnitude of an interneuron-to-interneuron network that is virtually absent in mouse but constitutes a substantial part of the human cortical network. Whether this new network is primarily created through the expansion of existing neuronal types, or is related to the creation of new interneuron subtypes, requires further study. The discovery of this network component in human cortex encourages detailed analysis of its function in health and disease.
Connectomic screening across mammalian species: Comparison of five mouse, two macaque, and two human connectomic datasets from the cerebral cortex.
(
A
) Automated reconstructions of all neurons with their cell bodies in the volume shown, using random colors. The analyzed connectomes comprised a total of ~1.6 million synapses. Arrows indicate evolutionary divergence: the last common ancestor between human and mouse, approximately 100 million years ago, and the last common ancestor between human and macaque, about 20 million years ago. (
B
) Illustration of the about 10-fold expansion of the interneuron-to-interneuron network from mouse to human.
Abstract
Cauda equina syndrome (CES) presents a surgical emergency with treatment required within 48 h. Symptoms include reduced saddle sensation, micturition difficulties, and/or anal sphincter ...impairment. Controversy exists regarding the effect on and coincidence of overweight with CES. We performed a retrospective case–control study of all patients treated surgically for acute complete and incomplete CES in our neurosurgical department from 2009 to 2020, focusing on the preoperative BMI and postoperative neurological outcome. In addition, we performed a comprehensive literature review. Fifty patients with CES were included, of whom 96% suffered from a decompensated lumbar spinal stenosis or disc prolapse between the L4/5 and L5/S1 levels. Our cohort population was overweight but not obese: mean BMI was 27.5 kg/m
2
, compared with 27.6 kg/m
2
in patients with degenerative spine surgery. BMI did not significantly influence the postoperative outcome, but it did affect preoperative symptoms and surgery duration. Symptom duration significantly differed depending on the underlying cause for CES. The literature review revealed sparse evidence, with only four clinical case series presenting contradictory results. We provide a comprehensive literature review on the current evidence regarding CES and obesity and conclude that we did not observe an association between obesity and CES occurrence. Patients with CES and other degenerative spinal pathologies belong to an overweight but not obese population. Body Mass Index has an impact on preoperative symptoms but not clinical outcome in acute CES.
Objectives
To compare spinal bone measures derived from automatic and manual assessment in routine CT with dual energy X-ray absorptiometry (DXA) in their association with prevalent osteoporotic ...vertebral fractures using our fully automated framework (
https://anduin.bonescreen.de
) to assess various bone measures in clinical CT.
Methods
We included 192 patients (141 women, 51 men; age 70.2 ± 9.7 years) who had lumbar DXA and CT available (within 1 year). Automatic assessment of spinal bone measures in CT included segmentation of vertebrae using a convolutional neural network (CNN), reduction to the vertebral body, and extraction of bone mineral content (BMC), trabecular and integral volumetric bone mineral density (vBMD), and CT-based areal BMD (aBMD) using asynchronous calibration. Moreover, trabecular bone was manually sampled (manual vBMD).
Results
A total of 148 patients (77%) had vertebral fractures and significantly lower values in all bone measures compared to patients without fractures (
p
≤ 0.001). Except for BMC, all CT-based measures performed significantly better as predictors for vertebral fractures compared to DXA (e.g., AUC = 0.885 for trabecular vBMD and AUC = 0.86 for integral vBMD vs. AUC = 0.668 for DXA aBMD, respectively; both
p
< 0.001). Age- and sex-adjusted associations with fracture status were strongest for manual vBMD (OR = 7.3, 95% CI 3.8–14.3) followed by automatically assessed trabecular vBMD (OR = 6.9, CI 3.5–13.4) and integral vBMD (OR = 4.3, CI 2.5–7.6). Diagnostic cutoffs of integral vBMD for osteoporosis (< 160 mg/cm
3
) or low bone mass (160 ≤ BMD < 190 mg/cm
3
) had sensitivity (84%/41%) and specificity (78%/95%) similar to trabecular vBMD.
Conclusions
Fully automatic osteoporosis screening in routine CT of the spine is feasible. CT-based measures can better identify individuals with reduced bone mass who suffered from vertebral fractures than DXA.
Key Points
•
Opportunistic osteoporosis screening of spinal bone measures derived from clinical routine CT is feasible in a fully automatic fashion using a deep learning-driven framework (
https://anduin.bonescreen.de
).
•
Manually sampled volumetric BMD (vBMD) and automatically assessed trabecular and integral vBMD were the best predictors for prevalent vertebral fractures.
•
Except for bone mineral content, all CT-based bone measures performed significantly better than DXA-based measures.
•
We introduce diagnostic thresholds of integral vBMD for osteoporosis (< 160 mg/cm
3
) and low bone mass (160 ≤ BMD < 190 mg/cm
3
) with almost equal sensitivity and specificity compared to conventional thresholds of quantitative CT as proposed by the American College of Radiology (osteoporosis < 80 mg/cm
3
).
Abstract Background Cement augmented pedicle screw instrumentation (CAPSI) of the thoracolumbar spine is indicated in osteoporosis or osteopenia to improve pullout strength and biomechanical ...stability of pedicle screws (PS). Only few studies report on the incidence of pulmonary cement embolism or other complications associated with CAPSI. Purpose Aim of this retrospective study was to assess the rate of CAPSI associated complications. Study Design Retrospective cohort study. Patient Sample Patients who underwent CAPSI due to spinal tumors or degenerative spine disease. Outcome Measures Cement leakage, pulmonary cement embolism (PCE), mortality rate. Methods Our clinical database was reviewed for patients who underwent CAPSI between January 2012 and June 2015. A total of 165 patients (mean age 71 ± 11.2; range: 46-93 years; m=62, f=103) were included. Indications were osteoporotic fractures (n=40), spinal metastases (n=57), degenerative (n=49), infectious spine disease (n=5) or traumatic fractures (n=14) with an associated osteoporosis. Every patient received between 2 and 21 (mean 8 ± 3.3) cement augmented PS in the thoracolumbar and lumbosacral spine. Both, intraoperative cement leakage in prevertebral veins, the inferior vena cava and/or pulmonary arteries and leakage detected on postoperative imaging were evaluated. We assessed the incidence of clinically symptomatic and asymptomatic events. Results In 29 of 31 patients with intraoperative suspicion of cement leakage into prevertebral veins or the inferior vena cava on lateral fluoroscopy, which were without hemodynamic relevance, cement extrusion was confirmed on postoperative X-ray or CT scan. In three of eight patients with suspicion of pulmonary cement embolism (PCE), PCE was verified on thoracic CT. Four patients experienced life-threatening intraoperative hemodynamic reactions, either due to cement embolism (n=2; 1.2%) or anaphylactic shock (n=2; 1.2%) with need of intraoperative CPR in three cases. Two patients deceased due to fulminant PCE. Three patients with dyspnea one day after surgery were also confirmed with PCE on chest CT. In five patients an asymptomatic PCE was found incidentally on postoperative imaging. In additional 68 patients cement leakage into prevertebral veins or the ascending cava vein was found incidentally on postoperative spine X-ray or CT. Two out of 10 patients with intraspinal epidural cement leakage required revision surgery. 110 patients of the 165 patients (66.7%) had clinically asymptomatic cement leakage. 13 patients had PCE (7.9%) of whom 5 (3.0%) were symptomatic. Two patients experienced intraoperative cement induced anaphylaxia (1.2%). The overall symptomatic complication rate was 5.5 % (n=9). The 30-day mortality rate was 1.8% (n=3). Conclusion CAPSI bears a high risk of asymptomatic cement leakage. The risk for associated severe complications was also relatively high and probably underestimated considering the retrospective nature of this study. A strict indication for cement augmentation, especially in patients with cardiac predisposition should be the consequence. We doubt that technical aspects of cement application and/or different types of cement are capable to reduce the risk of these complications substantially.
Objective
Aneurysm residuals after clipping are a well-known problem, but the course of aneurysm remnants in follow-up is not well studied. No standards or follow-up guidelines exist for treatment of ...aneurysm remnants. The aim of this study was to evaluate the risk factors for postoperative aneurysm remnants and their changes during follow-up.
Methods
We performed a retrospective analysis of 666 aneurysms treated via clipping in our hospital from 2006 to 2016. Postoperative and follow-up angiographic data were analyzed for aneurysm remnants and regrowth. Clinical parameters and aneurysm-specific characteristics were correlated with radiological results.
Results
The frequency of aneurysm residuals was 12% (78/666). Aneurysms located in the middle cerebral artery (
p
= 0.02) showed a significantly lower risk for incomplete aneurysm occlusion. Larger aneurysms with a diameter of 11–25 mm (
p
= 0.005) showed a significantly higher risk for incomplete aneurysm occlusion. Five patients underwent re-clipping during the same hospital stay. Remnants were stratified based on morphological characteristics into “dog ears” (
n
= 60) and “broad based” (
n
= 13). The majority of the “dog ears” stayed stable, decreased in size, or vanished during follow-up. Broad-based remnants showed a higher risk of regrowth.
Conclusions
A middle cerebral artery location seems to lower the risk for the incomplete clip occlusion of an aneurysm. Greater aneurysm size (11–25 mm) is associated with a postoperative aneurysm remnant. The majority of “dog-ear” remnants appear to remain stable during follow-up. In these cases, unnecessarily frequent angiographic checks could be avoided. By contrast, broad-based residuals show a higher risk of regrowth that requires close imaging controls if retreatment cannot be performed immediately.
Objectives
To investigate the value of contrast-enhanced (CE) turbo spin echo black blood (BB) sequences for imaging of therapy-naive high-grade gliomas (HGGs).
Methods
Consecutive patients with ...histopathologically confirmed World Health Organization (WHO) grade III or IV gliomas and no oncological treatment prior to index imaging (March 2019 to January 2020) were retrospectively included. Magnetic resonance imaging (MRI) at 3 Tesla comprised CE BB and CE turbo field echo (TFE) sequences. The lack/presence of tumor-related contrast enhancement and satellite lesions were evaluated by two readers. Sharper delineation of tumor boundaries (1, bad; 2, intermediate; 3, good delineation) and vaster expansion of HGGs into the adjacent brain parenchyma on CE BB imaging were the endpoints. Furthermore, contrast-to-noise ratios (CNRs) were calculated and compared between sequences.
Results
Fifty-four patients were included (mean age: 61.2 ± 15.9 years, 64% male). The vast majority of HGGs (51/54) showed contrast enhancement in both sequences, while two HGGs as well as one of six detected satellite lesions were depicted in CE BB imaging only. Tumor boundaries were significantly sharper (R1: 2.43 ± 0.71 vs. 2.73 ± 0.62,
p
< 0.001; R2: 2.44 ± 0.74 vs. 2.77 ± 0.60,
p
= 0.001), while the spread of HGGs into the adjacent parenchyma was larger when considering CE BB sequences according to both readers (larger spread in CE BB sequences: R1: 23 patients; R2: 20 patients). The CNR for CE BB sequences significantly exceeded that of CE TFE sequences (43.4 ± 27.1 vs. 32.5 ± 25.0,
p
= 0.0028).
Conclusions
Our findings suggest that BB imaging may considerably improve delineation of therapy-naive HGGs when compared with established TFE imaging. Thus, CE BB sequences might supplement MRI protocols for brain tumors.
Key Points
• This study investigated contrast-enhanced (CE) T1-weighted black blood (BB) sequences for improved MRI in patients with therapy-naive high-grade gliomas (HGGs).
• Compared with conventionally used turbo field echo (TFE) sequences, CE BB sequences depicted tumor boundaries and spread of HGGs into adjacent parenchyma considerably better, which also showed higher CNRs.
• Two enhancing tumor masses and one satellite lesion were exclusively identified in CE BB sequences, but remained undetected in conventionally used CE TFE sequences.
Navigated transcranial magnetic stimulation (nTMS) is a newly evolving technique. Despite its supposed purpose (for example, preoperative central region mapping), little is known about its accuracy ...compared with established modalities like direct cortical stimulation (DCS) and functional MR (fMR) imaging. Against this background, the authors performed the current study to compare the accuracy of nTMS with DCS and fMR imaging.
Fourteen patients with tumors in or close to the precentral gyrus were examined using nTMS for motor cortex mapping, as were 12 patients with lesions in the subcortical white matter motor tract. Moreover, preoperative fMR imaging and intraoperative mapping of the motor cortex were performed via DCS, and the outlining of the motor cortex was compared.
In the 14 cases of lesions affecting the precentral gyrus, the primary motor cortex as outlined by nTMS correlated well with that delineated by intraoperative DCS mapping, with a deviation of 4.4 ± 3.4 mm between the two methods. In comparing nTMS with fMR imaging, the deviation between the two methods was much larger: 9.8 ± 8.5 mm for the upper extremity and 14.7 ± 12.4 mm for the lower extremity. In 13 of 14 cases, the surgeon admitted easier identification of the central region because of nTMS. The procedure had a subjectively positive influence on the operative results in 5 cases and was responsible for a changed resection strategy in 2 cases. One of 26 patients experienced nTMS as unpleasant; none found it painful.
Navigated TMS correlates well with DCS as a gold standard despite factors that are supposed to contribute to the inaccuracy of nTMS. Moreover, surgeons have found nTMS to be an additional and helpful modality during the resection of tumors affecting eloquent motor areas, as well as during preoperative planning.
Abstract
Complications in spine surgery can arise in the intraoperative or the immediate postoperative period or in a delayed manner. These complications may lead to severe or even permanent ...morbidity if left undiagnosed and untreated. We prospectively interviewed 526 patients out of 1140 patients who consecutively underwent spinal surgery in our department between November 2017 and November 2018 and analysed the outcome and complication rates. A 12 months follow-up period was also adopted. We analysed the patients’ clinical characteristics, comorbidities, surgical management, survival rates, and outcomes. Risk factor analyses for the development of complications were also performed. Patients’ median age was 67 years (range: 13–96). The main diagnoses were as follows: degenerative in 50%, tumour in 22%, traumatic fractures in 13%, infections in 10%, reoperations in 3%, and others in 2%. Surgeries were emergency procedures (within 24 h) in 12%. Furthermore, 59% required instrumentation. The overall postoperative complication rate was 26%. Revision surgery was required in 12% of cases within 30 postoperative days (median time to revision 11 days IQR 5–15 days). The most frequent complications included wound healing disorders, re-bleeding, and CSF leakage. Thereby, the risk factor analysis revealed age-adjusted CCI (p = 0.01), metastatic tumour (p = 0.01), and atrial fibrillation (p = 0.02) as significant risk factors for postoperative complications. Additionally, postoperative KPS (p = 0.004), postoperative anaemia (p = 0.001), the length of hospital stay (p = 0.02), and duration of surgery (p = 00.002) were also identified as associated factors. Complication rates after spinal surgeries are still high, especially in patients with metastatic tumour disease and poor clinical status (KPS), requiring revision surgeries in several cases. Therefore, specific risk factors should be determined to carefully select surgery groups.
Introduction
Glioblastoma multiforme (GBM) is a highly malignant glial tumor, affecting men more often than women. The reason for this gender-specific predominance remains unclear, raising the ...question whether these effects are subject to hormonal control. The purpose of this study was to examine the expression of estrogen receptor alpha (ERα) and aromatase in human GBM tissue samples in relation to patient survival and furthermore to investigate the effect of standard chemotherapy in combination with estradiol treatment on glioblastoma tumor cell lines in vitro.
Methods
60 tissue samples (31 male, 29 female) of GBM patients were analysed with immunohistochemistry for ERα and aromatase for survival analyses. The cell lines LN18 and LN229 were treated with 17β-estradiol (E2) in different dosing regimens and the cell viability was measured with MTT assay. After estradiol pre-treatment Temozolomide was added and tested again.
Results
High expression of ERα and aromatase in the GBM tissue samples was associated with significantly longer survival times of GBM patients, regardless of gender and body-mass-index. The treatment with high concentrations of estradiol resulted in lower tumor cell viability, compared to control. The cells significantly showed a stronger sensitivity against Temozolomid (TMZ) after estradiol pre-treatment.
Conclusion
ERα-expression of glial tumour cells seems to play an important prognostic role as a biomarker in GBM, as well as the expression of the enzyme Aromatase. The combined treatment of GBM with standard chemotherapy and estradiol may be beneficial to patient’s survival.
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