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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.
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In the vibrissal area of rodent somatosensory cortex, information on whisker stimulation is processed by neuronal networks in a corresponding cortical column. To understand how sensory stimuli are represented in a column, it is essential to identify cell types constituting these networks. Layer 6 (L6) comprises 25% of all neurons in a column. In rats, 430 of these are inhibitory interneurons (INs). Little is known about the axon projection of L6 INs with reference to columnar and laminar organization. We quantified axonal projections of L6 INs (n = 68) with reference to columns and layers in somatosensory cortex of rats. We found distinct projection types differentially targeting layers of a cortical column. The majority of L6 INs did not show a column-specific innervation, densely projecting to neighboring columns as well as the home column. However, a small fraction targeted granular and supragranular layers, where axon projections were confined to the home column. We also quantified putative innervation of pyramidal cells as a functional correlate of axonal distribution. Electrophysiological properties were not correlated to axon projection. The quantitative data on axonal projections and electrophysiological properties of L6 INs can guide future studies investigating cortical processing of sensory information at the single cell level.
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Neuronas GABAérgicas/fisiología , Inhibición Neural/fisiología , Vías Nerviosas/fisiología , Corteza Somatosensorial/citología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/efectos de la radiación , Animales , Animales Recién Nacidos , Dendritas , Femenino , Neuronas GABAérgicas/citología , Glutamato Descarboxilasa/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Parvalbúminas/metabolismo , Técnicas de Placa-Clamp , Ratas , Ratas Wistar , VibrisasRESUMEN
A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.
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Algoritmos , Corteza Cerebral/citología , Interneuronas/clasificación , Interneuronas/citología , Terminología como Asunto , Ácido gamma-Aminobutírico/metabolismo , Animales , Teorema de Bayes , Corteza Cerebral/metabolismo , Análisis por Conglomerados , Humanos , Interneuronas/metabolismoRESUMEN
The cellular organization of the cortex is of fundamental importance for elucidating the structural principles that underlie its functions. It has been suggested that reconstructing the structure and synaptic wiring of the elementary functional building block of mammalian cortices, the cortical column, might suffice to reverse engineer and simulate the functions of entire cortices. In the vibrissal area of rodent somatosensory cortex, whisker-related "barrel" columns have been referred to as potential cytoarchitectonic equivalents of functional cortical columns. Here, we investigated the structural stereotypy of cortical barrel columns by measuring the 3D neuronal composition of the entire vibrissal area in rat somatosensory cortex and thalamus. We found that the number of neurons per cortical barrel column and thalamic "barreloid" varied substantially within individual animals, increasing by â¼2.5-fold from dorsal to ventral whiskers. As a result, the ratio between whisker-specific thalamic and cortical neurons was remarkably constant. Thus, we hypothesize that the cellular architecture of sensory cortices reflects the degree of similarity in sensory input and not columnar and/or cortical uniformity principles.
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Modelos Neurológicos , Corteza Somatosensorial/citología , Vibrisas/inervación , Vías Aferentes/citología , Animales , Recuento de Células , Procesamiento de Imagen Asistido por Computador , Microscopía Confocal , Ratas , Ratas WistarRESUMEN
Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in cortical columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a column contains ~2,200 INs (11.5% of ~19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The "hot zones" of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.
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Mapeo Encefálico/métodos , Interneuronas/fisiología , Inhibición Neural/fisiología , Corteza Somatosensorial/citología , Animales , Fluorescencia , Glutamato Descarboxilasa , Inmunohistoquímica , Microscopía Confocal , Ratas , Ratas Wistar , Corteza Somatosensorial/fisiologíaRESUMEN
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.
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Accidente Cerebrovascular , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Adulto , Humanos , Hemorragia Subaracnoidea/complicaciones , Estudios Retrospectivos , Vasoespasmo Intracraneal/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , HospitalizaciónRESUMEN
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.
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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.
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Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Humanos , Angiografía Cerebral/métodos , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/cirugía , Estudios Retrospectivos , Vasoespasmo Intracraneal/diagnóstico por imagen , Vasoespasmo Intracraneal/etiología , Reproducibilidad de los ResultadosRESUMEN
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.
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Neoplasias Encefálicas , Fluoresceína , Secciones por Congelación , Microscopía Confocal , Humanos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/diagnóstico por imagen , Masculino , Microscopía Confocal/métodos , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Secciones por Congelación/métodos , Anciano , Adulto , Estudios de Seguimiento , Adulto Joven , Pronóstico , Anciano de 80 o más AñosRESUMEN
Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type-specific lemniscal synaptic wiring diagram and elucidates structure-function relationships of this physiologically relevant pathway at single-cell resolution.
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Células Receptoras Sensoriales/citología , Células Receptoras Sensoriales/fisiología , Corteza Somatosensorial/citología , Corteza Somatosensorial/fisiología , Tálamo/citología , Tálamo/fisiología , Vibrisas/fisiología , Animales , Red Nerviosa/citología , Red Nerviosa/fisiología , Ratas , Ratas Wistar , Células Receptoras Sensoriales/clasificación , Tacto/fisiología , Vibrisas/citología , Vibrisas/inervaciónRESUMEN
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.
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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.
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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.
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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.
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How does the brain compute? Answering this question necessitates neuronal connectomes, annotated graphs of all synaptic connections within defined brain areas. Further, understanding the energetics of the brain's computations requires vascular graphs. The assembly of a connectome requires sensitive hardware tools to measure neuronal and neurovascular features in all three dimensions, as well as software and machine learning for data analysis and visualization. We present the state of the art on the reconstruction of circuits and vasculature that link brain anatomy and function. Analysis at the scale of tens of nanometers yields connections between identified neurons, while analysis at the micrometer scale yields probabilistic rules of connection between neurons and exact vascular connectivity.
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Automatización/métodos , Encéfalo/citología , Encéfalo/fisiología , Modelos Neurológicos , Vías Nerviosas/fisiología , Neuronas/fisiología , Animales , Humanos , Neuroimagen , Neuronas/clasificación , Dinámicas no Lineales , Retina/citología , Retina/fisiología , Sinapsis/fisiología , Sinapsis/ultraestructuraRESUMEN
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.
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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 12âmonths. 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 12âmonths. In degenerative pathology, pain is the predominant variable influencing satisfaction independently from the predominant symptom (including myelopathy). LEVEL OF EVIDENCE: 5.
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Satisfacción del Paciente , Satisfacción Personal , Vértebras Cervicales/cirugía , Humanos , Motivación , Dolor , Estudios Prospectivos , Resultado del TratamientoRESUMEN
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.
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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.
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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.