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BACKGROUND: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool. METHODS: The RANO resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model was prognostically verified in a separate external validation cohort. RESULTS: Our training cohort compromised 1003 patients with newly diagnosed isocitrate dehydrogenase-wildtype glioblastoma. Residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, age, and postoperative KPS were prognostic for survival and incorporated into regression tree analysis. By individually weighting the prognostic factors, an additive score (range, 0-9 points) integrating these four variables distinguished patients with low (0-2 points), intermediate (3-5 points), and high risk (6-9 points) for inferior survival. The prognostic value of our risk model was retained in treatment-based subgroups and confirmed in an external validation cohort of 258 patients with glioblastoma. Compared to previously postulated models, goodness-of-fit measurements were superior for our model. CONCLUSIONS: The novel RANO risk model serves as an easy-to-use, yet highly prognostic tool for postoperative patient stratification prior to further therapy. The model may serve to guide patient management and reduce imbalances between study arms in prospective trials.
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BACKGROUND: The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined. OBJECTIVE: We hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC. DESIGN: We conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy. RESULTS: Bioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.
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Spatially resolved transcriptomics has revolutionized RNA studies by aligning RNA abundance with tissue structure, enabling direct comparisons between histology and gene expression. Traditional approaches to identifying signature genes often involve preliminary data grouping, which can overlook subtle expression patterns in complex tissues. We present Spatial Gradient Screening, an algorithm which facilitates the supervised detection of histology-associated gene expression patterns without prior data grouping. Utilizing spatial transcriptomic data along with single-cell deconvolution from injured mouse cortex, and TCR-seq data from brain tumors, we compare our methodology to standard differential gene expression analysis. Our findings illustrate both the advantages and limitations of cluster-free detection of gene expression, offering more profound insights into the spatial architecture of transcriptomes. The algorithm is embedded in SPATA2, an open-source framework written in R, which provides a comprehensive set of tools for investigating gene expression within tissue.
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Algoritmos , Perfilação da Expressão Gênica , Transcriptoma , Animais , Camundongos , Perfilação da Expressão Gênica/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Humanos , Análise de Célula Única/métodosRESUMO
The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119+P2RY12+CD68+Iba1+HLA-DR+CD11c+SCAMP2+ microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8+ parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.
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Encéfalo , COVID-19 , Imunidade Inata , Humanos , COVID-19/imunologia , Imunidade Inata/imunologia , Encéfalo/imunologia , Encéfalo/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Microglia/imunologia , Microglia/patologia , Adulto , Linfócitos T CD8-Positivos/imunologia , SARS-CoV-2/imunologia , Cicatriz/imunologia , Cicatriz/patologia , Aprendizado de MáquinaRESUMO
BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement. METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement. RESULTS: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables. CONCLUSIONS: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Glioblastoma/patologia , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Prognóstico , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: In glioblastoma (GBM), the effects of altered glycocalyx are largely unexplored. The terminal moiety of cell coating glycans, sialic acid, is of paramount importance for cell-cell contacts. However, sialic acid turnover in gliomas and its impact on tumor networks remain unknown. METHODS: We streamlined an experimental setup using organotypic human brain slice cultures as a framework for exploring brain glycobiology, including metabolic labeling of sialic acid moieties and quantification of glycocalyx changes. By live, 2-photon and high-resolution microscopy we have examined morphological and functional effects of altered sialic acid metabolism in GBM. By calcium imaging we investigated the effects of the altered glycocalyx on a functional level of GBM networks. RESULTS: The visualization and quantitative analysis of newly synthesized sialic acids revealed a high rate of de novo sialylation in GBM cells. Sialyltrasferases and sialidases were highly expressed in GBM, indicating that significant turnover of sialic acids is involved in GBM pathology. Inhibition of either sialic acid biosynthesis or desialylation affected the pattern of tumor growth and lead to the alterations in the connectivity of glioblastoma cells network. CONCLUSIONS: Our results indicate that sialic acid is essential for the establishment of GBM tumor and its cellular network. They highlight the importance of sialic acid for glioblastoma pathology and suggest that dynamics of sialylation have the potential to be targeted therapeutically.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patologia , Ácido N-Acetilneuramínico/metabolismo , Ácidos Siálicos/metabolismo , Transdução de Sinais , Linhagem Celular TumoralRESUMO
BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. RESULTS: We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, "maximal resection" (class 2) had superior survival compared to "submaximal resection" (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, "supramaximal resection" of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologiaRESUMO
BACKGROUND AND PURPOSE: The diagnostic work-up in patients with spontaneous intracranial hypotension (SIH) and spinal longitudinal extradural CSF collection (SLEC) on magnetic resonance imaging (MRI) comprises dynamic digital subtraction myelography (dDSM) in prone position for leak detection. Dynamic computed tomography (CT) myelography (dCT-M) in prone position follows if the leak is not unequivocally located. A drawback of dCTM is a high radiation dose. This study evaluates the diagnostic needs of dCT-M examinations and measures to reduce radiation doses. METHODS: Frequency, leak sites, length and number of spiral acquisitions, DLP and effective doses of dCTM were retrospectively recorded in patients with ventral dural tears. RESULTS: Of 42 patients with ventral dural tears, 8 underwent 11 dCTM when the leak was not unequivocally shown on digital subtraction myelography. The median number of spiral acquisitions was 4 (range 3-7) and the mean effective radiation dose 30.6 mSv (range 13.1-62.16 mSv) mSv. Five of eight leaks were located in the upper thoracic spine (range C7/Th1-Th2/3). Bolus tracking of intrathecal contrast agent in dCTM was used to limit the number and length of spiral acquisitions. DISCUSSION: A dCTM in prone position to localize a ventral dural tear is needed in every fifth patient with a SLEC on MRI. It is typically needed when the leak is located in the upper thoracic spine and when patients have broad shoulders. Measures to reduce the radiation dose include bolus tracking or to repeat the DSM with adjusted positioning of patient.
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Hipotensão Intracraniana , Humanos , Hipotensão Intracraniana/diagnóstico por imagem , Mielografia/métodos , Vazamento de Líquido Cefalorraquidiano , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos , Doses de RadiaçãoRESUMO
Health-related quality of life (HRQoL) assessment is becoming increasingly important in neurosurgery following the trend toward patient-centered care, especially in the context of skull base diseases. The current study evaluates the systematic assessment of HRQoL using digital patient-reported outcome measures (PROMs) in a tertiary care center specialized in skull base diseases. The methodology and feasibility to conduct digital PROMs using both generic and disease-specific questionnaires were investigated. Infrastructural and patient-specific factors affecting participation and response rates were analyzed. Since August 2020, 158 digital PROMs were implemented in skull base patients presenting for specialized outpatient consultations. Reduced personnel capacity led to significantly fewer PROMs being conducted during the second versus (vs.) the first year after introduction (mean: 0.77 vs. 2.47 per consultation day, p = 0.0002). The mean age of patients not completing vs. those completing long-term assessments was significantly higher (59.90 vs. 54.11 years, p = 0.0136). Follow-up response rates tended to be increased with recent surgery rather than with the wait-and-scan strategy. Our strategy of conducting digital PROMs appears suitable for assessing HRQoL in skull base diseases. The availability of medical personnel for implementation and supervision was essential. Response rates during follow-up tended to be higher both with younger age and after recent surgery.
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BACKGROUND: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (1) explore the prognostic utility of the classification system and (2) define how much removed non-CE tumor translates into a survival benefit. METHODS: The international RANO resect group retrospectively searched previously compiled databases from 7 neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and postoperative MRI were collected. RESULTS: We collected 1,008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC-26981/22981 (TMZ/RTâTMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with "maximal CE resection" (class 2) had superior outcome compared to patients with "submaximal CE resection" (class 3) or "biopsy" (class 4). Extensive resection of non-CE tumor (≤5 cm3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 ("supramaximal CE resection"). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. CONCLUSIONS: The proposed "RANO categories for extent of resection in glioblastoma" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such "supramaximal CE resection."
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Neoplasias Encefálicas , Glioblastoma , Humanos , Prognóstico , Glioblastoma/cirurgia , Glioblastoma/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Procedimentos Neurocirúrgicos , Resultado do TratamentoRESUMO
Graves' orbitopathy (GO) leads to increased orbital tissue and causes symptoms such as exophthalmos, functional complaints, or dysthyroid optic neuropathy. Different GO types with fat and/or muscle enlargement were identified, and increased muscle appears to particularly influence visual status and treatment response. The current study examines visual parameters dependent on orbital muscle volume fraction in a surgically treated GO cohort. After volumetric analysis of the preoperative orbital content, 83 orbits in 47 patients were categorized into predefined groups (increased or not-increased muscle fraction). All cases underwent pterional orbital decompression, and pre- and postoperative visual status was retrospectively analyzed. Forty-one orbits revealed increased and 42 orbits revealed not-increased muscle volume (mean fraction 29.63% versus (vs.) 15.60%). The preoperative visual acuity (VA) was significantly lower in orbits with increased vs. not-increased muscle volume (mean VA 0.30 vs. 0.53, difference 2.5 lines). After surgery, mean VA improved significantly by 1.7 lines in orbits with increased muscle volume. Not preoperative, but postoperative exophthalmos was significantly lower in orbits with not-increased muscle volume. Increased orbital muscle is associated with significantly reduced VA, but can be remarkably improved by pterional orbital decompression. Therefore, surgical therapy should be considered particularly in decreased VA with orbital muscle enlargement.
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Skull base cerebrospinal fluid (CSF) leaks can lead to severe complications and require appropriate diagnosis and treatment. Cisternography is applied when exact localization via conventional imaging is not successful. The present study is aimed at identifying factors with potential impact on radiological results and surgical success. Cisternography followed by surgical repair due to skull base CSF leaks was performed in 63 cases between 2002 and 2020. The clinical and radiological findings were analyzed retrospectively. The etiology of CSF leaks was traumatic in 30.2%, spontaneous in 36.5%, and iatrogenic in 33.3%. The sensitivity of cisternography was 87.9%. Spontaneous CSF leaks tended to be diagnosed less frequently via cisternography and were significantly less frequently localized intraoperatively. The median postoperative follow-up period was 34 months. The primary surgical success rate was 79.4%, with a significantly higher success rate for lateral than for anterior skull base defects. Surgical failure tended to be lower in iatrogenic and higher in traumatic defects. Cisternography proved to be a highly sensitive method to localize skull base CSF leaks and can be recommended for advanced diagnostics. Iatrogenic leaks seemed to be more likely to have a favorable surgical outcome, whereas traumatic leaks tended to have a lower surgical success rate.
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Endoscopia , Base do Crânio , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Vazamento de Líquido Cefalorraquidiano/cirurgia , Endoscopia/métodos , Humanos , Doença Iatrogênica , Estudos Retrospectivos , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Resultado do TratamentoRESUMO
Defects of the cranial vault often require cosmetic reconstruction with patient-specific implants, particularly in cases of craniofacial involvement. However, fabrication takes time and is expensive; therefore, efforts must be made to develop more rapidly available and more cost-effective alternatives. The current study investigated the feasibility of an augmented reality (AR)-assisted single-step procedure for repairing bony defects involving the facial skeleton and the skull base. In an experimental setting, nine neurosurgeons fabricated AR-assisted and conventionally shaped ("freehand") implants from polymethylmethacrylate (PMMA) on a skull model with a craniofacial bony defect. Deviations of the surface profile in comparison with the original model were quantified by means of volumetry, and the cosmetic results were evaluated using a multicomponent scoring system, each by two blinded neurosurgeons. Handling the AR equipment proved to be quite comfortable. The median volume deviating from the surface profile of the original model was low in the AR-assisted implants (6.40 cm3) and significantly reduced in comparison with the conventionally shaped implants (13.48 cm3). The cosmetic appearance of the AR-assisted implants was rated as very good (median 25.00 out of 30 points) and significantly improved in comparison with the conventionally shaped implants (median 14.75 out of 30 points). Our experiments showed outstanding results regarding the possibilities of AR-assisted procedures for single-step reconstruction of craniofacial defects. Although patient-specific implants still represent the gold standard in esthetic aspects, AR-assisted procedures hold high potential for an immediately and widely available, cost-effective alternative providing excellent cosmetic outcomes.
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Realidade Aumentada , Neurocirurgia , Procedimentos de Cirurgia Plástica , Craniotomia/métodos , Humanos , Próteses e Implantes , Procedimentos de Cirurgia Plástica/métodos , Crânio/cirurgia , Base do Crânio/cirurgiaRESUMO
Introduction: Petroclival meningioma (PCM) remains a major neurosurgical challenge. There are still controversial strategic treatment concepts about surgical approach, the extent of resection, and postoperative radiotherapy. We aimed to evaluate prognostic factors influencing the progression-free survival (PFS) rates of PCM, with a particular focus on the retrosigmoidal approach, the role of the extent of resection, and postoperative radiotherapy. Methods: Eighty-nine patients with complete follow-up data were included. All patients were operated on via a retrosigmoidal approach, of whom 19 underwent gross total resection (GTR) and 70 underwent subtotal resection (STR). In the subgroups of tumors with infiltration of the cavernous sinus, 41 patients received near total resection (NTR) and 24 STR. Thirty-one patients received postoperative radiotherapy of the residual tumor and 58 were treated with surgery alone. Kaplan-Meier analyses and Cox regression were used to identify significant factors associated with treatment. Results: GTR (p=0.0107) and postoperative radiotherapy (p=0.014) were associated with significantly improved PFS. Even the subgroup analysis of extended PCM with infiltration of the cavernous sinus (CS) showed an advantage for PFS after near total resection (NTR) (p=0.0017). The additional radiotherapy of the residual tumor in the CS in this subgroup also showed a beneficial effect on PFS (p=0.012). Conclusion: The extension of surgical resection remains the most important prognostic factor in relation to oncological outcomes. However, the GTR of extended PCM with infiltration of the CS is associated with significant neurological morbidity and requires additional adjuvant therapy concepts. Postoperative radiotherapy is an important element in the treatment of the residual tumor after surgery.
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OBJECT: The initial amount of subarachnoid and ventricular blood is an important prognostic factor for outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this comparative study of an unselected aSAH-population, we assess the modifiability of these factors by implementation of blood clearance by cisternal lavage. METHODS: All patients with aSAH treated in our department between October 2011 and October 2019 (8 years, n = 458) were included in our study. In the first 4-year period (BEFORE, n = 237), patients were treated according to international guidelines. In the second 4-year period (AFTER, n = 221), cisternal lavage methods were available and applied in 72 high-risk patients (32.5%). The cisternal and ventricular blood load was recorded by the Hijdra score. Multivariable regression models were used to assess the prognostic significance of risk factors, including blood load, in relation to common aSAH characteristics in both study groups. RESULTS: Worse neurological outcomes (mRS > 3) occurred in the BEFORE population with 41.45% versus 30.77% in the AFTER cohort, 6 months after aSAH (HR: 1.59, 95% CI 1.08-2.34, p = 0.01). Admission WFNS grade, comorbidities (Charlson Comorbidity Index), herniation signs, concomitant intracerebral hemorrhage, and the development of delayed cerebral infarction were strongly associated with poor outcome in both study groups. Intraventricular and cisternal blood load and, particularly, a cast fourth ventricle (Cast 4) represented strong prognosticators of poor neurological outcome in the BEFORE cohort. This effect was lost after implementation of cisternal lavage (AFTER cohort). CONCLUSION: Cisternal and ventricular blood load - in particular: a Cast 4 - represent important prognosticators in patients with aSAH. They are, however, amenable to modification by blood clearing therapies.
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Hemorragia Subaracnóidea , Infarto Cerebral/complicações , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/terapia , Irrigação Terapêutica/métodos , Resultado do TratamentoRESUMO
Spontaneous intracranial hypotension (SIH) is an orthostatic headache syndrome with typical MRI findings among which engorgement of the venous sinuses, pachymeningeal enhancement, and effacement of the suprasellar cistern have the highest diagnostic sensitivity. SIH is in almost all cases caused by spinal CSF leaks. Spinal MRI scans showing so-called spinal longitudinal extradural fluid (SLEC) are suggestive of ventral dural tears (type 1 leak) which are located with prone dynamic (digital subtraction) myelography. As around half of the ventral dural tears are located in the upper thoracic spine, additional prone dynamic CT myelography is often needed. Leaking nerve root sleeves typically associated with meningeal diverticulae (type 2 leaks) and CSF-venous fistulas (type 3 leaks) are proven via lateral decubitus dynamic digital subtraction or CT myelography: type 2 leaks are SLEC-positive if the tear is proximal and SLEC-negative if it is distal, and type 3 leaks are always SLEC-negative. Although 30-70% of SIH patients show marked improvement following epidural blood patches applied via various techniques definite cure mostly requires surgical closure of ventral dural tears and surgical ligations of leaking nerve root sleeves associated with meningeal diverticulae or CSF-venous fistulas. For the latter, transvenous embolization with liquid embolic agents via the azygos vein system is a novel and valuable therapeutic alternative.
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Hipotensão Intracraniana , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Vazamento de Líquido Cefalorraquidiano/terapia , Humanos , Hipotensão Intracraniana/diagnóstico por imagem , Hipotensão Intracraniana/terapia , Imageamento por Ressonância Magnética , Mielografia , Coluna VertebralRESUMO
Proton magnetic resonance spectroscopy (1H-MRS) delivers information about the non-invasive metabolic landscape of brain pathologies. 1H-MRS is used in clinical setting in addition to MRI for diagnostic, prognostic and treatment response assessments, but the use of this radiological tool is not entirely widespread. The importance of developing automated analysis tools for 1H-MRS lies in the possibility of a straightforward application and simplified interpretation of metabolic and genetic data that allow for incorporation into the daily practice of a broad audience. Here, we report a prospective clinical imaging trial (DRKS00019855) which aimed to develop a novel MR-spectroscopy-based algorithm for in-depth characterization of brain lesions and prediction of molecular traits. Dimensional reduction of metabolic profiles demonstrated distinct patterns throughout pathologies. We combined a deep autoencoder and multi-layer linear discriminant models for voxel-wise prediction of the molecular profile based on MRS imaging. Molecular subtypes were predicted by an overall accuracy of 91.2% using a classifier score. Our study indicates a first step into combining the metabolic and molecular traits of lesions for advancing the pre-operative diagnostic workup of brain tumors and improve personalized tumor treatment.
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Craniopharyngiomas are typically located in the sellar region and frequently contain space-occupying cysts. They usually cause visual impairment and endocrine disorders. Due to the high potential morbidity associated with radical resection, several less invasive surgical approaches have been developed. This study investigated stereotactic-guided implantation of cysto-ventricular catheters (CVC) as a new method to reduce and control cystic components. Twelve patients with cystic craniopharyngiomas were treated with CVC in our hospital between 04/2013 and 05/2017. The clinical and radiological data were retrospectively analysed to evaluate safety aspects as well as ophthalmological and endocrine symptoms. The long-term development of tumour and cyst volumes was assessed by volumetry. The median age of our patients was 69.0 years and the median follow-up period was 41.0 months. Volumetric analyses demonstrated a mean reduction of cyst volume of 64.2% after CVC implantation. At last follow-up assessment, there was a mean reduction of cyst volume of 92.0% and total tumour volume of 85.8% after completion of radiotherapy. Visual acuity improved in 90% of affected patients, and visual field defects improved in 70% of affected patients. No patient showed ophthalmological deterioration after surgery, and endocrine disorders remained stable. Stereotactic implantation of CVC proved to be a safe minimally invasive method for the long-term reduction of cystic components with improved ophthalmological symptoms. The consequential decrease of total tumour volumes optimised conditions for adjuvant radiotherapy. Given the low surgical morbidity and the effective drainage of tumour cysts, this technique should be considered for the treatment of selected cystic craniopharyngiomas.