Decreased cerebral glucose metabolism in patients with brain tumors: an effect of corticosteroids

1995 ◽  
Vol 83 (4) ◽  
pp. 657-664 ◽  
Author(s):  
Michael J. Fulham ◽  
Arturo Brunetti ◽  
Luigi Aloj ◽  
Ramesh Raman ◽  
Andrew J. Dwyer ◽  
...  

✓ The authors measured cerebral glucose metabolism (CMRglu) using [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in patients with brain tumors to evaluate the effect of exogenous corticosteroids (in this instance, dexamethasone) on glucose metabolism. Fifty-six FDG-PET studies obtained in 45 patients with unilateral supratentorial brain tumors were analyzed. Patients with brain tumors were divided into three groups: 1) patients with cushingoid symptoms, who had been treated with combinations of radiotherapy and chemotherapy taking oral dexamethasone; 2) patients not taking dexamethasone but treated with radiotherapy; and 3) patients not taking dexamethasone who had not been treated with radiotherapy. Serial FDG-PET scans were obtained in eight of the cushingoid patients. Glucose metabolism was measured in the contralateral cerebral and ipsilateral cerebellar hemispheres in patients and compared to measurements taken from 19 normal volunteers. The authors found that in the cushingoid brain tumor patients there was a marked reduction in CMRglu compared to normal volunteers and other brain tumor patients (Kruskal—Wallis test; p 0.001). In the majority of patients who had serial FDG-PET scans, there was a decline in glucose metabolism over time and in one patient, in whom dexamethasone was reduced in dosage, there was a subsequent increase in CMRglu. The authors conclude that there is a generalized reduction in CMRglu in brain tumor patients taking dexamethasone compared to other brain tumor patients and normal volunteers, and that this effect is independent of radiotherapy, concurrent anticonvulsant medication, and transhemispheric functional disconnection (transhemispheric diaschisis).

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Julien Delrieu ◽  
Thierry Voisin ◽  
Laure Saint-Aubert ◽  
Isabelle Carrie ◽  
Christelle Cantet ◽  
...  

Abstract Background The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism. Methods MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to “MI group” or “No MI group.” The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months, and 12 months, and cerebral magnetic resonance imaging scans at baseline. The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis. Results The intention-to-treat population included 67 subjects (34 in the MI group and 33 in the No MI group. No significant MI effect was observed on primary outcome at 6 months. In the exploratory voxel-wise analysis, we observed a difference in favor of MI group on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months. Conclusions MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression. Trial registration ClinicalTrials.gov Identifier, NCT01513252.


2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.


1984 ◽  
Vol 61 (6) ◽  
pp. 1085-1090 ◽  
Author(s):  
Kenji Kikuchi ◽  
Christopher I. McCormick ◽  
Edward A. Neuwelt

✓ This investigation was conducted to examine the immunosuppressive potential of phenytoin in vivo and to document a correlation between phenytoin therapy and depressed lymphocyte responsiveness to mitogens. It was thought that phenytoin, the most widely used anticonvulsant agent, may play some role in the immunosuppression seen in brain-tumor patients. The effect of phenytoin on mitogen-stimulated lymphocyte function was evaluated by tritiated (3H)-thymidine incorporation and lymphocyte nuclear size distribution. Lymphocytes from either phenytoin-treated or normal rabbits were incubated for 90 hours in culture medium in the presence of three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). Significant suppression of mitogen-induced activation of the lymphocytes from treated animals was demonstrated. The present studies suggest a possible connection between phenytoin therapy and altered immune competence in brain-tumor patients.


1992 ◽  
Vol 15 ◽  
pp. 544A-545A
Author(s):  
Y. SAMSON ◽  
P. De MOLINER ◽  
M. OTTAVIANI ◽  
B. MAZIERE

1993 ◽  
Vol 11 (11) ◽  
pp. 2101-2111 ◽  
Author(s):  
R L Wahl ◽  
K Zasadny ◽  
M Helvie ◽  
G D Hutchins ◽  
B Weber ◽  
...  

PURPOSE We assessed the feasibility of noninvasive metabolic monitoring of cancer chemohormonotherapy using sequential quantitative positron emission tomographic (PET) scans of tumor glucose metabolism with the glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS Eleven women with newly diagnosed primary breast cancers larger than 3 cm in diameter beginning a chemohormonotherapy program underwent a baseline and four follow-up quantitative PET scans during the first three cycles of treatment (days 0 to 63). Tumor response was sequentially determined clinically, radiographically, and then pathologically after nine treatment cycles. RESULTS Eight patients had partial or complete pathologic responses. Their maximal tumor uptake of FDG assessed by PET decreased promptly with treatment to the following: day 8, 78 +/- 9.2% (P < .03); day 21, 68.1 +/- 7.5% (P < .025); day 42, 60 +/- 5.1% (P < .001); day 63, 52.4 +/- 4.4% (P < .0001) of the basal values. Tumor diameter did not decrease significantly during this period through 63 days. Prompt decreases in the FDG influx rate (K) from basal levels (from .019 to .014 mL/cm3/min) after 8 days of treatment (P < .02) and in the estimated rate of FDG phosphorylation to FDG-6-phosphate (k3) from .055 to .038 min-1 after 8 days of treatment (P < .02) to .029 +/- .004 min-1 at 21 days) (P < .02) were observed. Three nonresponding patients had no significant decrease in tumor uptake of FDG (81 +/- 18% of basal value), influx rate (.015 to .012 mL/cm3/min), or tumor size (81 +/- 12% of basal diameter) comparing basal versus 63-day posttreatment values. CONCLUSION Quantitative FDG PET scans of primary breast cancers showed a rapid and significant decrease in tumor glucose metabolism after effective treatment was initiated, with the reduction in metabolism antedating any decrement in tumor size. No significant decrease in FDG uptake (SUV) after three cycles of treatment was observed in the nonresponding patients. FDG PET scanning has substantial promise as an early noninvasive metabolic marker of the efficacy of cancer treatment.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1546 ◽  
Author(s):  
Alena Kopkova ◽  
Jiri Sana ◽  
Tana Machackova ◽  
Marek Vecera ◽  
Lenka Radova ◽  
...  

Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.


2019 ◽  
Vol 12 (4) ◽  
pp. 466-480
Author(s):  
Li Na ◽  
Xiong Zhiyong ◽  
Deng Tianqi ◽  
Ren Kai

Purpose The precise segmentation of brain tumors is the most important and crucial step in their diagnosis and treatment. Due to the presence of noise, uneven gray levels, blurred boundaries and edema around the brain tumor region, the brain tumor image has indistinct features in the tumor region, which pose a problem for diagnostics. The paper aims to discuss these issues. Design/methodology/approach In this paper, the authors propose an original solution for segmentation using Tamura Texture and ensemble Support Vector Machine (SVM) structure. In the proposed technique, 124 features of each voxel are extracted, including Tamura texture features and grayscale features. Then, these features are ranked using the SVM-Recursive Feature Elimination method, which is also adopted to optimize the parameters of the Radial Basis Function kernel of SVMs. Finally, the bagging random sampling method is utilized to construct the ensemble SVM classifier based on a weighted voting mechanism to classify the types of voxel. Findings The experiments are conducted over a sample data set to be called BraTS2015. The experiments demonstrate that Tamura texture is very useful in the segmentation of brain tumors, especially the feature of line-likeness. The superior performance of the proposed ensemble SVM classifier is demonstrated by comparison with single SVM classifiers as well as other methods. Originality/value The authors propose an original solution for segmentation using Tamura Texture and ensemble SVM structure.


1986 ◽  
Vol 4 (8) ◽  
pp. 1262-1269 ◽  
Author(s):  
P J O'Dwyer ◽  
S A King ◽  
C L Fortner ◽  
B Leyland-Jones

An analysis of hypersensitivity reactions to teniposide was approached using three methods: investigator survey, adverse drug reaction analysis, and literature search. By the survey method, hypersensitivity incidence was 6.5% with the majority of the reactions (82%) occurring in brain tumor or neuroblastoma patients. By the second method, 43 cases of hypersensitivity that were reported to the National Cancer Institute (NCI) between January 1983 and October 1985 were analyzed in detail. Reaction onset was unpredictable according to the number of drug doses. The majority of the patients (65%) experiencing the reaction had neuroblastoma or brain tumors, and these patients also tended to react earlier in the course of drug administration than those with hematologic malignancies. Clinical presentation was not correlated with the patient's diagnosis. All patients recovered. However, only six of 13 were successfully rechallenged with the drug. The third approach, the literature search, provided information on 82 hypersensitivity reactions among 2,250 patients (3.6% incidence). Forty-five percent of these reactions were linked to neuroblastoma or brain tumor patients. The analysis of hypersensitivity to teniposide by these three methods provides insight into the true incidence of hypersensitivity reactions in the general patient population. The frequency of the reactions is substantially higher in patients with neuroblastoma and brain tumors. This population should be considered for future trials of aggressive prophylactic therapy.


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