MILENA SALES PITOMBEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- 11C-PK11195 plasma metabolization has the same rate in multiple sclerosis patients and healthy controls: a cross-sectional study(2021) SOUZA, Aline Morais de; PITOMBEIRA, Milena Sales; SOUZA, Larissa Estessi de; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; REAL, Caroline Cristiano; FARIA, Daniele de Paula11C-PK11195 is a positron emitter tracer used for Positron Emission Tomography (PET) imaging of innate immune cell activation in studies of neuroinflammatory diseases. For the image quantitative analysis, it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition (plasma intact fraction). Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition. The purpose of this study is to compare 11C-PK11195 plasma metabolization rate between healthy controls and multiple sclerosis (MS) patients and evaluate the interference of sex, age, treatment, and disease phenotype in the tracer intact fraction measured in arterial plasma samples. 11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients (n = 50) and healthy controls (n = 23) at 20, 45, and 60 minutes after 11C-PK11195 injection. Analyses were also stratified by sex, age, treatment type, and MS phenotype. The results showed no significant differences in the metabolization rate of healthy controls and MS patients, or in the stratified samples. In conclusion, 11C-PK11195 metabolization has the same rate in patients with MS and healthy controls, which is not affected by sex, age, treatment, and disease phenotype. Thus, these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition, by using a population metabolization rate average. The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School (approval No. 624.065) on April 23, 2014.
- The challenges of monitoring neurological manifestations associated with COVID-19 in Latin America: does the World Health Organization need changes?(2020) MENDES, Maria Fernanda; PITOMBEIRA, Milena Sales; DIAS-CARNEIRO, Rafael Paterno Castello; FERREIRA, Lis Campos; MARTINS, Gabriela Joca; BRUM, Doralina Guimaraes
- Long-term safety of azathioprine for treatment of neuromyelitis optica spectrum disorders(2021) GOMES, Ana Beatriz Ayroza Galvao Ribeiro; PITOMBEIRA, Milena Sales; SATO, Douglas Kazutoshi; CALLEGARO, Dagoberto; APOSTOLOS-PEREIRA, Samira LuisaBackground: Azathioprine is a common first-line therapy for neuromyelitis optica spectrum disorder (NMOSD). Objective: The aim of this study was to determine whether long-term treatment (>10 years) with azathioprine is safe in NMOSD. Methods: We conducted a retrospective medical record review of all patients at the School of Medicine of the University of Sao Paulo (Sao Paulo, Brazil) who fulfilled the 2015 international consensus diagnostic criteria for NMOSD and were treated with azathioprine for at least 10 years. Results: Out of 375 patients assessed for eligibility, 19 were included in this analysis. These patients' median age was 44 years (range=28-61); they were mostly female (17/19) and AQP4-IgG seropositive (18/19). The median disease duration was 15 years (range=10-39) and most patients presented a relapsing clinical course (84.2%). The median duration of treatment was 11.9 years (range=10.0-23.8). The median annualized relapse rates (ARR) pre- and post-treatment with azathioprine were 1 (range=0.1 2) and 0.1 (range=0-0.35); p=0.09. Three patients (15.7%) had records of adverse events during the follow-up, which consisted of chronic B12 vitamin deficiency, pulmonary tuberculosis and breast cancer. Conclusion: Azathioprine may be considered a safe agent for long-term treatment (>10 years) of NMOSD, but continuous vigilance for infections and malignancies is required.
- The effect of lesion filling on brain network analysis in multiple sclerosis using structural magnetic resonance imaging(2022) WEIJDEN, Chris W. J. van der; PITOMBEIRA, Milena S.; HAVEMAN, Yudith R. A.; SANCHEZ-CATASUS, Carlos A.; CAMPANHOLO, Kenia R.; KOLINGER, Guilherme D.; RIMKUS, Carolina M.; BUCHPIGUEL, Carlos A.; DIERCKX, Rudi A. J. O.; RENKEN, Remco J.; MEILOF, Jan F.; VRIES, Erik F. J. de; FARIA, Daniele de PaulaBackground Graph theoretical network analysis with structural magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients can be used to assess subtle changes in brain networks. However, the presence of multiple focal brain lesions might impair the accuracy of automatic tissue segmentation methods, and hamper the performance of graph theoretical network analysis. Applying ""lesion filling"" by substituting the voxel intensities of a lesion with the voxel intensities of nearby voxels, thus creating an image devoid of lesions, might improve segmentation and graph theoretical network analysis. This study aims to determine if brain networks are different between MS subtypes and healthy controls (HC) and if the assessment of these differences is affected by lesion filling. Methods The study included 49 MS patients and 19 HC that underwent a T1w, and T2w-FLAIR MRI scan. Graph theoretical network analysis was performed from grey matter fractions extracted from the original T1w-images and T1w-images after lesion filling. Results Artefacts in lesion-filled T1w images correlated positively with total lesion volume (r = 0.84, p < 0.001) and had a major impact on grey matter segmentation accuracy. Differences in sensitivity for network alterations were observed between original T1w data and after application of lesion filling: graph theoretical network analysis obtained from lesion-filled T1w images produced more differences in network organization in MS patients. Conclusion Lesion filling might reduce variability across subjects resulting in an increased detection rate of network alterations in MS, but also induces significant artefacts, and therefore should be applied cautiously especially in individuals with higher lesions loads.
- Evaluation of Non-Invasive Methods for (R)-[11C]PK11195 PET Image Quantification in Multiple Sclerosis(2024) MANTOVANI, Dimitri B. A.; PITOMBEIRA, Milena S.; SCHUCK, Phelipi N.; ARAUJO, Adriel S. de; BUCHPIGUEL, Carlos Alberto; FARIA, Daniele de Paula; SILVA, Ana Maria M. daThis study aims to evaluate non-invasive PET quantification methods for (R)-[C-11]PK11195 uptake measurement in multiple sclerosis (MS) patients and healthy controls (HC) in comparison with arterial input function (AIF) using dynamic (R)-[C-11]PK11195 PET and magnetic resonance images. The total volume of distribution (VT) and distribution volume ratio (DVR) were measured in the gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, cerebellum, and brainstem using AIF, the image-derived input function (IDIF) from the carotid arteries, and pseudo-reference regions from supervised clustering analysis (SVCA). Uptake differences between MS and HC groups were tested using statistical tests adjusted for age and sex, and correlations between the results from the different quantification methods were also analyzed. Significant DVR differences were observed in the gray matter, white matter, putamen, pallidum, thalamus, and brainstem of MS patients when compared to the HC group. Also, strong correlations were found in DVR values between non-invasive methods and AIF (0.928 for IDIF and 0.975 for SVCA, p < 0.0001). On the other hand, (R)-[C-11]PK11195 uptake could not be differentiated between MS patients and HC using VT values, and a weak correlation (0.356, p < 0.0001) was found between VTAIF and VTIDIF. Our study shows that the best alternative for AIF is using SVCA for reference region modeling, in addition to a cautious and appropriate methodology.
- Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia(2023) NOBREGA, Paulo R.; PAIVA, Anderson R. B. de; SOUZA, Katiane S.; SOUZA, Jorge Luiz B. de; LIMA, Pedro Lucas G. S. B.; SILVA, Delson Jose da; PITOMBEIRA, Milena Sales; BORGES, Viviennee K.; DIAS, Daniel A.; BISPO, Luciana M.; SANTOS, Carolina F.; FREUA, Fernando; SILVA, Paulo Diego S.; ALVES, Isabela S.; PORTELLA, Leonardo B.; CUNHA, Paulina R.; SALOMAO, Rubens Paulo A.; PEDROSO, Jose Luiz; MIYAJIMA, Veridiana P.; MIYAJIMA, Fabio; CALI, Elisa; WADE, Charles; SUDARSANAM, Annapurna; O'DRISCOLL, Mary; HAYTON, Tom; BARSOTTINI, Orlando G. P.; KLEBE, Stephan; KOK, Fernando; LUCATO, Leandro Tavares; HOULDEN, Henry; DEPIENNE, Christel; LYNCH, David S.; BRAGA-NETO, PedroMutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay. Nobrega et al. describe 12 additional CLCN2 leucoencephalopathy patients expanding the phenotypic spectrum by adding prominent seizures, severe spastic paraplegia and developmental delay. All patients demonstrated typical MRI changes. They found three novel missense variants. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy. Graphical abstract