MILENA SALES PITOMBEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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- 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.
- Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study(2022) PITOMBEIRA, Milena Sales; KOOLE, Michel; CAMPANHOLO, Kenia R.; SOUZA, Aline M.; DURAN, Fabio L. S.; SOLLA, Davi J. Fontoura; MENDES, Maria F.; PEREIRA, Samira L. Apostolos; RIMKUS, Carolina M.; BUSATTO, Geraldo Filho; CALLEGARO, Dagoberto; BUCHPIGUEL, Carlos A.; FARIA, Daniele de PaulaPurpose Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. Methods We used the 18-kDa translocator protein (TSPO) tracer (R)[C-11]PK11195 and [C-11]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)[C-11]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [C-11]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). Results In the VOI-based analysis, [C-11]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[C-11]PK11195 V-T were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[C-11]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [C-11]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[C-11]PK11195 V-T and lower [C-11]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T-2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [C-11]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[C-11]PK11195 V-T (P = 0.013). Conclusions Widespread innate immune cells profile and marked loss of myelin in T-2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures.
- Clinical Features and Inflammatory Markers in Autoimmune Encephalitis Associated With Antibodies Against Neuronal Surface in Brazilian Patients(2019) NOBREGA, Paulo Ribeiro; PITOMBEIRA, Milena Sales; MENDES, Lucas Silvestre; KRUEGER, Mariana Braatz; SANTOS, Carolina Figueiredo; MORAIS, Norma Martins de Menezes; SIMABUKURO, Mateus Mistieri; MAIA, Fernanda Martins; BRAGA-NETO, PedroAcute encephalitis is a debilitating neurological disorder associated with brain inflammation and rapidly progressive encephalopathy. Autoimmune encephalitis (AE) is increasingly recognized as one of the most frequent causes of encephalitis, however signs of inflammation are not always present at the onset which may delay the diagnosis. We retrospectively assessed patients with AE associated with antibodies against neuronal surface diagnosed in reference centers in Northeast of Brazil between 2014 to 2017. CNS inflammatory markers were defined as altered CSF (pleocytosis >5 cells/mm(3)) and/or any brain parenchymal MRI signal abnormality. Thirteen patients were evaluated, anti-NMDAR was the most common antibody found (10/13, 77%), followed by anti-LGI1 (2/13, 15%), and anti-AMPAR (1/13, 7%). Median time to diagnosis was 4 months (range 2-9 months). Among these 13 patients, 6 (46.1%) had inflammatory markers and when compared to those who did not present signs of inflammation, there were no significant differences regarding the age of onset, time to diagnosis and modified Rankin scale score at the last visit. Most of the patients presented partial or complete response to immunotherapy during follow-up. Our findings suggest that the presence of inflammatory markers may not correlate with clinical presentation or prognosis in patients with AE associated with antibodies against neuronal surface. Neurologists should be aware to recognize clinical features of AE and promptly request antibody testing even without evidence of inflammation in CSF or MRI studies.
conferenceObject Generating PET-derived maps of myelin content from clinical MRI using Generative Adversarial Networks(2023) SOULIER, Theodore; HAMZAOUI, Mariem; PITOMBEIRA, Milena Sales; FARIA, Daniele; YAZDAN-PANAH, Arya; TONIETTO, Matteo; BOTTLAENDER, Michel; LEROY, Claire; BODINI, Benedetta; AYACHE, Nicholas; COLLIOT, Olivier; STANKOFF, Bruno- Persistent MOG-IgG positivity is a predictor of recurrence in MOG-IgG-associated optic neuritis, encephalitis and myelitis(2019) OLIVEIRA, Luana Michelli; APOSTOLOS-PEREIRA, Samira Luisa; PITOMBEIRA, Milena Sales; TORRETTA, Pedro Henrique Bruel; CALLEGARO, Dagoberto; SATO, Douglas KazutoshiBackground: MOG-IgG-associated optic neuritis, encephalitis and myelitis (MONEM) is a recently recognized group of inflammatory central nervous system (CNS) disorders distinct from multiple sclerosis and neuromyelitis optica spectrum disorders. Limited data are available regarding the predictors of relapse in this condition. Objective: We aimed to evaluate the longitudinal serostatus of patients with MOG-IgG and to correlate serostatus with long-term clinical outcomes. Methods: Of 574 consecutive patients who presented with demyelinating inflammatory CNS disorders, we included 31 patients who were MOG-IgG-positive. Patients with MOG-IgG were followed up from 2011 to 2017 at the School of Medicine, University of SAo Paulo, Brazil. Results: Relapsing disease occurred in 23 out of 31 patients (74%), while 8 (26%) exhibited a monophasic course. All monophasic patients, as well as the majority of relapsing patients, became seronegative during clinical remission. Patients exhibiting disease activity in the last 2years were more likely to remain positive, with higher medium titres than those found in patients in clinical remission. Conclusion: MOG-IgG patients usually present with a relapsing course, and the risk of relapse was associated with longitudinally persistent MOG-IgG seropositivity. In contrast, patients who experienced a single attack became spontaneously seronegative for MOG-IgG during long-term follow-up.
- 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.
bookPart Espectro da neuromielite óptica (doença de Devic)(2021) PEREIRA, Samira Luisa dos Apóstolos; PITOMBEIRA, Milena Sales; CALLEGARO, Dagoberto- 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