DAGOBERTO CALLEGARO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
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- 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.
- The protective effects of high-education levels on cognition in different stages of multiple sclerosis(2018) RIMKUS, Carolina de Medeiros; AVOLIO, Isabella Maria Bello; MIOTTO, Eliane Correa; PEREIRA, Samira Apostolos; MENDES, Maria Fernanda; CALLEGARO, Dagoberto; LEITE, Claudia da CostaBackground: Low-education attainment is associated with worse cognitive performance in multiple sclerosis (MS) patients, and possibly with a lower cognitive reserve and/or increased inflammatory activity. Cognitive reserve refers to the capability of a source of intellectual enrichment in attenuating a negative effect of a diseaserelated factor; while the inflammatory activity is often related to T2-lesion load (T2-LL) increase. Objective: To disentangle the effects of cognitive reserve and an increased T2-LL in MS-patients with low-education levels. Methods: The study included 136 MS patients and 65 healthy-controls, divided in low-education (12 years or less of school education without obtaining any technical superior degree) and high-education (more than 12 years of school education with technical or superior degree) groups. An extensive battery of neuropsychological tests was applied examining intelligence quotient and six cognitive domains. Test results were z-scored and subjects with z-scores <= -1.5 in two or more domains were considered cognitively impaired. To test the factors associated with worse cognitive performance, regression models were applied using average cognition as target; education level, Expanded Disability Status Scale (EDSS), T2-LL, disease duration, age of disease onset, age and gender as predictors. We also tested the correlation between T2-LL and cognition in the groups. To investigate the role of education level as a source of intellectual enrichment/cognitive reserve in different stages of MS, we sub-divided the MS patients in three groups according to the disease duration (less than 5 years, between 5 and 10 years and more than 10 years). Results: Worse average cognition was associated with low-education level, higher T2-LL and male gender. A higher frequency of cognitively impaired patients was observed in MS patients with low-education level, in all stages of the disease. In patients with a disease duration shorter than five years, there was a lower correlation between worse average cognition and T2-LL in the high-education level group, compared to the patients with low-education level; in MS patients with longer disease duration, we observed a stronger correlation between lesion burden and cognitive impairment in both groups. Conclusion: Education attainment is a source of intellectual enrichment and can enhance the cognitive reserve in MS patients. The protective effect of a high-education level was stronger in patients with less than five years of disease, suggesting a stronger role of cognitive reserve in short-term disease. In long-term disease we observed a greater impact of increased inflammatory activity on cognition.
- Primary angiitis of the central nervous system as a mimic of multiple sclerosis: A case report(2022) TIEPPO, Eduardo Macedo de Souza; SILVA, Tomas Fraga Ferreira da; ARAUJO, Roger Santana; SILVA, Guilherme Diogo; PAES, Vitor Ribeiro; RIMKUS, Carolina de Medeiros; TINONE, Gisela; PEREIRA, Samira Apostolos; CALLEGARO, DagobertoBackground: Primary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis. Case presentation: A 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization. Discussion: Our patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging. Conclusion: The presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis.
- Real-world application of the 2022 diagnostic criteria for first-ever episode of optic neuritis(2023) TERRIM, Sara; SILVA, Guilherme Diogo; FALCAO, Fernando Cavalcanti de Sa e Benevides; PEREIRA, Clarissa dos Reis; BENASSI, Thais de Souza Andrade; FORTINI, Ida; GONCALVES, Marcia Rubia Rodrigues; CASTRO, Luiz Henrique Martins; COMERLATTI, Luiz Roberto; RIMKUS, Carolina de Medeiros; ADONI, Tarso; PEREIRA, Samira Luisa Apostolos; MONTEIRO, Mario Luiz; CALLEGARO, DagobertoOptic neuritis (ON) admits diverse differential diagnoses. Petzold proposed diagnostic criteria for ON in 2022, although real-world application of these criteria is missing. We conducted a retrospective review of patients with ON. We classified patients into definite or possible ON, and into groups A (typical neuritis), B (painless), or C (binocular) and estimated the frequency of etiologies for each group. We included 77 patients, with 62% definite and 38% possible ON. CRION and NMOSD-AQP4 negative-ON were less commonly seen in definite ON. Application of the 2022 criteria revealed a lower-than-expected frequency of definite ON, particularly for seronegative non-MS causes.
- Myelin imaging measures as predictors of cognitive impairment in MS patients: A hybrid PET-MRI study(2022) CAMPANHOLO, K. R.; PITOMBEIRA, M. S.; RIMKUS, C. M.; MENDES, M. F.; APOSTOLOS-PEREIRA, S. L.; BUSATTO FILHO, G.; CALLEGARO, D.; BUCHPIGUEL, C. A.; DURAN, F. L. S.; FARIA, D. De PaulaBackground: Cognitive impairment is one of the concerns of Multiple Sclerosis (MS) and has been related to myelin loss. Different neuroimaging methods have been used to quantify myelin and relate it to cognitive dysfunctions, among them Magnetization Transfer Ratio (MTR), Diffusion Tensor Imaging (DTI), and, more recently, Positron Emission Tomography (PET) with C-11-PIB. Objective: To investigate different myelin imaging modalities as predictors of cognitive dysfunction. Methods: Fifty-one MS patients and 24 healthy controls underwent clinical and neuropsychological assessment and MTR, DTI (Axial Diffusion-AD and Fractional Anisotropy-FA maps), and C-11-PIB PET images in a PET/MR hybrid system. Results: MTR and DTI(FA) differed in patients with or without cognitive impairment. There was an association of DTI(FA) and DTI(AD) with cognition and psychomotor speed for progressive MS, and of C-11-PIB uptake and MTR for relapsing-remitting MS. MTR in the Thalamus (beta=-0.51, p=0.021) and Corpus Callosum (beta=-0.24, p=0.033) were predictive of cognitive impairment. DTI-FA in the Caudate (beta=-26.93, p=0.006) presented abnormal predictive result. Conclusion: Lower myelin content by C-11-PIB uptake was associated with worse cognitive status. MTR was predictive of cognitive impairment in MS.
- Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study(2023) TIEPPO, Eduardo Macedo de Souza; SILVA, Guilherme Diogo; SILVA, Tomas Fraga Ferreira da; ARAUJO, Roger Santana de; OLIVEIRA, Mateus Boaventura de; SPRICIGO, Mariana Gondim Peixoto; PIMENTEL, Gabriela Almeida; CAMPANA, Igor Gusmao; CASTRILLO, Bruno Batitucci; MENDES, Natalia Trombini; TEIXEIRA, Larissa Silva; NUNES, Douglas Mendes; RIMKUS, Carolina de Medeiros; ADONI, Tarso; PEREIRA, Samira Luisa Apostolos; CALLEGARO, DagobertoBackground: Multiple sclerosis misdiagnosis remains a problem despite the well-validated McDonald 2017. For proper evaluation of errors in the diagnostic process that lead to misdiagnosis, it is adequate to incorporate patients who are already under regular follow-up at reference centers of demyelinating diseases. Objectives: To evaluate multiple sclerosis misdiagnosis in patients who are on follow-up at a reference center of demyelinating diseases in Brazil. Methods: We designed an observational study including patients in regular follow-up, who were diagnosed with multiple sclerosis at our specialized outpatient clinic in the Hospital of Clinics in the University of Sao Paulo, from 1996 to 2021, and were reassessed for misdiagnosis in 2022. We evaluated demographic information, clinical profile, and complementary exams and classified participants as ""established multiple sclerosis,"" ""non-multiple sclerosis, diagnosed,"" and ""non-multiple sclerosis, undiagnosed."" Failures in the diagnostic process were assessed by the modified Diagnostic Error Evaluation and Research tool. Results: A total of 201 patients were included. After analysis, 191/201 (95.02%) participants were confirmed as ""established multiple sclerosis,"" 5/201 (2.49%) were defined as ""non-multiple sclerosis, diagnosed,"" and 5/201 (2.49%) were defined as ""non-multiple sclerosis, undiagnosed."" Conclusions: Multiple sclerosis misdiagnosis persists in reference centers, emphasizing the need for careful interpretation of clinical findings to prevent errors.