DAGOBERTO CALLEGARO

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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

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Autor e Coautores FMUSP-HC Normalizados: SAMIRA LUISA DOS APOSTOLOS PEREIRA × Categoria: original article × Tipo de acesso: restrictedAccess ×

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Agora exibindo 1 - 10 de 26
  • article 47 Citação(ões) na Scopus
    Cerebrospinal Fluid Aquaporin-4 Antibody Levels in Neuromyelitis Optica Attacks
    (2014) SATO, Douglas Kazutoshi; CALLEGARO, Dagoberto; JORGE, Frederico M. de Haidar; NAKASHIMA, Ichiro; NISHIYAMA, Shuhei; TAKAHASHI, Toshiyuki; SIMM, Renata Faria; APOSTOLOS-PEREIRA, Samira Luisa; MISU, Tatsuro; STEINMAN, Lawrence; AOKI, Masashi; FUJIHARA, Kazuo
    To elucidate immunopathogenetic roles of aquaporin-4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin-4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin-4 antibody seropositive patients. The CSF aquaporin-4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin-6 that can regulate antibody-producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin-4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks.
  • article 16 Citação(ões) na Scopus
    Characterization of pain syndromes in patients with neuromyelitis optica
    (2020) VALERIO, Fernanda; APOSTOLOS-PEREIRA, Samira L.; SATO, Douglas Kazutoshi; CALLEGARO, Dagoberto; LUCATO, Leandro Tavares; BARBOZA, Victor Rosseto; SILVA, Valquiria A.; GALHARDONI, Ricardo; RODRIGUES, Antonia L. de Lima; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi de
    Background Pain is common and refractory in spinal cord injury (SCI). Currently, most studies evaluated pain in male-predominant traumatic-SCI. Also, concomitant secondary pain syndromes and its temporal evolution were seldom reported. Methods We aimed to prospectively describe the main and secondary pain and its associated factors in inflammatory-SCI evaluating neuromyelitis optica (NMO) patients. In-remission NMO patients underwent neurological, imaging and autoantibody evaluations. Questionnaires detailing main and secondary pains, functional state, mood, catastrophizing, quality of life (QoL) and ""non-motor symptoms"" were used at two time points. Results Pain was present in 53 (73.6%) of the 72 patients included. At-level neuropathic pain was the most common main pain syndrome, affecting 32 subjects (60.4% of those with pain). Over 70% (n = 38) of this cohort reported two pain syndromes. Those without pain were significantly younger (26.1 +/- 12.7 y.o. in those without pain and 40.1 +/- 12.5, 37.2 +/- 11.4 y.o. in those whose main pain was neuropathic and non-neuropathic, respectively,p = .001), and no differences in the inflammatory status were observed between groups. On follow-up, one-fifth (n = 11) had a different main pain syndrome from the first visit. Pain impacted QoL as much as disability and motor strength. Conclusion Pain is a prevalent and disabling non-motor symptom in NMO-SCI. Most patients experience more than one pain syndrome which can change in time even in the absence of clinical relapse. Age of the inflammatory-SCI was a major determinant of pain. Acknowledging temporal changes and multiplicity of pain syndromes in NMO-SCI may give insights into more precise designs of clinical trials and general management of pain in SCI. Significance In this longitudinal study with NMO-related SCI, pain affected almost three-quarters of patients with NMO. Over 70% have more than one pain syndrome and at-level neuropathic pain is the most common type of pain syndrome. Patients without pain were significantly younger but had the same burden of inflammatory lesions than those with pain. During follow-up, up to one fifth of patients presented with changes in the main pain syndromes, which can occur even in the absence of clinical activity of the inflammatory disease. In this cohort, Pain affected quality of life as much as disability or motor strength.
  • article 4 Citação(ões) na Scopus
    Asymptomatic MRI lesions in pediatric-onset AQP4-IgG positive NMOSD
    (2022) PAOLILO, Renata Barbosa; RIMKUS, Carolina de Medeiros; PAZ, Jose Albino da; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, Dagoberto; SATO, Douglas Kazutoshi
    Background and purpose: Around 5% of all Neuromyelitis Optica Spectrum Disorders (NMOSD) cases start before 18 years of age. Clinical and radiological manifestations of AQP4-IgG positive NMOSD were revised in 2015, and the importance of neuroimaging in the diagnosis is well recognized. Neuroimaging findings in pediatric-onset NMOSD were scarcely described, and longitudinal evaluation of NMOSD lesions was only accessed in a few adult-onset cohorts. Methods: This study evaluated brain, spinal cord, and optic nerve MRI of sixteen pediatric-onset AQP4-IgG positive NMOSD through a qualitative evaluation of lesion evolution. Lesions were classified as symptomatic or asymptomatic in acute or chronic phase (> 30 days from last attack) MRI.Results: Seventy MRI scans and 54 subsequent exams were evaluated. Most NMOSD lesions (74.5%) reduced, remained stable, or developed atrophy/cavitation. New brain lesions or enlargement of existing brain lesions were found in two patients (12.5%) without any clinical symptom and in five patients (31.2%) in the course of an attack from other topography (optic neuritis or acute myelitis). One patient (6.3%) presented an asymptomatic spinal cord lesion irrespective of clinical manifestation. No asymptomatic lesion was described in optic nerve MRI. In acute phase exams, longitudinally extensive transverse myelitis (13/19 vs 8/24; p = 0.033), cervical myelitis (15/19 vs 10/24, p = 0.028), lumbar myelitis (5/19 vs 0/24; p = 0.012), and a higher number of segments [median 8 (range 4-17) vs 3.5 (range 1-14); p = 0.003] were affected.Conclusions: Asymptomatic brain and spinal cord lesions can occur in pediatric-onset NMOSD, especially in the course of acute optic neuritis or myelitis. More longitudinal studies are necessary to guide recommendations on neuroimaging frequency in pediatric patients with AQP4-IgG NMOSD.
  • article 0 Citação(ões) na Scopus
    A comparative study of visual outcome in patients with optic neuritis treated with five or seven days of intravenous corticosteroid treatment
    (2023) SILVA, Guilherme Diogo; TERRIM, Sara; FALCAO, Fernando Cavalcantide Sa e Benevides; FALCA, Maria Alice Pimentel; CHAVES, Cleuber Esteves; APOSTOLOS-PEREIRA, Samira; FORTINI, Ida; GONCALVES, Marcia Rubia Rodrigues; COMERLATTI, Luiz Roberto; CASTRO, Luiz Henrique Martins; CALLEGARO, Dagoberto; MONTEIRO, Mario Luiz Ribeiro
    Background: Optic neuritis (ON), a major cause of visual impairment in young adults, is generally associated with rapid visual recovery when treated with intravenous methylprednisolone treatment (IVMPT). However, the optimal duration of such treatment is unknown, ranging from three to seven days in clinical practice. We aimed to compare the visual recovery in patients treated with 5-day or 7-day duration IVMPT.Methods: We performed a retrospective cohort study of consecutive patients with ON in Sa similar to o Paulo, Brazil, from 2016 to 2021. We compared the proportion of participants with visual impairment in 5-day and 7-day treatment schedules at discharge, at 1 month and between 6 and 12 months after the diagnosis of ON. The findings were adjusted to age, severity of the visual impairment, co-intervention with plasma exchange, time from symptom onset to IVMPT and the etiology of the ON to mitigate indication bias.Results: We included 73 patients with ON treated with 5 or 7-day duration of 1 g/d intravenous methylprednisolone therapy. Visual impairment at 6-12 months in the 5-day or the 7-day treatment groups was similar (57% x 59%, p > 0.9, Odds Ratio 1.03 [95% CI 0.59-1.84]). The results were similar after adjusting for prognostic variables and when observed at different time points.Conclusion: Visual recovery is similar in patients treated with 5-day and 7-day duration treatments of 1 g/day intravenous methylprednisolone, suggesting a ceiling effect. Limiting the duration of the treatment can reduce hospital stay and costs, without interfering with clinical benefit.
  • article 4 Citação(ões) na Scopus
    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 Paula
    Purpose 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.
  • article 12 Citação(ões) na Scopus
    Drug-related demyelinating syndromes: understanding risk factors, pathophysiological mechanisms and magnetic resonance imaging findings
    (2021) RIMKUS, Carolina M.; SCHOEPS, Vinicius Andreoli; BOAVENTURA, Mateus; GODOY, Luis Filipe; APOSTOLOS-PEREIRA, Samira Luisa; CALICH, Ana Luisa; CALLEGARO, Dagoberto; LUCATO, Leandro Tavares; ROVIRA, Alex; SASTRE-GARRIGA, Jaume; LEITE, Claudia da Costa
    Some drugs and medications can precipitate immune system deregulations, which might be confused with recurrent demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMO), exacerbations of an existing disease, neoplastic lesions or other conditions. In this narrative review we describe some of the most relevant drugs and medications associated with iatrogenic demyelination. The anthelminthic agent levamisole is a frequent cocaine adulterant and can precipitate an exacerbated immune response attacking the central nervous system (CNS). High-efficacy multiple sclerosis (MS) drugs might induce a selective CNS immunosuppression, making it susceptible for opportunistic infections that course with demye-lination, such as progressive multifocal leukoencephalopathy. Sometimes, the interruption of a high-efficacy drug to treat MS can induce a rapid CNS reentry of lymphocytes, exacerbating demyelinating processes and triggering rebound syndromes. Furthermore, selective cytokines inhibition, such as anti-TNF alpha agents, might induce an imbalance between cell death and proliferation inducing a paradoxical increase of CNS tumor necrosis factor (TNF), affecting the activity of lymphocytes, microglia and macrophages, triggering aberrant inflammation and demyelination. Immune checkpoint inhibitors are a new class of antineoplastic drugs that enhance the immune response against tumor cells by an upregulation of T-cell activity. However, this hyperactivation of the immune system might be associated with induction of unwanted autoimmune responses. In this paper we review the risk factors, the possible pathological mechanisms and the magnetic resonance imaging (MRI) findings of these drug-related demyelinating syndromes.
  • article 103 Citação(ões) na Scopus
    Quantification of Retinal Neural Loss in Patients with Neuromyelitis Optica and Multiple Sclerosis with or without Optic Neuritis Using Fourier-Domain Optical Coherence Tomography
    (2012) MONTEIRO, Mario L. R.; FERNANDES, Danilo B.; APOSTOLOS-PEREIRA, Samira L.; CALLEGARO, Dagoberto
    PURPOSE. We compared retinal nerve fiber layer (RNFL) and macular thickness measurements in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) with or without a history of optic neuritis, and in controls using Fourier-domain (FD) optical coherence tomography (OCT). METHODS. Patients with MS (n = 60), NMO (n = 33), longitudinal extensive transverse myelitis (LETM, n = 28) and healthy controls (n = 41) underwent ophthalmic examination, including automated perimetry, and FD-OCT RNFL and macular thickness measurements. Five groups of eyes were compared: MS with or without previous optic neuritis, NMO, LETM, and controls. Correlation between OCT and visual field (VF) findings was investigated. RESULTS. With regard to most parameters, RNFL and macular thickness measurements were significantly smaller in eyes of each group of patients compared to controls. MS eyes with optic neuritis did not differ significantly from MS eyes without optic neuritis, but measurements were smaller in NMO eyes than in all other groups. RNFL (but not macular thickness) measurements were significantly smaller in LETM eyes than in controls. While OCT abnormalities were correlated significantly with VF loss in NMO/LETM and MS, the correlation was much stronger in the former. CONCLUSIONS. Although FD-OCT RNFL and macular thickness measurements can reveal subclinical or optic neuritis-related abnormalities in NMO-spectrum and MS patients, abnormalities are predominant in the macula of MS patients and in RFNL measurements in NMO patients. The correlation between OCT and VF abnormalities was stronger in NMO than in MS, suggesting the two conditions differ regarding structural and functional damage. (ClinicalTrials.gov number, NCT01024985.) Invest Ophthalmol Vis Sci. 2012;53:3959-3966) DOI:10.1167/iovs.11-9324
  • article 27 Citação(ões) na Scopus
    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 Costa
    Background: 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.
  • article 47 Citação(ões) na Scopus
    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 Kazutoshi
    Background: 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.
  • article 168 Citação(ões) na Scopus
    Myasthenia gravis and neuromyelitis optica spectrum disorder A multicenter study of 16 patients
    (2012) LEITE, M. I.; COUTINHO, E.; LANA-PEIXOTO, M.; APOSTOLOS, S.; WATERS, P.; SATO, D.; MELAMUD, L.; MARTA, M.; GRAHAM, A.; SPILLANE, J.; VILLA, A. M.; CALLEGARO, D.; SANTOS, E.; SILVA, A. Martins da; JARIUS, S.; HOWARD, R.; NAKASHIMA, I.; GIOVANNONI, G.; BUCKLEY, C.; HILTON-JONES, D.; VINCENT, A.; PALACE, J.
    Objective: To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG). Methods: The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively. Results: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. Conclusions: Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed.