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
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- 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, KazuoTo 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.
- Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis(2022) SILVA, Guilherme Diogo; CASTRILLO, Bruno Batitucci; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, DagobertoOcrelizumab and siponimod are the two on-label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high-efficacy disease-modifying drugs (DMDs). Off-label prescription of other high-efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on-label and off-label high-efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High-efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta-analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on-label and off-label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off-label drugs (CI95% 0.51-2.16) versus ocrelizumab (reference) and off-label drugs (CI 95% 0.53-1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off-label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on-label DMDs in this network meta-analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS.
- MOG-IgG-Associated Optic Neuritis, Encephalitis, and Myelitis: Lessons Learned From Neuromyelitis Optica Spectrum Disorder(2018) PASSOS, Giordani Rodrigues dos; OLIVEIRA, Luana Michelli; COSTA, Bruna Klein da; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, Dagoberto; FUJIHARA, Kazuo; SATO, Douglas KazutoshiAntibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been found in some cases diagnosed as seronegative neuromyelitis optica spectrum disorder (NMOSD). MOG-IgG allowed the identification of a subgroup with a clinical course distinct from that of NMOSD patients who are seropositive for aquaporin-4-IgG antibodies. MOG-IgG is associated with a wider clinical phenotype, not limited to NMOSD, with the majority of cases presenting with optic neuritis (ON), encephalitis with brain demyelinating lesions, and/or myelitis. Therefore, we propose the term MOG-IgG-associated Optic Neuritis, Encephalitis, and Myelitis (MONEM). Depending on the clinical characteristics, these patients may currently be diagnosed with NMOSD, acute disseminated encephalomyelitis, pediatric multiple sclerosis, transverse myelitis, or ON. With specific cell-based assays, MOG-IgG is emerging as a potential biomarker of inflammatory disorders of the central nervous system. We review the growing body of evidence on MONEM, focusing on its clinical aspects.
- 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 KazutoshiBackground 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.
- 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 CostaSome 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.
- Therapeutic plasma exchange for neuromyelitis optica attacks: Evidence and challenges from a real-world cohort from Brazil(2024) ALMEIDA, Guilherme Mello Ramos de; ARAUJO, Roger Santana de; CASTRILLO, Bruno Batitucci; SILVA, Guilherme Diogo; FORTINI, Ida; GONCALVES, Marcia Rubia Rodrigues; CASTRO, Luiz Henrique Martins; TATSUI, Nelson Hidekazu; ADONI, Tarso; SATO, Douglas Kazutoshi; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, DagobertoTherapeutic plasma exchange (TPE) can improve disability recovery after neuromyelitis optica spectrum disease (NMOSD) attacks, but its effectiveness and safety in Latin-American patients with access barriers and diverse ethnicity is underexplored. We carried out a retrospective cohort study with NMOSD patients that underwent TPE. 84 NMOSD attacks in 68 patients were evaluated. Despite a median 25-day delay from symptom onset to TPE, 65,5% of patients showed significant improvement. Adverse events occurred in 39% of patients, usually transitory and with no fatalities.
- 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.
- Anti-MOG (Myelin Oligodendrocyte Glycoprotein)-Positive Severe Optic Neuritis with Optic Disc Ischaemia and Macular Star(2015) MOURA, Frederico Castelo; SATO, Douglas Kazutoshi; RIMKUS, Carolina Medeiros; APOSTOLOS-PEREIRA, Samira Luisa; OLIVEIRA, Luana Michelli de; LEITE, Claudia Costa; FUJIHARA, Kazuo; MONTEIRO, Mario Luiz Ribeiro; CALLEGARO, DagobertoA 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG).
- Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders(2014) SATO, Douglas Kazutoshi; CALLEGARO, Dagoberto; LANA-PEIXOTO, Marco Aurelio; WATERS, Patrick J.; JORGE, Frederico M. de Haidar; TAKAHASHI, Toshiyuki; NAKASHIMA, Ichiro; APOSTOLOS-PEREIRA, Samira Luisa; TALIM, Natalia; SIMM, Renata Faria; LINO, Angelina Maria Martins; MISU, Tatsuro; LEITE, Maria Isabel; AOKI, Masashi; FUJIHARA, KazuoObjective:To evaluate clinical features among patients with neuromyelitis optica spectrum disorders (NMOSD) who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) antibodies, or seronegativity for both antibodies.Methods:Sera from patients diagnosed with NMOSD in 1 of 3 centers (2 sites in Brazil and 1 site in Japan) were tested for MOG and AQP4 antibodies using cell-based assays with live transfected cells.Results:Among the 215 patients with NMOSD, 7.4% (16/215) were positive for MOG antibodies and 64.7% (139/215) were positive for AQP4 antibodies. No patients were positive for both antibodies. Patients with MOG antibodies represented 21.1% (16/76) of the patients negative for AQP4 antibodies. Compared with patients with AQP4 antibodies or patients who were seronegative, patients with MOG antibodies were more frequently male, had a more restricted phenotype (optic nerve more than spinal cord), more frequently had bilateral simultaneous optic neuritis, more often had a single attack, had spinal cord lesions distributed in the lower portion of the spinal cord, and usually demonstrated better functional recovery after an attack.Conclusions:Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies.
- Clinical Features of COVID-19 on Patients With Neuromyelitis Optica Spectrum Disorders(2021) APOSTOLOS-PEREIRA, Samira Luisa; FERREIRA, Lis Campos; BOAVENTURA, Mateus; SOUSA, Nise Alessandra de Carvalho; MARTINS, Gabriela Joca; D'ALMEIDA, Jose Arthur; PITOMBEIRA, Milena; MENDES, Lucas Silvestre; FUKUDA, Thiago; CABECA, Hideraldo Luiz Souza; ROCHA, Luciano Chaves; OLIVEIRA, Bianca Santos de; STELLA, Carla Renata Vieira; OLIVEIRA, Enedina Maria Lobato de; AMORIM, Leizian de Souza; CASTRO, Andrea Ferrari de; GOMES NETO, Antonio Pereira; SILVA, Guilherme Diogo; BUENO, Lucas; MACHADO, Maria de Morais; DIAS-CARNEIRO, Rafael Castello; DIAS, Ronaldo Maciel; MOREIRA, Alvaro Porto; PICCOLO, Ana; GRZESIUK, Anderson Kuntz; MUNIZ, Andre; DISSEROL, Caio Diniz; VASCONCELOS, Claudia Ferreira; KAIMEN-MACIEL, Damacio; DINIZ, Denise Sisterolli; COMINI-FROTA, Elizabeth; ROCHA, Fernando Coronetti; SANTOS, Gutemberg Augusto Cruz dos; FRAGOSO, Yara Dadalti; OLIVAL, Guilherme Sciascia do; RUOCCO, Heloisa Helena; SIQUEIRA, Heloise Helena; SATO, Henry Koity; FIGUEIREDO JR., Jose Alexandre; CALIA, Leandro Cortoni; DOURADO JR., Mario Emilio Teixeira; SCOLARI, Leticia; SOARES NETO, Herval Ribeiro; MELGES, Luiz; GONCALVES, Marcus Vinicius Magno; PIMENTEL, Maria Lucia Vellutini; RIBEIRO, Marlise de Castro; ARAMBULA, Omar Gurrola; GAMA, Paulo Diniz da; MENON, Renata Leite; THOMAZ, Rodrigo Barbosa; MORALES, Rogerio de Rizo; SOBREIRA, Silvana; MACHADO, Suzana Nunes; RIBEIRO, Taysa Gonsalves Jube; PEREIRA, Valeria Coelho Santa Rita; COSTA, Vanessa Maia; NOBREGA JUNIOR, Adaucto Wanderley da; ALVES-LEON, Soniza Vieira; PERIN, Marilia Mamprim de Morais; DONADI, Eduardo; ADONI, Tarso; GOMES, Sidney; FERREIRA, Maria Brito; CALLEGARO, Dagoberto; MENDES, Maria Fernanda; BRUM, Doralina; GLEHN, Felipe vonBackground and Objectives To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD). Methods The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described. Results Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection. Discussion Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations.