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
15 resultados
Resultados de Busca
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- 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.
- Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach(2022) GOMES, Ana Beatriz Ayroza Galvao Ribeiro; FEO, Lucas Bueno; SILVA, Guilherme Diogo; DISSEROL, Caio Cesar Diniz; PAOLILO, Renata Barbosa; LARA, Amanda Nazareth; TONACIO, Adriana Coracini; MENDES, Maria Fernanda; PEREIRA, Samira Luisa Apostolos; CALLEGARO, DagobertoBackground Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease. Objective To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients. Methods Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario. Conclusion We propose a vaccination schedule, infectious screening routine, and prophylactic measures based on the current scientific evidence. Awareness of emergent tropical diseases is necessary due to evidence of demyelinating events and possible parainfectious cases of MS and NMOSD.
- 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 RibeiroBackground: 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.
- 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.
- Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system(2021) BECKER, Jefferson; FERREIRA, Lis Campos; DAMASCENO, Alfredo; BICHUETTI, Denis Bernardi; CHRISTO, Paulo Pereira; CALLEGARO, Dagoberto; PEIXOTO, Marco Aurelio Lana; SOUSA, Nise Alessandra de Carvalho; ALMEIDA, Sergio Monteiro de; ADONI, Tarso; SANTIAGO-AMARAL, Juliana; JUNQUEIRA, Thiago; PEREIRA, Samira Luisa Apostolos; GOMES, Ana Beatriz Ayroza Galvao Ribeiro; PITOMBEIRA, Milena; PAOLILO, Renata Barbosa; GRZESIUK, Anderson Kuntz; PICCOLO, Ana Claudia; ALMEIDA, Jose Arthur Costa D.; GOMES NETO, Antonio Pereira; OLIVEIRA, Augusto Cesar Penalva de; OLIVEIRA, Bianca Santos de; TAUIL, Carlos Bernardo; VASCONCELOS, Claudia Ferreira; KAIMEN-MACIEL, Damacio; VARELA, Daniel; DINIZ, Denise Sisterolli; OLIVEIRA, Enedina Maria Lobato De; MALFETANO, Fabiola Rachid; BORGES, Fernando Elias; FIGUEIRA, Fernando Faria Andrade; GONDIM, Francisco de Assis Aquino; PASSOS, Giordani Rodrigues dos; SILVA, Guilherme Diogo; OLIVAL, Guilherme Sciascia Do; SANTOS, Gutemberg Augusto Cruz dos; RUOCCO, Heloisa Helena; SATO, Henry Koiti; SOARES NETO, Herval Ribeiro; CALIA, Leandro Cortoni; GONCALVES, Marcus Vinicius Magno; VECINO, Maria Cecilia Aragon De; PIMENTEL, Maria Lucia Vellutini; RIBEIRO, Marlise de Castro; BOAVENTURA, Mateus; PAROLIN, Monica Koncke Fiuza; MELO, Renata Brant de Souza; LAZARO, Robson; THOMAZ, Rodrigo Barbosa; KLEINPAUL, Rodrigo; DIAS, Ronaldo Maciel; GOMES, Sidney; LUCATTO, Simone Abrante; ALVES-LEON, Soniza Vieira; FUKUDA, Thiago; RIBEIRO, Taysa Alexandrino Gonsalves Jube; WINCKLER, Thereza Cristina D'avila; FRAGOSO, Yara Dadalti; NASCIMENTO, Osvaldo Jose Moreira do; FERREIRA, Maria Lucia Brito; MENDES, Maria Fernanda; BRUM, Doralina Guimaraes; GLEHN, Felipe VonThe Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases.The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.
- 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.
- Paracentral Acute Middle Maculopathy Associated with Severe Anti-Mog (Myelin Oligodendrocyte Glycoprotein)-Positive Optic Neuritis(2023) FERNANDES, Rodrigo Dahia; ANDRADE, Thais de Souza; PRETI, Rony C. C.; ZACHARIAS, Leandro C. C.; SILVA, Guilherme Diogo; LUCATO, Leandro Tavares; APOSTOLOS-PEREIRA, Samira L. L.; CALLEGARO, Dagoberto; MONTEIRO, Mario Luiz R.Retinal complications in patients with inflammatory optic neuritis (ON) are generally related to post-infectious neuroretinitis and are considered uncommon in autoimmune/demyelinating ON, whether isolated or caused by multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). More recently, however, cases with retinal complications have been reported in subjects positive for myelin oligodendrocyte glycoprotein (MOG) antibodies. We report a 53-year-old woman presenting with severe bilateral ON associated with a focal area of paracentral acute middle maculopathy (PAMM) in one eye. Visual loss recovered remarkably after high-dose intravenous corticosteroid treatment and plasmapheresis, but the PAMM lesion remained visible on both optical coherence tomography and angiography as an ischaemic lesion affecting the middle layers of the retina. The report emphasises the possible occurrence of retinal vascular complications in MOG-related optic neuritis, an important addition to the diagnosis of, and possible differentiation from, MS-related or NMOSD-related ON.
- 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.
- Estimated prevalence of AQP4 positive neuromyelitis optica spectrum disorder and MOG antibody associated disease in Sa tilde o Paulo, Brazil(2023) SILVA, Guilherme Diogo; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, DagobertoBackground: Numerous studies addressed the prevalence of multiple sclerosis, but prevalence studies of NMOSD and, particularly, MOGAD are scarce. We aimed to estimate the prevalence of NMOSD and MOGAD in the city of Sa tilde o Paulo, based on the known prevalence of MS.Methods: In this observational study, we determined the total number of patients with central nervous system demyelinating disease on regular follow-up in a university referral center in Sa tilde o Paulo, from May 2019 to May 2021 according to the diagnosis of multiple sclerosis (MS), NMOSD and MOGAD using the current diagnostic criteria for these diseases. We used the MS: NMOSD and MS: MOGAD ratios to estimate the ratio of these diseases in Sa tilde o Paulo, Brazil.Results: We identified 968 patients with MS, 133 patients with AQP4 positive NMOSD, and 28 patients with MOGAD. We found the MS: NMOSD ratio of 7,28 and the MS: MOGAD ratio of 34,57. We estimated a prevalence of 2,1 per 100,000 inhabitants for NMOSD and of 0,4 per 100,000 inhabitants for MOGAD.Conclusion: The prevalence of NMOSD is high in Sa tilde o Paulo, but the prevalence of MOGAD is low when compared with the prevalence found in most of the studies reported to date.
- Cost, efficacy, and safety comparison between early intensive and escalating strategies for multiple sclerosis: A systematic review and meta-analysis(2023) PIPEK, Leonardo Zumerkorn; MAHLER, Joao Vitor; NASCIMENTO, Rafaela Farias Vidigal; APOSTOLOS-PEREIRA, Samira Luisa; SILVA, Guilherme Diogo; CALLEGARO, DagobertoBackground: The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low-to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies.Methods: We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost.Results: Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model.Discussion: EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.