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
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- 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.
- 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.
- 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).
- Pathologic yawning in neuromyelitis optica spectrum disorders(2014) LANA-PEIXOTO, Marco A.; CALLEGARO, Dagoberto; TALIM, Natlia; TALIM, Livia E.; PEREIRA, Samira A.; CAMPOS, Gilberto BelisarioIntroduction: Brainstem, hypothalamic and cerebral symptoms may occur in neuromyelitis optica spectrum disorders (NMOSD). However, pathologic yawning has not been previously described in NMOSD patients. Patients and methods: Nine AQP4-IgG seropositive NMOSD patients experienced excessive yawning not related to sleep deprivation or fatigue. Results: Patients were female, aged 19-57 years (median, 39 years) at disease onset. Excessive yawning spells were the presenting symptom of the disease in five patients, lasted 2-16 weeks, and usually occurred in association with nausea, vomiting and hiccups. Brain MRI was abnormal in all patients and most frequently showed brainstem and hypothalamic lesions. Conclusion: Pathologic yawning may be a neglected although not a rare symptom in NMOSD.
- 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.
- Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination(2023) GOMES, Ana Beatriz Ayroza Galvao Ribeiro; KULSVEHAGEN, Laila; LIPPS, Patrick; CAGOL, Alessandro; CERDA-FUERTES, Nuria; NEZIRAJ, Tradite; FLAMMER, Julia; LERNER, Jasmine; LECOURT, Anne-Catherine; SIEBENBORN, Nina De Oliveira S.; CORTESE, Rosa; SCHAEDELIN, Sabine; SCHOEPS, Vinicius Andreoli; MATOS, Aline de Moura Brasil; MENDES, Natalia Trombini; PEREIRA, Clarissa dos Reis; MONTEIRO, Mario Luiz Ribeiro; APOSTOLOS-PEREIRA, Samira Luisa dos; SCHINDLER, Patrick; CHIEN, Claudia; SCHWAKE, Carolin; SCHNEIDER, Ruth; PAKEERATHAN, Thivya; AKTAS, Orhan; FISCHER, Urs; MEHLING, Matthias; DERFUSS, Tobias; KAPPOS, Ludwig; AYZENBERG, Ilya; RINGELSTEIN, Marius; PAUL, Friedemann; CALLEGARO, Dagoberto; KUHLE, Jens; PAPADOPOULOU, Athina; GRANZIERA, Cristina; PROBSTEL, Anne-KatrinIMPORTANCE Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination. OBJECTIVE To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls. DESIGN, SETTING, AND PARTICIPANTS This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022. MAIN OUTCOMES AND MEASURES Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG. RESULTS After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P =.048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P =.02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P <.001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]). CONCLUSION AND RELEVANCE In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination.
- 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.