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
44 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 44
- 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.
- 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 deBackground 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.
- 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.
- 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.
- 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.
- 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.