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
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- 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.
- 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.
- 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.
- 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 CostaBackground: 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.
- 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.
- Reduced quality of life in a pediatric-onset Neuromyelitis optica spectrum disorders cohort(2021) PAOLILO, Renata Barbosa; PAZ, Jose Albino da; APOSTOLOS-PEREIRA, Samira Luisa; RIMKUS, Carolina de Medeiros; CALLEGARO, Dagoberto; SATO, Douglas KazutoshiBackground: Neuromyelitis optica spectrum disorders (NMOSD) is a severe condition associated with high disability and low quality of life (QoL) in adults. Since this evaluation had been rarely perfomed in children, this study aimed to describe QoL in pediatric-onset NMOSD with positive aquaporin4 antibody (AQP4-IgG) patients. Methods: This was a cross-section evaluation of patients and parents' proxy QoL from individuals enrolled in a longitudinal cohort of AQP4-IgG positive NMOSD with onset <= 18 years of age. Results: Eighteen patients were included, sixteen girls. The mean (SD) age at disease onset was 11.5 (3.6) years. Eleven of patients experienced disability during a mean (SD) of 8.3 (5.3) years of follow-up. NMOSD had impact in QoL in 10 patients, being associated with higher EDSS and poor academic performance at last follow-up. Results from the PedsQL inventory for 13 patients and 10 parents disclosed low QoL specially in emotional functioning. Conclusion: This study indicates impaired quality of life, high disability and high impact of the disease in daily life of adolescents and young adults with pediatric onset NMOSD.
- 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.
- Vitamin D3 as an add-on treatment for multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials(2024) MAHLER, Joao Vitor; SOLTI, Marina; APOSTOLS-PEREIRA, Samira Luisa; ADONI, Tarso; SILVA, Guilherme Diogo; CALLEGARO, DagobertoBackground: Vitamin D deficiency has been linked to a higher risk of multiple sclerosis (MS) and disease progression. However, the efficacy of vitamin D3 as an adjuvant therapy for MS remains a controversial topic. Objective: To perform a systematic review and meta-analysis of randomized controlled trials to assess the impact of adjunct high-dose vitamin D3 on clinical and radiological outcomes. Methods: PubMed, Embase, and Cochrane Library were searched for trials published until December 18th, 2022. Authors independently selected randomized controlled trials involving patients with MS, with an intervention group receiving high dose (>= 1000 IU/day) cholecalciferol and reporting clinical or radiological outcomes. Authors independently extracted data and assessed the risk of bias using a standardized, pilot-tested form. The meta-analysis was conducted using RStudio for EDSS at the last follow-up, ARR, and new T2 lesion count. Results: We included 9 studies with 867 participants. No significant reduction of EDSS (MD = 0.02, CI 95 % [-0.37; 0.41], p = 0.91), ARR (MD -0.03, CI 95 % [-0.08; 0.02], p = 0.26), or new T2 lesions (MD -0.59, CI 95 % [-1.24;0.07], p = 0.08) was observed at 6-24 months. We found no evidence of publication bias. Conclusion: The findings of this meta-analysis strengthen current evidence that vitamin D3 supplementation has no significant impact on clinical outcomes in patients with MS. However, the non-significant reduction of new T2 lesions could precede long-term clinical benefits and should be validated in additional studies.