Papers by Carlos Otávio Brandão
Frontiers in Cellular Neuroscience, 2021
BackgroundNeurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have... more BackgroundNeurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have been correlated with the reduction of axonal damage in multiple sclerosis (MS) patients treated with Natalizumab (NTZ). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients.ObjectiveTo evaluate CSF NfL, serum levels of soluble-HLA-G (sHLA-G), and eventual tolerogenic behavior of plasmacytoid dendritic cells (pDCs) in MS patients during NTZ treatment.MethodsCSF NfL and serum sHLA-G levels were measured using an ELISA assay, while pDCs (BDCA-2+) were accessed through flow cytometry analyses.ResultsCSF levels of NfL were significantly reduced during NTZ treatment, while the serum levels of sHLA-G were increased. Moreover, NTZ treatment enhanced tolerogenic (HLA-G+, CD274+, and HLA-DR+) molecules and migratory (CCR7+) functions of pDCs in the peripheral blood.ConclusionThese findings suggest that NTZ stimulates the production of molecules with immunor...
International Immunopharmacology, 2009
Immunotherapy with Interferon-beta (IFNβ) results in remarkably beneficial effects in patients wi... more Immunotherapy with Interferon-beta (IFNβ) results in remarkably beneficial effects in patients with relapsing-remitting multiple sclerosis (MS), although the mechanisms by which it exerts these beneficial effects remain poorly understood. An investigation was made of the effects of IFNβ on pro-inflammatory and anti-inflammatory cytokine production in peripheral blood cells in MS patients, both untreated and those undergoing immunotherapy, as well as in healthy controls.Results show a significant increase in the production of pro-inflammatory cytokines such as TNFα, IFNγ and IL-12 in the plasma and in the supernatant of leukocyte cultures from MS patients with the untreated disease; IFNβ administration significantly reduced the levels of TNFα and IFNγ, with no changes in the level of IL-12. The Interferon-beta therapy also led to a significant increase in the production of IL-10, as well as a slight increase in that of TGFβ.The reduction in pro-inflammatory cytokine production in the...
Journal of Neuroimmunology, 2016
Given the low detection rates of CSF IgG-Oligoclonal bands (IgG-OCB) in non-European Multiple Scl... more Given the low detection rates of CSF IgG-Oligoclonal bands (IgG-OCB) in non-European Multiple Sclerosis (MS) patients and higher specificity of the MRZH-reaction, we evaluated whether associating MRZH-reaction to CSF IgG-OCB detection improved investigation of suspected MS. Paired CSF and sera were analyzed for IgG-OCB and polyspecific viral antibodies. IgG-OCB were detected in 72% of MS patients and an MRZH-reaction in 67%. Combining IgG-OCB and MRZH raised detection of IgG abnormalities to 97% of studied MS patients. Detection of IgG-OCB and/or ≥2 MRZH antibodies showed sensitivity of 88% and specificity of 92% for MS, versus 72% and 96% for IgG-OCB alone.
Neuromyelitis optica (NMO) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP... more Neuromyelitis optica (NMO) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are inflammatory diseases of the central nervous system. NMO is a syndrome of autoimmune etiology still not well defined and HAM/TSP is considered an immune-mediated disease associated with the infection of the HTLV-1 retrovirus, evolving with different clinical presentations. Recently, some acute cases of transverse myelitis and/or optic neuritis during the course of HAM/TSP were described, with a clinical evolution similar to NMO and were called acute variant of HAM/TSP. These reports raised the possibility that HTLV-1 is related to NMO attacks due to the fact that autoimmune diseases are frequently triggered by viral infections in genetically susceptible individuals and that both diseases present high prevalences, coincidently, in certain areas of the world. The objective of the present study is to review acute cases of HAM/ TSP and discuss clinical, pathological and laboratory feat...
O líquor (Líquido Cefalorraquiano- LCR) é um fluído oligocelular, límpido e incolor que preenche ... more O líquor (Líquido Cefalorraquiano- LCR) é um fluído oligocelular, límpido e incolor que preenche os ventrículos cerebrais e o espaço subaracnóideo, circundando o encéfalo e a medula espinhal. Devido à proximidade do sistema nervoso, o estudo liquórico reflete o processo patológico que ocorre em diversos distúrbios neurológicos. O exame consiste principalmente na observação da composição físico-química, citológica, microbiológica e imunológica do LCR. As modificações detectadas na sua composição, fluxo e pressão auxiliam no diagnóstico e tratamento das patologias do sistema nervoso. A via de acesso ao LCR preconizada pela Academia Brasileira de Neurologia é a punção lombar (PL), que foi descrita por Quincke, em 1891. Atualmente, a PL é considerada um ato médico de rotina para anestesia, diagnóstico, pesquisa ou tratamento de doenças que acometem o sistema nervoso central (SNC) e raízes nervosas. A compreensão dos aspectos anatômicos é fundamental para o sucesso e a segurança do proce...
PLoS ONE, 2012
Introduction: The seroprevalence of human T-cell leukemia virus type 1 (HTLV-1) is very high amon... more Introduction: The seroprevalence of human T-cell leukemia virus type 1 (HTLV-1) is very high among Brazilians (,1:200). HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the most common neurological complication of HTLV-1 infection. HAM/TSP can present with an acute/subacute form of longitudinally extensive myelitis, which can be confused with lesions seen in aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorders (NMOSD) on MRI. Moreover, clinical attacks in patients with NMOSD have been shown to be preceded by viral infections in around 30% of cases.
Multiple Sclerosis Journal, 2011
Multiple Sclerosis Journal, 2012
Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abn... more Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known.
Multiple Sclerosis Journal, 2014
Background: Although aquaporin-4 (AQP4) is widely expressed in the human brain cortex, lesions ar... more Background: Although aquaporin-4 (AQP4) is widely expressed in the human brain cortex, lesions are rare in neuromyelitis optica (NMO) spectrum disorders (NMOSD). Recently, however, several studies have demonstrated occult structural brain atrophy in NMO. Objective: This study aims to investigate magnetic resonance imaging (MRI) patterns of gray matter (GM) and white matter (WM) abnormalities in patients with NMOSD and to assess the visual pathway integrity during disease duration correlation of the retinal nerve fiber layer (RNFL) and pericalcarine cortex thickness. Methods: Twenty-one patients with NMOSD and 34 matched healthy controls underwent both high-field MRI (3T) high-resolution T1-weighted and diffusion-tensor MRI. Voxel-based morphometry, cortical analyses (Freesurfer) and diffusion-tensor imaging (DTI) analyses (TBSS-FSL) were used to investigate brain abnormalities. In addition, RNFL measurement by optic-coherence tomography (OCT) was performed. Results: We demonstrate that NMOSD is associated with GM and WM atrophy, encompassing more frequently the motor, sensory and visual pathways, and that the extent of GM atrophy correlates with disease duration. Furthermore, we demonstrate for the first time a correlation between RNFL and pericalcarine cortical thickness, with cortical atrophy evolving over the course of disease. Conclusions: Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved.
Journal of the Neurological Sciences, 2013
Background: Daily practice is still faced with uncertainty in predicting the long-term disability... more Background: Daily practice is still faced with uncertainty in predicting the long-term disability of multiple sclerosis (MS). Most information comes from northern hemisphere cohorts, but in South America this information is scarce, and race, genetic and environmental factors could play an important role in the heterogeneity observed in disease outcomes. Methods: We evaluated 197 patients attending our MS Center gathering clinical and demographic information. Outcome measures analyzed were time from first clinical symptom to EDSS of 6, 7 and 8. For survival analysis we employed Cox regression models and the Kaplan-Meier method. Results: Time to EDSS 6 was 25.83 years (95% CI 15.36-36.31), and 36.25 years (95% CI 20.72-51.78) for EDSS 7. Male sex was associated with a 4.63 and 4.69 fold increased risk to EDSS 6 and 7, respectively (p b 0.001 and p = 0.006). Motor and brainstem symptoms at onset were also associated with an 8.1 and 13.1 fold increased risk to EDSS 6, respectively (p = 0.04 and p = 0.01). The number of relapses in five and ten years of disease onset was associated with a slightly increased risk to EDSS 8 (1.28 and 1.19, respectively; p = 0.032 and p = 0.015). Conclusions: Male patients presenting with frequent relapses, especially those with motor and brainstem involvement, deserve close observation and should be cautiously monitored to early signs of treatment failure.
BMC Complementary and Alternative Medicine, 2012
QOL as such is ignored. The regular use of self-evaluation scales such as the FAMS should help id... more QOL as such is ignored. The regular use of self-evaluation scales such as the FAMS should help identify problems which could be relieved, as well as helping evaluate the efficacy of traditional treatments, since such self-evaluations often reveal more rapid responses to treatment than do the more objective evaluations of trained professionals.
Multiple sclerosis is a chronic, inflammatory, immune-mediated disease of the central nervous sys... more Multiple sclerosis is a chronic, inflammatory, immune-mediated disease of the central nervous system. Current evidence indicates that a complex genetic trait associated with environmental factors probably triggers MS. The hypothesis is that the inflammatory response starts when CNS protein-specific CD4+ T cells become activated in the periphery, cross the blood/brain barrier, and induce CNS autoimmunity. A disturbed balance between cells that induce or cause demyelination and regulatory T cells capable of suppressing these auto-reactive T cells underlie MS pathogenesis. Inflammation and oxidative stress are major causes of tissue damage in the CNS. Diagnostic criteria include paraclinical laboratory assessments emphasizing the principle of lesions disseminated in time and space. Cerebrospinal fluid analysis remains mandatory in order to support the diagnosis and differentiate MS from other diseases. Disease modifying therapies (DMT) are available for MS patients like recombinant Int...
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Papers by Carlos Otávio Brandão