Josiane Lopes

Oxidative stress in multiple sclerosis patients in clinical remission: Association with the expanded disability status scale

Increased levels of oxidative stress markers and/or decreased levels of antioxidant molecules have been described in patients with multiple sclerosis (MS). This imbalance has been implicated in demyelination and axonal damage. The aims of this study were to evaluate oxidative stress in MS patients and to verify its correlation with disability as assessed by the expanded disability status scale (EDSS). This case-controlled study included 91 patients with relapsing-remitting multiple sclerosis (RR-MS) and 196 healthy individuals matched by age, gender, ethnicity, smoking status, and body mass index. Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), sulfhydryl groups of proteins and serum uric acid levels. MS patients exhibited higher plasma levels of CL-LOOH (p<0.0001) and carbonyl protein (p=0.0081), and lower plasma levels of NOx (p<0.0001), TRAP (p=0.0088), and sulfhydryl groups (p=0.0003) compared to the control subjects. A multivariate analysis showed an association between oxidative markers and the presence of MS. Patients with an EDSS >3.5 showed higher CL-LOOH than control subjects (p=0.0093). A positive correlation was observed between CL-LOOH and EDSS (r=0.3244, p=0.0026) and between carbonyl protein and EDSS (r=0.3012, p=0.0041). These results demonstrate that oxidative stress plays an important role in the physiopathology of MS progression.

Long-term use of glatiramer acetate by 11 pregnant women with multiple sclerosis: a retrospective, multicentre case series.

AbstractBackground: Glatiramer acetate is a US FDA category B drug with regard to use by pregnant women with multiple sclerosis (MS). There are no data currently available for the continuous use of glatiramer acetate during pregnancy. Objective: To assess the risks and benefits of glatiramer acetate used throughout pregnancy among women with active MS. Design: Retrospective and multicentre case series. Settings: Outpatient services of academic and private institutions caring for patients with MS in Brazil. Patients: Eleven women with MS and their children were assessed. Intervention: Retrospective evaluation of women with MS who received glatiramer acetate continuously for at least 7 months during pregnancy. This evaluation was performed by the neurologist responsible for the patient. Children aged 1 year and over, born to mothers who received glatiramer acetate during pregnancy, were assessed using the Denver II developmental screening test. Main Outcome Measurements: Obstetric, neonatal and developmental outcomes. Results: No drug-related obstetric complications were observed. No specific drug-related malformations, neonatal complications or developmental abnormalities were observed in the children. Postnatal MS relapse rates remained significantly lower than antenatal rates in these patients. Conclusions: No deleterious effects from glatiramer acetate were observed in these pregnant women with MS or in their offspring. No increment in postnatal relapse rate was observed. However, the use of glatiramer acetate during pregnancy should be restricted to the most difficult cases, in which the benefits clearly outweigh the risks.

An assessment of the RIFLE criteria for acute renal failure following myeloablative autologous and allogeneic haematopoietic cell transplantation

An assessment of the RIFLE criteria for acute renal failure following myeloablative autologous and allogeneic haematopoietic cell transplantation

Disability in patients with multiple sclerosis: influence of insulin resistance, adiposity, and oxidative stress.

OBJECTIVE The aims of the present study were to report the prevalence of insulin resistance (IR) in patients with multiple sclerosis (MS); to verify differences in metabolic and inflammatory biomarkers, and oxidative stress in patients with MS with or without IR; and to assess if IR and adiposity are associated with disability in these patients. METHODS The study enrolled 110 patients with MS and 175 healthy individuals. Patients with MS were divided in those with IR (n = 44) and those without (n = 66). Metabolic and inflammatory markers, oxidative stress, and disability were evaluated by the Extended Disability Status Scale (EDSS). RESULTS IR prevalence was verified in 40% of the patients with MS and in 21.1% of the control group (odds ratio, 2.48; 95% confidence interval, 1.469-4.210; P = 0.0006). Patients with the disease and IR showed higher EDSS (P = 0.031), interleukin (IL)-6 (P = 0.028), IL-17 (P = 0.006), oxidative stress evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (P = 0.029), and advanced oxidation protein products (P = 0.025) than those patients without IR. The multivariate analysis showed that disability was associated with IR evaluated by homeostasis model assessment of insulin resistance (P = 0.030) and adiposity evaluated by waist circumference (P = 0.0179) and body mass index (P = 0.0033). CONCLUSION This is the first study to demonstrate an increase IR prevalence and the association between IR and adiposity with disability assessed by EDSS in patients with MS. IR seems to be associated with chronic inflammatory process and oxidative stress in patients with MS. More studies are warranted to elucidate the mechanisms by which IR and adiposity could contribute to the progression and disability in patients with MS.

HLA-DRB1* allele-associated genetic susceptibility and protection against multiple sclerosis in Brazilian patients.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system that causes neurological disorders in young adults. Previous studies in various populations highlighted an association between the HLA-DRB1*15 allele and MS. This study investigated the association between HLA-DRB1*15 and other HLA-DRB1 alleles and MS in a Brazilian Caucasian population sample from Londrina, Southern Brazil. HLA-DRB1 alleles were analyzed by polymerase chain reaction with specific sequence oligonucleotide primers in 119 MS patients and in 305 healthy blood donors as a control. Among the MS patients, 89 (75.0%) presented with relapsing remitting MS, 24 (20.0%) with secondary progressive MS and 6 (5.0%) with primary progressive MS. The frequency of the HLA-DRB1*15 allele observed in the MS Brazilian patients was similar to findings reported in previous studies carried out in populations worldwide. However, the results showed a higher frequency of the HLA-DRB1*15 allele in the MS patients compared to the controls, with a relative frequency of 0.1050 (10.50%) and 0.0443 (4.4%), respectively (OR=2.53; 95% CI 1.43-4.46; p=0.0009). A protector allele was also detected. The frequency of the HLA-DRB1*11 allele was reduced in the MS patients compared to the controls, with a relative frequency of 0.1345 (13.4%) and 0.1869 (18.7%), respectively (OR=0.67; 95% CI 0.44-1.03; p=0.0692). The results demonstrated that the HLA-DRB1*15 allele in heterozygosity is positively associated with MS (p=0.0079), and may be considered a genetic marker of susceptibility to the disease. A negative association between the HLA-DRB1*11 allele in homozygosity and MS was also verified (p=0.0418); this allele may be considered a genetic marker of resistance to MS in the Brazilian population.

Contemporary analysis of the influence of acute kidney injury (AKI) after myeloablative hematopoietic cell transplantation on long-term patient's survival.

Contemporary analysis of the influence of acute kidney injury (AKI) after myeloablative hematopoietic cell transplantation on long-term patients survival

Cytokine Profile in Patients with Progressive Multiple Sclerosis and Its Association with Disease Progression and Disability

Inflammation is the driving force for brain injury in patients with multiple sclerosis (MS). The objective of the present study is to delineate the serum cytokine profile in patients with progressive MS in a Southern Brazilian population compared with healthy controls and patients with relapsing-remitting MS (RRMS) and its associations with disease progression and disability. We included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-10, IL-4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay. IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in progressive MS than in controls. Increased IL-1β and IFN-γ and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients with progressive MS with disease progression presented higher TNF-α, IFN-γ, and IL-10 levels than those without disease progression. Patients with progressive MS with disease progression showed a higher frequency of positive gadolinium-enhanced lesions in MRI; higher TNF-α, IFN-γ, and IL-17 levels; and decreased IL-12 levels compared with RRMS patients with progression. There was a significant inverse correlation between IL-10 levels and EDSS score in patients with progressive MS. The results underscore the complex cytokine network imbalance exhibited by progressive MS patients and show the important involvement of TNF-α, IFN-γ, and IL-17 in the pathophysiology and progression of the disease. Moreover, serum IL-10 levels were inversely associated with disability in patients with progressive MS.

Restless legs syndrome and multiple sclerosis: a Brazilian multicenter study and meta-analysis of the literature

OBJECTIVE The increased prevalence of restless legs syndrome (RLS) in multiple sclerosis (MS) has recently been the subject of a few papers. The present study investigated the prevalence of RLS symptoms in MS patients and in controls in four Brazilian cities. Additionally, a systematic review and meta-analysis of the literature was carried out on the subject of RLS-MS. METHOD MS patients and controls were investigated regarding the presence of the four typical symptoms of RLS. A questionnaire assessing RLS severity was also used for patients and controls presenting the four RLS symptoms criteria. The systematic review and meta-analysis on the subject were carried out according to the strict international criteria. RESULTS In the present report, the RLS-MS association was confirmed as being more than fortuitous in Brazilian MS patients, in a multicenter case-control study. MS patients also presented RLS symptoms of greater severity than did the control population. A systematic review and meta-analysis of the literature showed that MS patients had a fourfold higher chance of presenting RLS than did the controls. CONCLUSION Although underlying mechanisms to explain the association RLS-MS are still a matter of discussion, there is a clear association of these two neurological conditions.

Multiple sclerosis starting before the age of 18 years: the Brazilian experience

Multiple sclerosis (MS) starting in childhood and adolescence poses a challenge for diagnosis and management of the disease. The aim of the present study was to assess the characteristics of early onset MS in Brazilian patients. Methods Retrospective data collection from specialized MS units. Results From 20 MS units in 11 Brazilian states, 117 cases of MS starting before the age of 18 years were collected. These patients had an average of 10 years of disease duration, still typically with low disability and one relapse every 2.5 years. The mean age for disease onset was 13.7 years. Conclusion The present study introduces a large series of Brazilian cases of pediatric MS. Although some patients presented a very severe form of MS, on the whole the group of patients with MS starting in childhood or adolescence presented a relatively mild form of this disease in Brazil.

Neurological complications following bariatric surgery

OBJECTIVE It was to report on Brazilian cases of neurological complications from bariatric surgery. The literature on the subject is scarce. METHOD Cases attended by neurologists in eight different Brazilian cities were collected and described in the present study. RESULTS Twenty-six cases were collected in this study. Axonal polyneuropathy was the most frequent neurological complication, but cases of central demyelination, Wernicke syndrome, optical neuritis, radiculits, meralgia paresthetica and compressive neuropathies were also identified. Twenty-one patients (80%) had partial or no recovery from the neurological signs and symptoms. CONCLUSION Bariatric surgery, a procedure that is continuously increasing in popularity, is not free of potential neurological complications that should be clearly presented to the individual undergoing this type of surgery. Although a clear cause-effect relation cannot be established for the present cases, the cumulative literature on the subject makes it important to warn the patient of the potential risks of this procedure.