Search

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Neuromyelitis optica (NMO) is associated with antibodies that target aquaporin-4 (AQP4), the presence of other autoimmune disorders, and multiple other autoantibodies. The aim of this research was to investigate the frequency of autoimmune diseases and the seropositivity for autoantibodies in patients with NMO from a southern Brazilian population. Materials and Methods: Twenty-two patients with NMO diagnosed according to the 2006 revised diagnostic criteria were included. Demographic and clinical data were obtained using a standard questionnaire and from medical records. Disability was evaluated using the Expanded Disability Status Scale (EDSS). All patients were treated with prednisone in combination with other immunosuppressive drugs. The patients were divided in two groups: 13 patients treated with 10 mg/day of prednisone (group 1), and 9 patients treated with >10 mg/day of prednisone (group 2). The results of the autoantibodies detected from peripheral blood samples of the NMO patients evaluated were anti-AQP4, thyroid-stimulating hormone (FSH) receptor antibodies (TRAb), antinuclear antibodies (ANA), antithyroid peroxidase antibodies (anti-TPO), antithyroglobulin antibodies (anti-Tg), and antibodies to double stranded DNA (anti-dsDNA). Results: NMO patients did not differ in age, sex, ethnicity, body mass index and corticosteroids therapy (p>0.05). The median age of disease onset and median disease duration were higher among group 1 than group 2 (48.5 years vs. 37 years; p=0.0482; 7 years vs. 2 years, p=0.0240, respectively). No difference was observed in the EDSS of patients (p>0.05). The seropositivity for anti-AQP4 was 69.2% in group 1 and 33.3% in group 2. Although the patients presented other autoimmune conditions, differences were not found in the serum levels of anti-AQP4, TRAb, ANA, anti-TPO, and anti-Tg antibodies (p>0.05). All tested negative for anti-dsDNA antibodies. Discussion and Conclusion: The results underscore the fact that NMO patients present controversial clinical and laboratory characteristics. [ABSTRACT FROM AUTHOR]

Introduction: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system. Insulin resistance (IR) is associated with neurological disorders and seems to be associated with a chronic inflammatory process and disability. This research aimed to evaluate IR in NMO patients and its correlation with disability. Materials and Methods: Demographic and clinical data were obtained from 22 NMO patients using a standard questionnaire and medical records. Disability was evaluated using the Expanded Disability Status Scale (EDSS). Glucose levels were obtained using a biochemical autoanalyzer; insulin was evaluated by a chemiluminescent microparticle immunoassay; and the homeostasis model assessment (HOMA) was used to measure IR, calculated according to the formula: fasting insulin (µU/mL) x fasting glucose (nmol/L)/22.5. IR was considered when the subject exhibited a HOMA index ≥2.114. Results: Twenty-one patients (95.5%) were female; 6 (27.3%) were Caucasian and 13 (59.1%) were Mulatto. The median age was 44.5 years, median age at disease onset was 36 years, and median disease duration was 6 years. Twenty-one (95.5%) patients presented a relapsing course and 1 (4.5%) a mono-phasic course. Although only one patient presented a monophasic course, 3 (13.6%) patients presented simultaneous myelitis and optic neuritis as initial events. All patients were treated with prednisone in combination with other immunosuppressive drugs. IR was observed in 11 (50%) patients. NMO patients presented a positive correlation between EDSS and insulin (r= 0.5617, p= 0.0100), and a positive correlation between EDSS and HOMA-IR (r=0.6016, p=0.0083). The use of corticosteroids did not differ between the groups with and without IR (p=0.3967). Discussion and Conclusion: The results suggest that IR might be associated with increased disability in NMO patients. These data underscore the importance of monitoring the metabolic profile of NMO patients in order to prevent and/or treat further cardiovascular comorbidities that may be related to disease progression. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system in which cytokines are key factors in the regulation of inflammatory responses. The aim of this study was to evaluate the role of interferon beta (IFN-β) and glatiramer acetate (GA) on cytokine levels in MS patients. Materials and Methods: A total of 160 MS patients were recruited and divided according to MS therapy: no treatment (n=25), treated with IFN-β (n=112), and treated with GA (n=23). Demographic and clinical characteristics were obtained using a standard questionnaire and medical records. Disability was evaluated using the Expanded Disability Status Scale (EDSS). Serum cytokines were measured using sandwich enzyme-linked immunosorbent assay. Results: Patients under IFN-p therapy presented a higher age than those under GA (p=0.0042). No difference was found between the groups for gender, ethnicity, and body mass index (p=0.7108, p=0.1284, and p=0.2461, respectively). No difference was also found in EDSS and disease progression between the groups (p=0.1415 and p=0.9455, respectively). No difference was obtained in IL-1, IL-6, IL-12, IFN-γ, IL-17, and IL-10 between the groups (p=0.9864, 0=0.2753, p=0.1585, p=0.2300, p=0.4960, and p=0.130; respectively). However, MS patients treated with IFN-β and GA presented lower levels of TNF-α than those with no therapy (p=0.0044), and those treated with IFN-β exhibited better effects in the increased levels of IL-4 than those treated with GA. In addition, IFN-β and GA were equally associated with increased levels of IL-4 when compared to those patients without treatment (p=0.0100). In patients treated with IFN-P therapy, the Thl/Th2 balance shifted toward a Th2 cytokine profile (p=0.0155). Discussion and Conclusion: The results of the present study showed that both IFN-β and GA therapies are associated with down-regulation of the inflammatory cytokine TNF-α and increased anti-inflammatory Il-4 cytokines, limiting the disability and disease progression of the MS patients. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown that the pyramidal functional system is directly correlated with disability in patients with Multiple Sclerosis (MS). Moreover, cytokines have been related to disability, exacerbations and MS progression. The aim of this study was to evaluate the association between inflammatory cytokines and anti-inflammatory cytokines with the pyramidal functions of MS patients. Materials and Methods: Demographic and clinical data were obtained from 117 MS patients. Disability was evaluated using the Expanded Disability Status Scale (EDSS), in which pyramidal functional scores were used for further analysis. Patients were divided in two groups according to the pyramidal functional scores: ≤3 with normal to moderate paraparesis or hemiparesis, and ≤3 with severe paraparesis or hemiparesis. Serum cytokines were measured using sandwich enzyme-linked immunosorbent assay. Results: As expected, MS patients with pyramidal functional scores >3 were older than those with scores ≤3 (p=0.0266). They also presented higher EDSS scores, disease progression, and frequency of secondary progressive and primary progressive MS clinical forms than those with pyramidal functional scores ≤3 (p<0.0001, p<0.0001, and p=0.0187, respectively). However, increased IFN-γ levels and decreased IL-4 levels were associated with MS patients that presented pyramidal functional scores >3 (p=0.0423 and p=0.0288, respectively). Moreover, a positive correlation was found between the pyramidal functional scores and IFN-γ levels(r=0.2275, p=0.0102). Discussion and Conclusion: Taken together, the results suggest that the cytokine imbalance toward the Thl immune response, characterized by the increased IFN-γ and decreased IL-4, may exert and an important role in involvement of the pyramidal functional system that could reflect in the disability, disease progression, and clinical forms. The results also suggest that disability in secondary progressive MS patients could be related to the progressive involvement of the pyramidal functional system. [ABSTRACT FROM AUTHOR]

Introduction: Although inflammation is the driving force for brain injury in multiple sclerosis (MS), studies suggest that different pathological mechanisms modulate the lesions in relapsing-remitting multiple sclerosis (RRMS) and progressive MS clinical forms. The aim of this study was to evaluate the role of redox and the cytokine profile in progressive forms of MS. Materials and Methods: A total of 126 RRMS and 34 progressive MS patients were recruited. Disability was assessed using the Expanded Disability Status Scale (EDSS) and disease activity was evaluated using magnetic resonance imaging (MRI) with gadolinium. Serum cytokines were measured by sandwich enzyme-linked immunosorbent assay; hydroperoxide (CL-LOOH) was evaluated by chemiluminescence. Results: Progressive MS differed from RRMS in disease duration, EDSS baseline, EDSS five-year follow-up, and increased disease activity when compared with RRMS (p<0.0001). Progressive MS presented increased levels of IL-1B (p=0.0168) and IFNG (p=0.0374), and lower levels of IL-12 (p=0.0006) than RRMS; and a predominance of cytokines with Thl/Th2 profile (IFNG/IL4, p=0.0033; IFNG/IL-10, p<0.0001). Multivariate analysis showed that IFNG was independently associated with progressive MS (p=0.0105). In relation to oxidative stress markers, patients with progressive MS presented increased levels of hydroperoxide (p=0.0408), NOx (p=0.0327), AOPP (p=0.0141), and carbonyl protein (p=0.0195), whilst for antioxidant defense, they presented decreased TRAP (p=0.0489). Discussion and Conclusion: This study revealed a complex cytokine network and redox state imbalance among patients with progressive MS that was correlated with a progressive clinical course of the disease. Oxidative stress may be able to initiate a cascade of reactions affecting the function of several proteins that progressively become impaired and culminate in relapse outburst. At this level, severe disability and inflammatory events occur and oxidative damage seems to affect inflammatory pathways. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is an autoimmune mediated disease in which diet and obesity are implicated as risk factors. Immune responses are influenced by molecules produced by immune and fat cells, called cytokines and adipokines, respectively. Adiponectin is an adipokine with anti-inflammatory effects and modulates the natural T regulatory cells (nTreg) function. The aim of this study was to evaluate serum cytokine and adipokine levels in relapsing-remitting MS (RRMS) patients according to their tumor necrosis factor beta (TNFB) Ncol polymorphism. Materials and Methods: Demographic and clinical data were obtained from 169 RRMS patients. Disability was evaluated using the Expanded Disability Status Scale (EDSS) and disease activity was assessed using resonance magnetic imaging (RMI) with gadolinium. Serum cytokines and adiponectin levels were measured by a sandwich enzyme-linked immunosorbent assay. TNFB Ncol polymorphism was evaluated using PCR-RFLR Factors such as age, gender, ethnicity, and BMI were controlled between TNFB Ncol genotype groups. Results: Patients with RRMS carrying the TNFB2/B2 genotype presented increased levels of TNFA (p=0.0465) and IFNG (p=0.0226); and decreased levels of IL-4 (p=0.0462), IL-10 (p=0.0083), and adiponectin (p=0.0418). The EDSS did not differ according to the TNFB Ncol genotypes (p=0.9638). However, patients carrying the TNFB2/B2 genotype presented increased frequency of positive gadolinium enhanced lesions (p=0.0429). Discussion and Conclusion: These data showed that TNFB Ncol polymorphism was associated with increased pro- and inflammatory cytokines and decreased anti-inflammatory cytokines and adiponectin levels, and with disease activity, suggesting that may play a part in cytokine and adiponectin expression, and consequently, in MS activity. Considering that inflammatory cytokines and adiponectin exert antagonist effects, these results may suggest a relationship between this genetic marker and the modulation of the inflammatory process in MS. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown an association between low levels of vitamin D and greater disability in multiple sclerosis (MS) patients, as evaluated by the Expanded Disability Status Scale (EDSS). Previous research has demonstrated that oxidative stress is associated with disease progression. It has further been shown that vitamin D acts as an immunomodulator and antioxidant, and its deficiency could be associated with increased oxidative stress and disability in these patients. The aims of the present study was to assess serum concentrations of 25-hydroxyvitamin D and oxidative stress markers, and to verify their correlation with disability in MS patients. Materials and Methods: This study included 107 patients with relapsing-remitting multiple sclerosis (RRMS), of which 68 (63.5%) were female and 39 (36.5%) male, with a mean age of 43 years (range, 19-72 years). Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein product (AOPP) and nitric oxide metabolites (NOx). The measurements of 25-hydroxyvitamin D was performed by chemiluminescence microparticle immunoassay (CMIA) and patients with values <30 ng/mL were considered vitamin D deficient. All the RRMS patients were clinically evaluated for disability using the EDSS and were divided into two groups according to vitamin D levels. All patients were under treatment with interferon beta-la or -lb, and all were in remission. Results: MS Patients with vitamin D deficiency showed higher levels of NOx (p=0.003) and lipid hydroperoxide (p=0.038) when compared with patients with vitamin D levels >30 ng/mL. Regarding AOPP, there was no statistical difference in either group. A negative correlation was observed between serum concentrations of vitamin D and the EDSS (r= -0.244, p=0.011). Discussion and Conclusion: These data suggest that hypovitaminosis D may be involved in the redox imbalance presented by patients with MS and this may participate in the pathophysiology of MS progression. [ABSTRACT FROM AUTHOR]

In addition to increased levels of TNF-α, the oxidative stress may also be involved in the pathophysiology of multiple sclerosis (MS). The B2/B2 genotype of TNF-β NcoI genetic polymorphism was associated with increase TNF-α expression and this may lead to an imbalance between oxidant and antioxidant molecules leading to the oxidative stress. The aim of this study was to evaluate the association between TNF-β NcoI genotypes and the oxidative stress and inflammatory biomarkers in MS patients. The genomic DNA was obtained from 166 MS patients from Southern Brazil population. TNF-β NcoI genotypes were obtained using polymerase chain reaction and restriction fragment length polymorphism. The oxidative stress was evaluated by plasma levels of lipid hydroperoxide, carbonyl protein, nitric oxide metabolites (NOx), sulfhydryl group of proteins, serum uric acid levels, and total radical-trapping antioxidant parameter (TRAP). Serum cytokines (TNF-α, IFN-g, and IL-17) were measured using ELISA. The age, gender, ethnicity, smoking, and body mass index did not differ among the patients carrying the B2/B2 and B1/ B2+B1/B1 genotypes (p>0.05). MS patients carrying B2/B2 genotype presented higher TNF-α (p=0.0358) levels and lower NOx (p=0.0462) levels and TRAP (p=0.0209) than patients with other genotypes. The values of hydroperoxide, carbonyl protein, sulfhydryl group of proteins, and serum uric acid levels did not differ according to the genotypes of the MS patients (p>0.05). No difference was also observed in the assessed biomarkers obtained from female MS patients carrying the B2/B2 genotype (p>0.05). However, male MS patients carrying the B2/B2 genotype presented higher TNF-α (p=0.0435), IFN-γ (p=0.0351), IL-17 (p=0.0326), hydroperoxide (p=0.0402), and sulphydryl group (p=0.0116) levels, and lower NOx (p=0.0243) and TRAP (p=0.0343) levels than male MS patients with other genotypes. These results suggest that the B2/B2 genotype of TNF-β NcoI polymorphism is associated with increased levels oxidative stress biomarkers and increased TNF-α, IFN-g, and IL-17 cytokines; and may play an important role in the physiopathology of the disease in male MS patients. [ABSTRACT FROM AUTHOR]

TNF-β NcoI genetic polymorphism has been associated with increase in the TNF-α expression which could be an important factor in the pathogenesis of multiple sclerosis (MS).The aim of this study was to evaluate the association between TNF-β NcoI genotypes and inflammatory and metabolic biomarkers in MS patients. Demographic and clinical data were obtained from 166 MS patients. The disability was evaluated using the Expanded Disability Status Scale (EDSS). Peripheral blood samples were collected to measure cytokines, C reactive protein (CRP), adiponectin, glucose, insulin, homocysteine, and lipid profile. The homeostasis model assessment for insulin resistance (HOMA-IR) was obtained. TNF-β NcoI genotypes were evaluated using PCR-RFLP. Female with MS carrying the B2/B2 genotype presented higher glucose (p=0.0419), and insulin (p=0.0256) levels, and insulin resistance (p=0.0509) than female B1/B2+B1/B1. A positive correlation was observed between EDSS and glucose levels (r=0.2879, p=0.0366), and HOMA-IR (r=0.2879, p=0.0366) in woman carrying B2/B2 genotype. Otherwise, male MS patients carrying the B2/B2 genotype presented higher levels of TNF-α (p=0.0435), IFN-γ (p=0.0351), and IL-17 (p=0.0326), and decreased levels of IL-4 (p=0.0329) and IL-10 (p=0.0424) than male carrying B1/B2+B1/B1. A positive correlation was observed between EDSS and TNF-α levels (r=0.5084, p=0.0157) in men carrying B2/B2 genotype. Male patients carrying B2/B2 genotype presented increased levels of TNF-α (p=0.0398), IFN-γ (p=0.0406), IL-17 (p=0.0291), and decreased levels of hsCRP (p=0.0237) and adiponectin (p=0.0530) compared with female MS patients carrying B2/B2 genotype. Female carrying B2/B2 genotype presented increased triglyceride levels (p=0.0008), systolic blood pressure (p=0.0116), insulin (0.0171), and HOMA-IR (p=0.0239) compared with male carrying B2/B2 genotype. The results suggest that the association between TNF-β NcoI polymorphism and inflammatory and metabolic biomarkers differs according to the gender of MS patients. While an association between metabolic biomarkers that could contribute to high disability and worse clinical course was observed among females, an association between inflammatory biomarkers that could lead to high disability and worse clinical course was observed among males. [ABSTRACT FROM AUTHOR]

Background: The demyelinating lesions of multiple sclerosis (MS) cause many impairments. Fatigue is one of the most common symptoms in MS that can negatively influence the quality of life. The Wii therapy system consists of a set of games developed with the goal of providing users with an easy way to perform physical activities, such as aerobic games. Objective: To evaluate the effect of aerobic games via Wii therapy on MS fatigue. Methods: Fifteen MS patients were selected with the inclusion criteria: relapsing-remitting MS, no relapses in the last 3 months, cognitive preserved, independent gait, no heart dysfunctions and no balance deficit according to the Berg scale. The intervention was performed twice a week for 4 weeks using a Wii therapy protocol (Wii fit Nintendo®), composed of games using a balance board that simulate running and aerobic exercises with virtual obstacles. The patients were assessed both pre- and post-intervention by means of a 6 minute walking test (WT6) and a fatigue severity scale (FSS). Data were analyzed using SPSS software, considering a statistical significance level when p < 0.05. Results: The sample composed of 12 women and 3 men, mean age 37.4 ± 2.7 years, mean EDSS score of 3.0 ± 1.8 points and mean MS diagnosed duration 5.8 ± 3.2 years. The mean pre-intervention FSS and WT6 results were 36 ± 3.9 points and 431 ± 107.78 m, respectively. The mean post-intervention FSS and WT6 results were 31 ± 1.9 points and 543 ± 85 m. Comparing the pre- and post-intervention outcomes, there was an improvement in fatigue (p=0.04) and exercise capacity (p=0.05). Conclusion: Aerobic training via Wii therapy is an effective method for reducing fatigue in MS. [ABSTRACT FROM AUTHOR]

Background: Physical fatigue is common and is the most disabling symptom in Multiple sclerosis (MS). Fatigability can also occur with or without fatigue, but it is less intense. Objective: To determine the influence of physical fatigue and fatigability on motor control of MS patients. Methods: A cross-sectional study was carried out involving 70 MS patients followed at the outpatient clinic of the university hospital of the State University of Londrina, Parana. The patients were assessed using the fatigue severity scale, isotonic handgrip and isometric exercises with dynamometer to analyze fatigability, and the 9-Hole Peg Test (9-HPT) to evaluate motor control of the upper limbs. The sample was categorized into four groups: G1=subjects with fatigue; G2= subjects with fatigability; G3 = subjects with fatigue and fatigability; G4 = no fatigue and fatigability. SPSS software (version 15.0) was used for the statistical analysis, considering a p-value ≤ 0.05. Results: The sample was predominantly female (85%) and presented in categories as: G1=28; G2=13; G3=21 and G4=8 subjects. G1 revealed 69% of subjects with severe fatigue. The groups G1 and G3 demonstrated significantly worse outcomes in motor control of the upper limbs (G1 p= 0.03; G3 p= 0.05), however fatigability was not correlated (G2 p=0.07). The most severe fatigue level was associated with motor control difficulties, but without statistical significance (G1 p= 0.06). Conclusion: Physical fatigue affects the mobility and compromises motor control of MS patients. [ABSTRACT FROM AUTHOR]

Background: Fatigue is one of the most common and disabling symptoms in multiple sclerosis (MS) that may affect 70-90% of patients. There are some aspects that may influence the beginning and/or the exacerbation of fatigue symptom. Objective: To identify clinical characteristics associated with fatigue in MS and the associations of sociodemographic and clinical variables to these patterns. Methods: A sample of 181 MS patients was followed continuously during twelve months. A clinical questionnaire, Hospital Anxiety and Depression scale, and Epworth scale were applied at the initial face-to-face assessment and the fatigue severity scale (FSS) was administered via phone call every month. Three patterns of fatigue were defined: persistent fatigue (PF) (mean FSS score ≥ 5 at all time-points), sporadic fatigue (SF) (mean FSS score ≥ 5 at one or two time-points), and no fatigue (mean FSS score < 5 at all time-points). SPSS software (version 15.0) was used for the statistical analyses, considering a significance level of 5%. Results: Of the 181 MS patients, 87 [48%, 95% confidence interval (CI) 32-44] showed persistent fatigue, 63 [34.8% CI 31-43] sporadic fatigue and 31 [17.1% CI 20-31] had no fatigue. Persistent fatigue was more common with increased neurological impairment (p < 0.001), primary progressive MS (p= 0.01), insomnia (p= 0.03), heat sensitivity (p= 0.03), sudden-onset fatigue (p < 0.001), mood disturbance (p= 0.07), and beginning pharmacotherapy for fatigue (p= 0.04), compared with patients without fatigue. Multivariable analysis showed that heat sensitivity (PF p= 0.02, SF p= 0.04) and physical impairment (PF p= 0.03, SF p= 0.06) were more associated with PF, but not depression (PF p= 0.06, SF p= 0.08). Conclusion: Multivariable analyses confirmed a significant association between heat sensitivity, insomnia, physical impairment, physical fatigue and PF. [ABSTRACT FROM AUTHOR]

Background: The 9-item Fatigue Severity Scale (FSS) has been widely used as an outcome measure in multiple sclerosis (MS). Modern psychometric theory, such as the Rasch measurement model, has set new quality standards for outcome measures by appraising a broad range of measurement properties, besides the reliability and validity emphasized by classical test theory. Objective: To assess if the Portuguese version of FSS is a valid instrument to assess fatigue in Brazilian MS patients. Methods: A cross-sectional study involving a sample of 181 MS outpatients who were assessed using the Expanded Disability Status Scale (EDSS) and FSS (Portuguese version). Rasch analysis was performed using RUMM 2020 software (version 4.1). Results: The FSS failed to meet Rasch model expectations. Three items did not fit the Rasch model, with one showing poor discrimination across the scale and the other two items showing bias for factors such as age, sex, degree of disability and disease type. Removal of these three items provided a valid 6-item Rasch scale (FSS-6) that satisfied strict tests of unidimensionality. Conclusion: The Portuguese version of the FSS with 9 items is invalid. The 6-item version after the Rasch model seems more adequate for measuring fatigue. Studies using the 9-item FSS may need to be re-evaluated using the FSS-6 to analyze fatigue. [ABSTRACT FROM AUTHOR]

Background: The ability to determinate minimum clinically important differences (MCID) is a relevant aspect of a scale. The higher the responsiveness of an instrument, the better will be its ability to measure changes and to be used prognostically. The Modified Fatigue Impact scale (MFIS) is widely used to assess fatigue in multiple sclerosis (MS) patients. Objective: To determine if the MFIS is able to detect minimum changes and if it according to the MS subject's perception. Methods: 112 MS patients were enrolled on this cohort study but only 80 were followed over the course of twelve months. Each patient was interviewed once a month using the MFIS and global perceived change was assessed by asking the simple question of 'compared to 4 weeks ago, my fatigue is'; with five response options of 'much better', 'better', 'the same', 'worse' or 'much worse'. The changes were determined as improvement (decrease of fatigue) or no changes. The decrease of fatigue was observed with the following possible interventions: pharmacotherapy for fatigue, corticosteroid treatment for relapses and participation in a fatigue rehabilitation program. All interviews were performed by telephone call. SPSS software (version 15.0) was used for the statistical analyses, considering a significance level of 5%. Results: The MCID for MFIS was relatively small. The overall change scores of the MFIS were accorded with the perceived direction of change. Importantly, no change was seen when none was perceived. Using the interval level MFIS scores, the largest MCID equated to 2.44 points on the Physical domain, 0.84 points on the Cognitive domain and 0.97 on the Psychic and social domain. Conclusion: MFIS responds as expected to changes in fatigue and has desirably small MCID scores. [ABSTRACT FROM AUTHOR]

Previous studies have shown that inflammatory and metabolic biomarkers may be associated with demyelinating diseases of the central nervous system. The aim of this study was to evaluate inflammatory and metabolic biomarkers in patients with neuromyelitis optica (NMO), and multiple sclerosis (MS). Demographic and clinical data were obtained from 16 NMO and 41 MS patients, and 50 healthy controls. The disability of the NMO and MS patients was evaluated using the Expanded Disability Status Scale (EDSS). Peripheral blood samples were collected to measure C-reactive protein (CRP), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), glucose, and insulin. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. All NMO patients were female and, therefore, the MS patients and controls were gender-matched. Characteristics such as age, ethnicity, body mass index, and smoking history were also controlled (p≥0.05). No difference was found in CRP levels between the groups (p≥0.05). MS patients presented higher total cholesterol levels compared with controls (p=0.0021). NMO and MS patients presented higher triglycerides levels (p=0.0044), insulin (p= 0.0070), and HOMA-IR (p= 0.0055) compared with controls. NMO patients presented higher EDSS than MS patients (p=0.0052). High insulin levels (p= 0.0206) and HOMA-IR (p= 0.0607) were independently associated with NMO, while none of the variables were independently associated with MS. Among the NMO patients, a negative correlation was observed between EDSS and glucose levels (r=-0.6349, p= 0.0147) and a positive correlation was observed between EDSS and insulin levels (r= 0.5858, p= 0.0354). The results suggest that metabolic biomarkers may be associated with NMO, with insulin and HOMA-IR independently associated with the disease. Moreover, low levels of glucose and hyperinsulinemia were associated with disability of NMO patients. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system that has a worldwide distribution. The aim of this study was to report demographic and clinical features of patients with NMO from Southern Brazil. Demographic and clinical data were obtained from 16 patients with NMO using a standard questionnaire and from medical records. All patients were female: 5 (31.3%) Caucasian; 9 (14.4%) Mullato (mixed race); and 2 (12.5%) Black. The median age was 44.5 years, the median age at disease onset was 36 years, and the median disease duration was 7 years. Fifteen (93.8%) patients presented a relapsing course and 1 (6.2%) a monophasic course. The initial event was myelitis in 6 (37.5%) women, bilateral optic neuritis in 3 (18.8%) and unilateral optic neuritis in 4 (25.0%) women, simultaneous myelitis and bilateral optic neuritis in 1 (6.2%), and simultaneous myelitis and unilateral optic neuritis in 2 (12.5%) women. The second event was myelitis in 7 (43.8%), bilateral optic neuritis in 1 (6.2%), and unilateral neuritis in 4 (25.0%) patients, with 4 (25.0%) not presenting this data. According to magnetic resonance imaging data of the first myelitis, 4 (25.0%) presented cervical lesions, 5 (31.4%) presented thoracic lesions, 4 (25.0%) presented cervical and thoracic lesions, 2 (12.4%) presented cervical lesions extending into the medulla oblongata, and 1 (6.2%) presented lesions in all spinal segments. Four (25.0%) of the women presented associated autoimmune diseases (juvenile rheumatoid arthritis, hypothyroidism, systemic lupus erythematosus and scleroderma), 1 (6.2%) presented arterial hypertension, 1 (6.2%) presented depression, and 10 (62.6%) had no associated disease. Five (31.3%) patients presented positive NMO-IgG, 6 (37.4%) negative NMO-IgG, and 5 (31.3%) were not evaluated for this marker. Demographic and clinical characteristics of NMO patients from Southern Brazil are in agreement with previous studies worldwide reported in the scientific literature. [ABSTRACT FROM AUTHOR]

Although inflammation is the driving force for brain injury in multiple sclerosis (MS) patients, independently whether the patients experience a relapsing-remitting MS (RRMS) or progressive course of their disease, different mechanisms have been proposed to explain the pathogenesis of progressive MS. The aims of this study were to evaluate the serum TNF-α, IL-1β, IL-6, IL-12, IFN-γ, IL-17, IL-4, and IL-10 levels in patients with progressive MS, and their association with disease progression. Demographic and clinical data, and serum samples were obtained from 32 patients with progressive MS [9 with primary progressive MS (PPMS) and 25 with secondary progressive MS (SPMS)], 126 patients with RRMS, and 40 healthy controls from Southern Brazil. The serum cytokine level was assessed using enzyme linked-immunosorbent assay. The disability of MS patients and progression of the disease were evaluated using the Expanded Disability Status Scale (EDSS). The activity of the disease was evaluated using the resonance magnetic imaging (MRI) with gadolinium. Serum IL-Iβ, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in patients with progressive MS than controls (p<0.05). High serum IL-I-β, IL-6, and IL-4 levels were independently associated with progressive MS (p<0.05). Increased IL-1 and IFN-β levels, and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS (p<0.05). Patients with progressive MS with progression presented increased IFN-γ and IL-10 levels than those with progressive MS without progression (p<0.05). Patients with progressive MS that exhibited disease progression presented higher frequency of positive enhanced lesions in MBI, higher IL-I-β, IFN-γ, and IL-17, and lower IL-12 levels than RHMS patients (p<0.05). The results underscore the complex cytokine network imbalance exhibited by the patients with progressive MS and that IL-10 levels were inversely associated with the disability of the disease. Increased TNF-α, IFN-γ, and IL-17 levels were supposed to be involved with the progressive forms of MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neurological disease characterized by inflammation and demyelination in the central nervous system. Hyperhomocysteinemia has been associated with neurodegenerative disorders, such as MS and Alzheimer disease, and it seems to contribute to neurological decline in MS. The aims of this study were to evaluate the plasma homocysteine levels in MS patients and to verify whether homocysteinemia is associated with disability and oxidative stress biomarkers. This study included 127 MS patients and 199 healthy individuals from the same geographic area, who presented no clinical or laboratory characteristics of autoimmune diseases. The disability of MS patients was evaluated using the Expanded Disability Status Scale (EDSS). Parameters such as age, gender, ethnicity, smoking history, and body mass index (BMI) were controlled. Oxidative stress was evaluated by t-butyl hydroperoxide-initiated chemiluminescence (lipid hydroperoxide), carbonyl protein, and nitric oxide metabolites (NOx). The MS patients presented higher plasma homocysteine levels (p=0.032) and oxidative stress biomarkers, including lipid hydroperoxide (p<0.0001) and carbonyl protein (p=0.0006), than the controls. Plasma NOx levels were lower among the MS patients than the controls (p<0.0001). MS patients with hyperhomocysteinemia showed increased oxidative stress biomarkers in plasma, including lipid hydroperoxide (p=0.038) and carbonyl protein (p=0.035). MS patients with hyperhomocysteinemia presented higher EDSS scores than MS patients with normal plasma homocysteine levels; however this difference was not significant (p=0.136). A positive correlation was observed between plasma homocysteine and carbonyl protein (r=0.293, p=0.020) levels and between homocysteine and NOx (r=0.376, p=0.002) levels. These results underscore that hyperhomocysteinemia is associated with oxidative stress in patients with MS, and that this metabolic change could contribute to the progression of disability of MS patients. [ABSTRACT FROM AUTHOR]

In addition to increased levels of TNF-α, oxidative stress may also be involved in the pathophysiology of multiple sclerosis (MS). The B2/B2 genotype of TNF-β NcoI genetic polymorphism is associated with an increase in TNF-α expression and this may lead to an imbalance between oxidant and antioxidant molecules, leading to the oxidative stress. The aim of this study was to evaluate the association between TNF-β NcoI genotypes and oxidative stress and inflammatory biomarkers in MS patients. The genomic DNA was obtained from 166 MS patients from a Southern Brazil population. TNF-β NcoI genotypes were obtained using polymerase chain reaction and restriction fragment length polymorphism. Oxidative stress was evaluated by plasma levels of lipid hydroperoxide, carbonyl protein, nitric oxide metabolites (NOx), sulfhydryl group of proteins, serum uric acid levels, and total radical-trapping antioxidant parameter (TRAP). Serum cytokines (TNF-α, IFN-γ and IL-17) were measured using ELISA. The age, gender, ethnicity, smoking history, and body mass index did not differ among the patients carrying the B2/B2 and B1/B2+B1/B1 genotypes (p>0.05). MS patients carrying the B2/B2 genotype presented higher TNF-α (p=0.0358) levels and lower NOx (p=0.0462) and TRAP (p=0.0209) levels than patients with other genotypes. The values of hydroperoxide, carbonyl protein, sulfhydryl group of proteins, and serum uric acid levels did not differ according to the genotypes of the MS patients (p>0.05). No difference was also observed in the assessed biomarkers obtained from female MS patients carrying the B2/B2 genotype (p>0.05). However, male MS patients carrying the B2/B2 genotype presented higher TNF-α (p=0.0435), IFN-γ (p=0.0351), IL-17 (p=0.0326), hydroperoxide (p=0.0402), and sulfhydryl group (p=0.0116) levels, and lower NOx (p=0.0243) and TRAP (p=0.0343) levels than male MS patients with other genotypes. These results suggest that the B2/B2 genotype of TNF-β NcoI polymorphism is associated with increased levels of oxidative stress biomarkers and increased TNF-α, IFN-γ and IL-17 cytokines. This may play an important role in the physiopathology of the disease in male MS patients. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by inflammation and demyelination. Studies have reported the role of iron dysregulation in the pathogenesis of MS. The aim of this study was to determine plasma ferritin levels and oxidative stress biomarkers and their correlation with disability of MS patients. This study included 127 MS patients and 199 matched healthy controls. The disability of MS patients was evaluated using the Expanded Disability Status Scale (EDSS) and they were separated in two groups according to an EDSS cut-off value of 3.5. Plasma ferritin levels were evaluated using chemiluminescent assay. Oxidative stress was evaluated by t-butyl hydroperoxide-initiated chemiluminescence (lipid hydroperoxide), carbonyl protein, and nitric oxide metabolites (NOx). The MS patients presented higher plasma levels of ferritin (p<0.0001) and oxidative stress biomarkers, including lipid hydroperoxide (p<0.0001) and carbonyl protein (p=0.0006), than the controls. The plasma levels of NOx were lower among the MS patients than controls (p<0.0001). MS patients with an EDSS > 3.5 (high disability) showed higher plasma levels of ferritin (p=0.035) and oxidative stress biomarkers, including lipid hydroperoxide (p=0.013) and carbonyl protein (p=0.021), than MS patients with an EDSS ≤3.5 (low disability). Plasma levels of ferritin were higher among patients with progressive MS than those with relapsing-remitting MS, however, this difference was not significant (p=0.823). A positive correlation was observed between plasma levels of ferritin and EDSS (r=0.2144; p=0.0187). These results suggest that hyperferritinemia is associated with disability in MS and could be a useful inflammatory biomarker for progression of the disease. [ABSTRACT FROM AUTHOR]