Nebojsa Stojsavljevic

The impact of sexual dysfunction on the quality of life measured by MSQoL-54 in patients with multiple sclerosis:

Objective Sexual dysfunction (SD) is a common but often overlooked symptom in multiple sclerosis (MS). The aim of this study was to estimate the frequency, type, and intensity of SD in our patients with MS and to investigate its influence on all the domains of quality of life. Methods The study population comprised a cohort of 109 patients with MS (McDonalds criteria, 2001). SD was quantified by a Szasz sexual functioning scale. Health-related quality of life was measured by a disease-specific instrument MSQoL-54 (Serbian version). Results The presence of at least one symptom of SD was found in about 84% of the men and in 85% of the women. The main complaints in women were reduced libido, difficulties in achieving orgasm, and decreased vaginal lubrication; in men, the main complaints were reduced libido, incomplete erections, and premature ejaculation. In women, statistically significant negative correlations between the presence and level of SD and quality of life domains were reached for all subscales (P < 0.01), except for the Pain subscale (P = 0.112). In men, negative correlations were also observed for all domains, but they were statistically significant for physical health, physical role limitations, social function, health distress, sexual function, and sexual function satisfaction (P < 0.01). We found that the presence of all the analyzed types of sexual problems statistically significantly lowered scores on the sexual function and the sexual function satisfaction subscales in both men and women (P < 0.01). The most prominent impact on both domains was observed for the total loss of erection in men and for anorgasmia in women. Conclusions Our results reveal that frequent occurrence of SD in MS patients prominently affects all aspects of their quality of life.

Uric acid levels in sera from patients with multiple sclerosis

Abstract The levels of uric acid (UA), a natural peroxynitrite scavenger, were measured in sera from 240 patients with multiple sclerosis (MS) and 104 sex- and age-matched control patients with other neurological diseases (OND). The mean serum UA concentration was lower in the MS than in the OND group, but the difference did not reach the level of statistical significance (P=0.068). However, the mean serum UA level from patients with active MS (202.6+67.1 μmol/l) was significantly lower than that in inactive MS patients (226.5+78.6 μmol/l; P=0.046) and OND controls (P=0.007). We found a significant inverse correlation of serum UA concentration with female gender (P=0.0001), disease activity (P=0.012) and duration (P=0.017), and a trend towards an inverse correlation with disability as assessed by EDSS score, which did not reach statistical significance (P=0.067). Finally, multivariate linear regression analyses showed that UA concentration was independently correlated with gender (P=0.0001), disease activity (P=0.014) and duration of the disease (P=0.043) in MS patients. These findings suggest that serum UA might serve as a possible marker of disease activity in MS. They also provide support to the potential beneficial therapeutic effect of radical-scavenging substances in MS.

Lifestyle Factors and Multiple Sclerosis: A Case-Control Study in Belgrade

The aim of this case-control study was to assess the risk of developing multiple sclerosis (MS) associated with certain lifestyle factors (cigarette smoking and coffee and alcohol consumption). The study groups consisted of 210 cases with clinically proven and/or laboratory-confirmed MS (Poser’s criteria) and an identical number of sex- and age-matched hospital controls. In the MS patients, cigarette smoking was significantly more frequent than in the controls (OR = 1.6, p = 0.021). A dose-response relationship between the risk of MS and both duration (years) of smoking (p = 0.027) and number of cigarettes smoked daily (p = 0.021) was observed. Coffee consumption was significantly more frequent in the MS group (OR = 1.7, p = 0.047), with dose-response relationships. The analysis of alcohol drinking showed a significant association between consumption of hard liquor per day and risk of MS (OR = 6.7, p = 0.026). In multivariate logistic regression analysis, smoking was detected to be a significant independent risk factor for MS (OR = 2.4, p = 0.004).

Interleukin-12 and tumor necrosis factor-α levels in cerebrospinal fluid of multiple sclerosis patients

Concentrations of interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) were measured in patients with multiple sclerosis (MS) and control patients with non-inflammatory neurological diseases (NIND) by an enzyme-linked immunosorbent assay. TNF-alpha was detectable in the CSF of 60% of the patients with active MS, none of those with inactive MS and 29% of patients with NIND. CSF concentrations of TNF-alpha correlated with the degree of disability in MS patients (P < 0.05). Detectable levels of IL-12 were found in 10% of the MS CSF samples and 18% of NIND CSF samples. There was a significant relationship between CSF concentrations of IL-12 and those of TNF-alpha in MS patients (P < 0.05); no relationship was observed between the presence of IL-12 and disease activity or severity. These findings further stress the involvement of T helper 1 type-response within the central nervous system in MS.

The analysis of IL-1 beta and its naturally occurring inhibitors in multiple sclerosis: The elevation of IL-1 receptor antagonist and IL-1 receptor type II after steroid therapy

The aim of our investigation was to analyze the pattern of interleukin-1 (IL-1) family compounds: IL-1 beta, IL-1 receptor accessory protein (Acp), IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type II (IL-1RII) in the serum and cerebrospinal fluid (CSF) from 67 multiple sclerosis (MS) patients and 31 controls. We found significantly elevated CSF levels of IL-1 beta, IL-1Ra and Acp in MS patients compared to controls (p=0.001), while IL-1 beta and Acp were significantly elevated in MS sera (p=0.001). IL-1Ra and/or IL-1 RII increased in sera of all 10 investigated patients after the steroid treatment for relapse. Our findings suggest the important beneficial role of the induction of IL-1 RII and IL-1Ra in MS.

A 44-month clinical-brain MRI follow-up in a patient with B12 deficiency

We report a 51-year-old woman with vitamin B12 deficiency who presented with slight megaloblastic anemia and severe neurologic deficits associated with multiple focal and confluent T2-weighted white matter hyperintensities on brain MRI. Forty-four months after initiation of hydroxocobalamin therapy, there was clinical improvement and striking reduction in the MRI abnormalities. B12 deficiency should be considered in the differential diagnosis of neurologic disorders associated with multiple areas of white matter hyperintensities on T2-weighted brain MRI.

Expression of Th1 and Th17 cytokines and transcription factors in multiple sclerosis patients: does baseline T-bet mRNA predict the response to interferon-beta treatment?

We studied the effect of one-year interferon (IFN)-beta treatment on the in vivo mRNA expression of IFN-gamma, interleukin (IL)-17, T-bet and RoR-gammat, on peripheral blood mononuclear cells (PBMC) from 36 multiple sclerosis (MS) patients. In the total MS group, IFN-beta induced decrease in mRNA levels of IFN-gamma and T-bet (p<0.0001), while the levels of IL-17 and RoR-gammat remained similar. In both responders and non-responders, IFN-beta induced significant decrease of IFN-gamma (p<0.0001 and p=0.011, respectively), while decrease in T-bet was detected only in responders (p<0.0001). Higher pre-treatment T-bet allowed prediction of the clinical response in the first year (beta=0.601, p=0.036). Our preliminary findings suggest that T-bet expression might be a potential prognostic marker of treatment response to IFN-beta in MS.

Temporal dynamics of cerebrospinal fluid anti-aquaporin-4 antibodies in patients with neuromyelitis optica spectrum disorders

Neuromyelitis optica spectrum disorders (NMOSD) are associated with anti-aquaporin-4 autoantibodies (AQP4-IgG). Limited data is available on longitudinal cerebrospinal fluid (CSF) AQP4-IgG and their relation to disease activity and inflammatory parameters. AQP4-IgG titers were measured in matched longitudinal serum and CSF samples of 12 patients with NMOSD by an immunofluorescence assay and correlated with clinical parameters. CSF AQP4-IgG were present in patients with high serum titers and correlated with spinal MRI lesion length and CSF parameters. Clinical improvement was associated with a decrease in CSF, but not serum, AQP4-IgG titers. Thus, CSF AQP4-IgG were associated with clinical activity and neuroinflammation.

Antibodies against myelin oligodendrocyte glycoprotein in the cerebrospinal fluid of multiple sclerosis patients

Antibodies against myelin oligodendrocyte glycoprotein (MOG) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) in different animal species and are implicated in the immunopathogenesis of multiple sclerosis (MS). In order to evaluate the anti-MOG response, we have analyzed the cerebrospinal fluids (CSFs) from 44 MS patients and 51 controls, 11 with other inflammatory neurological disorders (OIND) and 40 with non-inflammatory neurological disorders (NIND). The frequency of anti-MOG antibodies positive patients in the MS group (30%) was significantly higher compared to the NIND (8%, p=0.02), but not compared to the OIND group (55%, p=0.228). Interestingly, all six patients with neurosarcoidosis had MOG-specific antibodies in their CSF. Frequency of anti-MOG antibodies was similar in patients with clinically active and stable MS (32% and 26%, respectively; p=0.921). However, in clinically active MS patients, antibody titers were higher in comparison with patients with stable disease, although the difference did not reach the level of statistical significance (p=0.06). These results further support the potential role of anti-MOG antibodies in the immunopathology of MS in the subset of patients with this disease. Furthermore, our findings suggest for the first time that anti-MOG antibodies could be an accessory diagnostic tool in neurosarcoidosis.

Nitric oxide metabolites and interleukin‐6 in cerebrospinal fluid from multiple sclerosis patients

Interleukin‐6 (IL‐6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 patients with MS and 23 control subjects. Mean CSF IL‐6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL‐6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL‐6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL‐6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.