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Objective To examine whether self-rated physical health, as measured by the Physical Functioning Scale (PF) and the Role-physical Scale (RF) of the SF-36 Health Survey, could predict change in disability measured by the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS) over a follow-up period of 3 years. Methods A group of 156 clinically definite MS patients (Poser criteria), who had never been treated with disease-modifying therapies, were recruited consecutively from an outpatient clinic setting at the Institute of Neurology, Belgrade. The self-rated physical health was measured by using PF and RF of the SF-36. Results At follow-up, 33 out of 156 patients (21%) had dropped out. The mean EDSS score had increased from 3.7 to 4.5. Multiple regression analyses using change in EDSS as the dependent variable and baseline scores of EDSS and RF as independent variables showed a significant effect for RF (standardized beta = -0.21). A similar but non-significant effect was found for PF. Dichotomizing change in disability according to clinically meaningful deterioration and using logistic regression, an odds ratio of 1.27 (95% confidence interval 1.01-1.62) was found for the smallest unit of change in the self-rated scale. This means that patients who rated their own physical health as poor had a higher increase in disability compared with patients with the same level of disability at baseline who rated their physical health better. Conclusions MS patients' perception of their health comprises information predictive for disease development not included in the more objective measure of disability status. [ABSTRACT FROM AUTHOR]

Objectives – The aim of this investigation was to evaluate factors that might influence the health-related quality of life (HRQoL) in multiple sclerosis (MS) patients in Serbia. Materials and methods – This cross-sectional study was performed on a group of 156 patients with MS. HRQoL was assessed by using the SF-36 questionnaire. Expanded Disability Status Scale (EDSS) and Beck Depression Inventory (BDI) scale were assessed as variables affecting the HRQoL of MS patients. Results – EDSS score correlated negatively with all SF-36 health dimensions, and the highest statistically significant coefficients were for physical functioning ( r = −0.682), and social and role functioning ( r = −0.407 and −0.405 respectively). BDI correlated statistically significantly negatively ( P < 0.01) with all SF-36 health dimensions. Conclusions – Our findings suggest that both disability and depression significantly influence the HRQoL in Serbian MS patients, with depressive symptoms having the major influence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A growing body of evidence implicates excessive generation of nitric oxide (NO) within the central nervous system (CNS) in multiple sclerosis (MS). The aim of our study is to analyse nitrite and nitrate as end products of NO in the cerebrospinal fluid (CSF) from MS patients and correlate the concentrations with clinical characteristics of the disease. CSF nitrite and nitrate concentrations were measured after reduction of nitrate, by Griess reaction, in 105 MS patients, 27 patients with non-inflammatory neurological disorders (NIND) and 13 individuals without neurological disorder (Co). Mean CSF nitrite and nitrate concentrations were significantly higher in patients with MS and NIND compared with the Co patients (9.44 and 8.68, respectively, versus 6.85 μM; P=0.0001 and P=0.031, respectively). There was no significant correlation between CSF nitrite and nitrate concentrations and activity, phase, severity and duration of MS. Our data are in agreement with the results of previous studies which have demonstrated raised concentrations of CSF NO metabolites in MS patients, providing further evidence for NO involvement in MS. The lack of correlation between NO metabolites and disease activity speaks in favour of the possible dual role of NO, as both immunoregulatory and pro-inflammatory molecule, in the pathogenesis of MS. [ABSTRACT FROM AUTHOR]

An abstract of the paper "Quality of life in patients with multiple sclerosis," by J. Drulovic is presented.

An abstract of the article "Sexual dysfunction in patients with multiple sclerosis," by T. Pekmezovic and colleagues, is presented.

An abstract of the article "Multiple Sclerosis Centre at the Institute of Neurology, Belgrade, Serbia," by J. Drulovic is presented.

The article analyses the role of some habits like cigarette smoking, alcohol, coffee and tea consumption, and physical activities as environmental risk factors for Multiple sclerosis in the Belgrade population using a case-control study. The study group consisted of 110 cases with clinically and/or laboratory supported MS in whom onset symptoms occurred up to 2 years prior to the interview. Statistical analysis included conditional univariate and multivariate logistic regression models.

Objectives - The increasing incidence of multiple sclerosis (MS) worldwide, especially in women, points to the crucial role of environmental and lifestyle risk factors in determining the disease occurrence. An international multicentre case-control study of Environmental Risk Factors In Multiple Sclerosis (EnvIMS) has been launched in Norway, Sweden, Italy, Serbia and Canada, aimed to examine MS environmental risk factors in a large study population and disclose reciprocal interactions. To ensure equivalent methodology in detecting age-related past exposures in individuals with and without MS across the study sites, a new questionnaire (EnvIMS-Q) is presented. Materials and methods - EnvIMS-Q builds on previously developed guidelines for epidemiological studies in MS and is a 6-page self-administered postal questionnaire. Participants are de-identified through the use of a numerical code. Its content is identical for cases and controls including 'core' and population-specific questions as proxies for vitamin D exposure (sun exposure, dietary habits and supplementation), childhood infections (including infectious mononucleosis) and cigarette smoking. Information on possible confounders or effect modifiers is also obtained. EnvIMS-Q was initially drafted in English and subsequently translated into Italian, Serbian, Norwegian, Swedish and French-Canadian. EnvIMS-Q has been tested for acceptability, feasibility and reliability. Results and Conclusions - EnvIMS-Q has shown cross-cultural feasibility, acceptability and reliability in both patients with MS and healthy subjects from all sites. EnvIMS-Q is an efficient tool to ensure proper assessment of age-specific exposure to environmental factors in large multinational population-based case-control studies of MS risk factors. [ABSTRACT FROM AUTHOR]

Objectives – To estimate the distribution of multiple sclerosis in the Belgrade population. Methods – All persons who were affected and/or died from multiple sclerosis (Poser's criteria), with residence in the Belgrade region had been collected from January 1, 1985 to December 31, 1996. Prevalence was adjusted by direct method, using world population. Results – From 1985 to 1996, 823 patients were suffering from multiple sclerosis. Sex ratio was 1:1.9. The mean age at onset was 32.2±9.8 years. A relapsing–remitting course of multiple sclerosis was reported in 50.7% patients, secondary progressive in 36.4% patients, and primary progressive in 12.9% patients. On December 31, 1996, age-adjusted prevalence of multiple sclerosis in Belgrade was 41.5/100,000, 28.2/100,000 for males, and 54.1/100,000 for females. During the period studied, statistically highly significant increasing trend of multiple sclerosis prevalence was observed (P=0.0001). Conclusions – According to findings presented in this study, Belgrade is an area with high prevalence of multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence‐based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients–Intervention–Comparator–Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score > 6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home‐based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs. [ABSTRACT FROM AUTHOR]

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS. [ABSTRACT FROM AUTHOR]

Background and purpose: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. Methods: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. Results: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre‐specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre‐specified topics, 227 (40%) on additional topics (16 guideline‐pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient‐important outcomes and of taxing issues. Conclusions: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient‐important outcomes. [ABSTRACT FROM AUTHOR]

Background: Adequate risk knowledge of patients is a prerequisite for shared decision making but few attempts have been made to develop assessment tools. Multiple Sclerosis (MS) is a chronic inflammatory disease of young adults with an increasing number of partially effective immunotherapies and therefore a paradigmatic disease to study patient involvement. Objective/methods: Based on an item bank of MS risk knowledge items and patient feedback including perceived relevance we developed a risk knowledge questionnaire for relapsing remitting (RR) MS (RIKNO 1.0) which was a primary outcome measure in a patient education trial (192 early RRMS patients). Results: Fourteen of the RIKNO 1.0 multiple-choice items were selected based on patient perceived relevance and item difficulty indices, and five on expert opinion. Mean item difficulty was 0.58, ranging from 0.14 to 0.79. Mean RIKNO 1.0 score increased after the educational intervention from 10.6 to 12.4 (p = 0.0003). Selected items were particularly difficult (e.g. those on absolute risk reductions of having a second relapse) and were answered correctly in only 30% of the patients, even after the intervention. Conclusion: Despite its high difficulty, RIKNO 1.0 is a responsive instrument to assess risk knowledge in RRMS patients participating in educational interventions. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have revealed an association between interleukin 28B (IL28B) and response to IFN-alpha treatment in hepatitis C patients. Here we investigated the influence of IL28B polymorphisms in the response to interferon-beta (IFNβ) in multiple sclerosis (MS) patients. We genotyped two SNPs of the IL28B gene (rs8099917 and rs12979860) in 588 MS patients classified into responders (n=281) and non-responders (n=307) to IFNβ. Combined analysis of the study cohorts showed no significant associations between SNPs rs8099917 and rs12979860 and the response to treatment. These findings do not support a role of IL28B polymorphisms in the response to IFNβ in MS patients. [Copyright &y& Elsevier]

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 (McDonald's 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. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of non-traumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100 000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35–64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100 000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-of-illness studies. [ABSTRACT FROM AUTHOR]

The aim of our study was to analyse clinical and paraclinical characteristics of patients with multiple sclerosis (MS) with previous diagnosis of primary-progressive (PP) MS according to the Poser's criteria and further investigate if they fulfil the McDonald's diagnostic criteria for this disorder. A total of 561 MS patients were registered in the database at the Institute of Neurology, Belgrade, from 1 January 1997 to 31 December 2000 and 63 of them (11.2%) with previous diagnosis of PPMS were analysed retrospectively. Male/female ratio was 1.3:1 and mean age at onset 33.2 years. Most frequent at onset were pyramidal (in 73% of patients) and sensory symptoms (in 41% of patients); 74.6% of patients had greater than or equal to nine brain magnetic resonance imaging (MRI) lesions. Intrathecal oligoclonal immunoglobulin G (IgG) was detected in 96.7% and prolonged visual evoked potentials (VEP) P100 latency in 82.4% of patients. Of the total study group of 561 patients, 10.2% fulfilled the recently recommended McDonald's diagnostic criteria for the diagnosis of PPMS. Our findings further support the significance of the brain/spinal cord MRI, cerebrospinal fluid and VEP findings for precise diagnostic assessment in patients with suspected PP form of MS. [ABSTRACT FROM AUTHOR]

We present a 43-year-old woman with relapsing-remitting multiple sclerosis (MS) who developed lupus syndrome after 32 months of IFN-β-1a therapy. She presented with malaise, myalgia, arthralgia and fever. Laboratory tests showed high erythrocyte sedimentation rate, anaemia and lymphopenia. Antibodies to double stranded DNA (dsDNA) of IgG, IgM and IgA classes were detected on Critidia luciliae. Additionally, high levels of anti-nucleosomal antibodies, low levels of antihistone and anti-Ro/SSA antibodies were also found. Diagnosis of drug-induced SLE was established. Treatment with IFN-β was discontinued and oral prednisone was started. Twelve weeks after cessation of IFN-β therapy, the patient's symptoms completely resolved and autoantibodies disappeared. To the best of our knowledge, this is the first report of a patient with MS in whom treatment with IFN-β induced lupus syndrome and antibodies to dsDNA and nucleosome. [ABSTRACT FROM AUTHOR]

The article discusses research on the presence of anti-AQP4 antibodies in a series of 11 Leber's hereditary optic neuropathy (LHON) patients whose diagnoses were confirmed by direct sequencing. The 11 patients had severe bilateral optic neuropathy but had no symptoms or signs of myelopathy. It suggests an association between LHON mtDNA mutations with AQP4-autoimmunity and indicates that autoimmunity could potentially modulate clinical expression in LHON mutation carriers.