IntroductionEffective treatments that reduce relapses can diminish the impact on MS costs in the long-term. This study aims to estimate direct costs of RRMS relapses in Catalonia (Spanish region).MethodsMulti-centre, prospective, cross-sectional observational study with retrospective data collection. Estimated costs: disease-modifying therapies (DMTs) and symptoms treatments, use of hospital and ambulatory resources, technical aids, transport and paid caregivers from the National Health System (NHS) and global perspectives.ResultsOne hundered and forty (140) suitable patients were included to estimate direct costs (mean [SD] age: 40.7 [10] years; females: 71.5%; low EDSS score at relapse start: 77.5%). Mean total direct costs of relapse/patient were €4,541 (NHS) and €4,626 (global). A subanalysis was performed in patients with relapses lasting ≤90 days (100 patients), relapse total direct costs/patient were €4,989 (NHS) and €5,115 (global). Motor relapses presented a higher cost (a mean of €9,345/patient). Mean total direct cost/patient was higher when there was a DMT switch due to the relapse (€14,370 compared to €1,149), from a global perspective.ConclusionMean direct costs of RRMS relapse/patient in Catalonia were €4,989 and €5,115 for NHS and global perspectives, respectively. The type of relapse and switching the DMT due to the relapse were associated with an increase in direct costs.

Background and purposeCytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early‐life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non‐early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses.MethodsMulticentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein–Barr virus and human herpesvirus‐6, as well as T‐cell and natural killer (NK)‐cell immunophenotypes.ResultsCytomegalovirus seroprevalence in early MS was lower than in non‐early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T‐cells (CD27−CD28−, CD57+, LILRB1+) and NKG2C+ NK‐cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age‐related decline in serum anti‐EBNA‐1 antibodies (P < 0.01), but no CMV‐related differences in anti‐human herpesvirus‐6 humoral responses.ConclusionsLow CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T‐cell and NK‐cell subsets and/or modulation of Epstein–Barr virus‐specific immune responses at early stages of the disease.

Introduction: Although subcutaneous treatments for multiple sclerosis (MS) have been shown to be effective, adverse reactions and pain may adversely affect treatment satisfaction and adherence. This study presents an adapted and validated Spanish version of the Multiple Sclerosis Treatment Concerns Questionnaire (c) (MSTCQ), which evaluates satisfaction with the injection device (ID) across 4 domains: injection system (A), side effects (B) (flu-like symptoms, reactions, and satisfaction), experience with treatment (C) and benefits (D). Methods: Two study phases: 1) Cultural adaptation process with input from experts (n = 6) and patients (n = 30). 2) Validation obtained by means of an observational, cross-sectional, multi centre study evaluating 143 adult MS patients using an ID. Tools employed: MSTCQ, Patient Reported Indices for Multiple Sclerosis (PRIMUS<((C))under bar>), and Treatment Satisfaction Questionnaire for Medication (TSQM (c)). Psychometric properties: Feasibility (percentage of valid cases and floor/ceiling effects); Reliability (Cronbach alpha) and test-retest correlation (n =41, intractass correlation coefficient, ICC); and construct validity (factor analysis of domains A and B) and convergent validity (Spearman rank-order correlation for MSTCQ (c) vs TSQM (c)). Results: Mean age (SD) was 41.94 (10.47) years, 63% of the group were women, and 88.11% presented relapsing-remitting MS. Mean (SD) EDSS score was 2.68 (1.82) points. MSTCQ (c) completion was high (0%-2.80% missing data). Internal consistency was high at alpha = 0.89 for the total score (A+ B) and alpha = 0.76, 0.89, and 0.92 for domains A, B, and C, respectively. The version demonstrated excellent test-retest reliability for the total (ICC = 0.98) and for domains A, B, and C: ICC =0.82, 0.97, and 0.89, respectively. Factor analysis corroborated the internal structure of the original questionnaire. The association between total and domain scores on both the MSTCQ (c) and the TSQM (c) was moderately strong (Rho = 0.42-0.74) and significant (P <.05 and P<.01). Conclusion: The Spanish version of MSTCQ demonstrates appropriate psychometric properties. 2014 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U.

Background: Human cytomegalovirus (HCMV) causes a highly prevalent infection which may have a multifaceted impact on chronic inflammatory disorders. However, its potential influence in multiple sclerosis (MS) remains controversial. The HCMV-host interaction may induce an adaptive reconfiguration of the natural killer (NK) cell compartment, whose hallmark is a persistent expansion of peripheral NKG2C+ NK-cells.Objective: The purpose of this study was to evaluate whether the HCMV-driven NKG2C+ NK-cell expansion is related to the MS clinical course.Methods: Multicentre analysis of NKG2C expression and genotype according to HCMV serostatus and time of assignment of irreversible disability scores in 246 MS patients prospectively followed up in our institutions.Results: NKG2C expression was unrelated to disease-modifying drugs, remained stable under steady-state conditions, and was higher in HCMV(+) NKG2C(+/+) homozygous individuals. NKG2C+ NK-cell expansion in HCMV(+) patients, as compared to HCMV(+) or HCMV(-) patients with lower NKG2C+ NK-cells proportions, conferred a lower risk of progression in Cox regression analysis (Expanded Disability Status Scale (EDSS)>3.0, hazard ratio (HR)=0.33, 95% confidence interval (CI) 0.15-0.71, p=0.005; EDSS>5.5, HR=0.23, 95% CI 0.07-0.74, p=0.014). Neither HCMV serostatus nor NKG2C genotype appeared to be related to disability progression.Conclusions: HCMV may exert a beneficial influence on MS, decreasing the risk of disability progression in those patients displaying a virus-driven NKG2C+ NK-cell expansion.

OBJECTIVE- to conduct a cultural adaptation and test the psychometric properties of the MSTCQ© ("MS Treatment Concerns Questionnaire") Spanish language version. This tool evaluates atisfaction with the injection device (DI) for the treatment of Multiple Sclerosis (MS) in 4 dimensions: Injection system(A), Side-effects(B) (flu-like symptoms, reactions, and satisfaction), Treatment experience(C) and Benefits(D). BACKGROUND- Albeit effectiveness of injected treatments for MS, adverse reactions and pain may involve continuity and Satisfaction problems. We carried out this study in order to meet the need for specific instruments in measuring patient satisfaction with treatment MS in spanish language. DESIGN/METHODS-Two stages: 1)Cultural adaptation: Forward-backward translation, translation panels, and expert (n=6) and patient (n=27) panels; 2)Validation: Observational, cross-sectional, multicenter study, 7-month long study. Adult patients suffering from MS and using an injection device were evaluated in a single visit (n=143). Questionnaires: MSTCQ©, Patient-Reported Indices for MS (PRIMUS©), Treatment Satisfaction Questionnaire for Medication(TSQM©). Psychometric properties: Feasibility (% valid cases and ground/ceiling effects); Reliability (Cronbach α) and test-retest (41 patients, Intraclass Correlation Coefficient, ICC); as well as construct (Factorial analysis of dimensions A and B, FA) and convergent (Spearman MSTCQ vs. TSQM) validity. RESULTS- Mean age(SD) in cases was 41.94(10.47) years, 63% female, 88.11% suffering from Relapsing-Remitting MS, EDSS mean(SD) was 2.68(1.82). MSTCQ feasibility was adequate (missing 0%-2.80%). High internal consistency, total score (A+B) α =0.89, by dimensions α (A, B and C): 0.76, 0.89 and 0.92, respectively. Very good accordance was found between total (ICC= 0.98) and by dimensions ICC (A, B and C) scores: 0.82, 0.97 and 0.89, respectively. The FA confirms dimensions A and B from the original questionnaire. Lastly, the association between total and by dimensions scores, from MSTCQ and TSQM was,overall, moderately strong (Rho 0.74-0.42) and significant (p<0.05; p<0.01). CONCLUSIONS-The Spanish version of the MSTCQ questionnaire observes adequate psychometric properties (feasibility, reliability, construct and criterion validity). Supported by: Novartis España

Introduction: Progressive multifocal leukoencephalopathy (PML) is caused by the JC polyomavirus, which occurs in immunocompromised patients, HIV or patients under immunosuppressant /INS;treatment (natalizumab, rituximab …/INS;), associated with a poor prognosis. Few cases of PML on immunocompetent patients have been reported.

CD56(bright) NK cells, which may play a role in immunoregulation, are expanded in multiple sclerosis (MS) patients treated with immunomodulatory therapies such as daclizumab and interferon-beta (IFNβ). Yet, whether this NK cell subset is directly involved in the therapeutic effect is unknown. As NK receptor (NKR) expression by subsets of NK cells and CD8+ T lymphocytes is related to MS clinical course, we addressed whether CD56(bright) NK cells and NKR in IFNβ-treated MS patients differ according to the clinical response. IFNβ was associated to lower LILRB1+ and KIR+NK cells, and higher NKG2A+NK cell proportions, an immunophenotypic pattern mainly found in responders. After IFNβ treatment, a CD56(bright) NK cell expansion was significantly related to a positive clinical response. Our results reveal that IFNβ may promote in responders changes in the NK cell immunophenotype, corresponding to the profile found at early maturation stages of this lymphocyte lineage.

INTRODUCTION:The first epidemiological studies on multiple sclerosis (MS) around the world pictured a north to south latitudinal gradient that led to the first genetic and environmental pathogenic hypothesis. MS incidence seems to be increasing during the past 20 years based on recent data from prospective studies performed in Europe, America and Asia. This phenomenon could be explained by a better case ascertainment as well as a change in causal factors. The few prospective studies in our area together with the increase in the disease in other regions, justifies an epidemiological MS project in order to describe the incidence and temporal trends of MS.DEVELOPMENT:A prospective multicenter MS registry has been established according to the actual requirements of an epidemiological surveillance system. Case definition is based on the fulfillment of the McDonald diagnostic criteria. The registry setting is the geographical area of Cataluna (northeastern Spain), using a wide network of hospitals specialized in MS management.CONCLUSION:Recent epidemiological studies have described an increase in MS incidence. In order to contrast this finding in our area, we consider appropriate to set up a population based registry.