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Background: The evolving therapeutic landscape requires more participation of patients with relapsing remitting multiple sclerosis (RRMS) in treatment decisions. The aim of this study was to assess the association between patient's self-perception, cognitive impairment and behavioral factors in treatment choices in a cohort of patients at an early stage of RRMS., Methods: We conducted a multicenter, non-interventional study including adult patients with a diagnosis of RRMS, a disease duration ≤18 months and receiving care at one of the 21 participating MS centers from across Spain. We used patient-reported measures to gather information on fatigue, mood, quality of life, and perception of severity of their MS. Functional metrics (Expanded Disability Status Scale [EDSS], cognitive function by the Symbol Digit Modalities Test [SDMT], 25-foot walk test) and clinical and radiological data were provided by the treating neurologist. The primary outcome of the study was status quo (SQ) bias, defined as participant's tendency to continue taking a previously selected but inferior treatment when intensification was warranted. SQ bias was assessed based on participants treatment preference in six simulated RRMS case scenarios with evidence of clinical relapses and radiological disease progression., Results: Of 189 participants who met the inclusion criteria, 188 (99.5%) fully completed the study. The mean age was 36.6 ± 9.5 years, 70.7% female, mean disease duration: 1.2 ± 0.8 years, median EDSS score: 1.0 [IQR=0.0-2.0]). Overall, 43.1% patients (n = 81/188) had an abnormal SDMT (≤49 correct answers). SQ bias was observed in at least one case scenario in 72.3% (137/188). Participant's perception of their MS severity was associated with higher SQ bias (β coeff 0.042; 95% CI 0.0074-0.076) among those with delayed cognitive processing. Higher baseline EDSS and number of T2 lesions were predictors of delayed processing speed (OR EDSS=1.57, 95% CI: 1.11-2.21, p = 0.011; OR T2 lesions=1.50, 95% CI: 1.11-2.03, p<0.01). Bayesian multilevel model accounting for clustering showed that delayed cognitive processing (exp coeff 1.06; 95% CI 1.04-1.09) and MS symptoms severity (exp coeff 1.28; 95% CI 1.22-1.33) were associated with SQ bias., Conclusion: Over 40% of patients in earlier stages of RRMS experience delays in cognitive processing that might affect their decision-making ability. Our findings suggest that patients' self-perception of disease severity combined with a delay in cognitive processing would affect treatment choices leading to status quo bias early in the course of their disease., Competing Interests: Declaration of Competing Interest G.S was supported by the Heart and Stroke Foundation of Canada Scientist Award following a peer-reviewed competition and reported receiving unrestricted grants and personal fees from Hoffman La Roche (Canada) and Roche Farma (Spain). S.S.M received payment for lecturing or travel expenses from Merck-Serono, Biogen, Sanofi-Genzyme, Roche, and Novartis. B.P.B. has received honoraria as speaker/advisor from Biogen, Sanofi and Bial. J.S. has received speaking honoraria, compensation for consulting services and support to attend scientific meetings from Almirall, Bayer, Biogen, Merck, Novartis, Sanofi, Roche and Teva. A.A. has received compensation for consulting services from Biogen, BMS, Sanofi, Roche, Janssen and Novartis; and speaking honoraria from Biogen, BMS, Sanofi, Roche, Janssen, Merck, Almirall and Novartis. A.B.C. has received courses and honoraria for her participation as speaker/meeting moderator/symposia organizer from Alter, Almirall, Bayer, Bial, Biogen, Bristol-Myers-Squibb, Lilly, Merck-Serono, Mylan, Novartis, Roche, Sanofi-Genzyme, Teva and UCB; and support to attend scientific meetings from Biogen, Bial, Merck-Serono, Novartis, Roche, Sanofi-Genzyme and Teva. J.L.S-M. has received support to attend scientific meetings from Novartis, Merck, and Biogen; speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva; and has participated in clinical trials from Biogen, Merck and Roche. F.J.B-H. has received compensation for consulting services and speaking honoraria from Almirall, Biogen, Genzyme, Merck-Serono, Novartis, Roche, Sanofi and Teva. C.C. has received compensation for consulting services, speaking honoraria and support to attend scientific meetings and courses from Merck, Teva, Sanofi-Genzyme, Novartis, Biogen, Roche, and Bristol-Myers-Squibb. L.B. has received compensation for consulting services, speaking honoraria and support to attend scientific meetings from Bayer, Celgene, Biogen, Genzyme, Merck, Novartis, Roche, Almirall and Teva. J.D.G-S. has received compensation for consulting services and speaking honoraria from Biogen, Novartis, Merck, UCB, Sanofi-Genzyme, Roche, Almirall and Teva. M.C-A. has received compensation for consulting services from Genzyme, Roche, Novartis, Sanofi and Biogen. L.NC. has received compensations from Sanofi-Genzyme, Merk, Biogen and Roche. E.A. has received speaking honoraria from Roche, Novartis, Merck, Sanofi and Biogen. M.G. has received speaking honoraria from Biogen, Sanofi, Almirall and Novartis. L.G-T. has received speaking honoraria from Biogen, Novartis, Merck, Bayer, Sanofi-Genzyme, Almirall, Roche and Teva. M.H. has participated in observational studies and has received compensation for consulting services and speaking honoraria from Roche, Merck, Sanofi, Biogen, Novartis and Bayer. J.M., R.G-B., and E.G-A. are employees of Roche Farma Spain. The rest of the authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment., Methods: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis., Results: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0-4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p=0.002)., Conclusion: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their future lives. Improving communication strategies on prognosis may help patients deal with the disease and adjust their long-term life goals. However, there is limited information on patients' preferences of long-term prognosis (LTP) communication and associated factors., Objective: The aim of this study was to describe patients' preferences and assess the factors associated with LTP communication preferences in early-stage relapsing-remitting multiple sclerosis (RRMS) patients., Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration from first attack ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The Prognosis in MS questionnaire was used to assess how much patients want to know about their LTP. Different patient-reported measures were administered to gather information on symptom severity, pain, fatigue, mood/anxiety, quality of life, stigma, illness perception, feeling of hopelessness, self-efficacy, information avoidance and coping strategies. Cognition was assessed using the Symbol Digit Modalities Test (SDMT). A multivariate logistic regression analysis was performed to assess the association between LTP information preference and demographic and clinical characteristics, as well as patients' perspectives., Results: A total of 189 patients were included (mean age: 36.1  ±  9.4 years, 71.4% female, mean disease duration: 1.2  ±  0.8 years). Median EDSS score was 1.0 (IQR = 0.0-2.0). A proportion of 68.5% (n  =  126) of patients had never discussed LTP with their neurologists, whereas 69.2% (n = 126) reported interest in knowing it (73.5% at diagnosis). Bivariate analyses suggested that patients were significantly more likely to have higher LTP information preferences if they were male and had a lower SDMT score. Male gender and a lower SDMT score were predictors of LTP information preferences., Conclusions: Patients with early-stage RRMS want to discuss their LTP shortly after diagnosis. Understanding the factors involved may be useful to design individualized communication strategies., (Copyright © 2022. Published by Elsevier B.V.)

Background: Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their autonomy and capacity to maintain employment., Objective: The aim of this study was to assess the impact on work productivity in early-stage relapsing-remitting multiple sclerosis (RRMS)., Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. Absenteeism, presenteeism, and unpaid work loss due to RRMS were measured using the Valuation of Lost Productivity (VOLP) questionnaire. The EDSS, SymptoMScreen, 5-item Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale, Symbol Digit Modalities Test, and Multiple Sclerosis Work Difficulties Questionnaire were used to gather information on disability, patients' perception of symptom severity, fatigue, mood/anxiety, cognition, and problems in the workplace, respectively. Associations between the VOLP and clinical and work outcomes were analyzed using Spearman's rank correlations., Results: A total of 189 patients were included. Mean age (SD) was 36.1 ± 9.4 years and 71.4% were female. Mean disease duration was 1.2 ± 0.8 years. Median EDSS score was 1.0 (IQR 0, 2.0). One hundred thirty patients (68.8%) were working for pay or self-employed. Fifty-three patients (40.8%) reported absence from work in the past 3 months with an average of 14.3 absent workdays. Their health problems resulted in the loss of 3.4% of their actual work time in the past 7 days. Thirty patients got help (11.8 h) with their unpaid work activities in the past 7 days. Absenteeism was significantly correlated with anxiety and depression (rho=0.298 and 0.291, p<0.001), fatigue (rho=0.214, p = 0.014), and symptom severity (rho=0.213, p = 0.015). Presenteeism was significantly correlated with fatigue (rho=0.375, p<0.001), symptom severity (rho=0.373, p<0.001), depression (rho=0.263, p = 0.008), and disability (rho=0.215, p = 0.031)., Conclusions: Productivity loss even in a RRMS population with short disease duration stresses the need for more efficient treatment control of disease activity from earlier stages., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments., Methodology: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations., Development: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: In multiple sclerosis (MS), half of affected people are unemployed within 10 years of diagnosis. The aim of this study was to assess the economic impact of MS in adult subjects with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS)., Methods: A multicenter, non-interventional, cross-sectional study was conducted. The Expanded Disability Status Scale (EDSS) and the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23) were used to assess disability and work performance, respectively. Only indirect costs were considered using the human capital method, including work costs. Professional support costs and informal caregivers' costs were also estimated., Results: A total of 199 subjects were studied (mean age: 43.9 ± 10.5 years, 60.8% female, 86.4% with RRMS). Median EDSS score was 2.0 (interquartile range: 1.0-3.5) and median MSWDQ-23 total score was 31.5 (15.2, 50.0). The number of employed subjects decreased after MS diagnosis from 70.6 to 47.2%, and the number of retired people increased (23.6%). Mean age of retirement was 43.6 ± 10.5 years. Ten percent of the population had sick leaves (absenteeism was seen in 90.9% of the student population and 30.9% of the employed population). Professional support in their daily life activities was needed in 28.1% of subjects. Costs for sick leave, work absenteeism, premature retirement and premature work disability/pensioner were €416.6 ± 2030.2, €763.4 ± 3161.8, €5810.1 ± 13,159.0 and €1816.8 ± 9630.7, respectively. Costs for professional support and informal caregiving activities were €1026.93 ± 4622.0 and €1328.72, respectively., Conclusions: MS is responsible for a substantial economic burden due to indirect and informal care costs, even in a population with low physical disability.

Background: To date, there are no available factors to predict the outcome after multiple sclerosis relapse., Aim: To investigate factors that may be useful for predicting response to methylprednisolone treatment, following a relapse of multiple sclerosis (MS)., Methods: The study included 48 MS patients enrolled in a double-blind multicenter trial to receive intravenous versus oral high-dose methylprednisolone treatment. Associations were sought between the disability status prior to relapse and the relapse severity, determined by changes in the Expanded Disability Status Scale (EDSS) score, as well as the improvements after treatment. We also analyzed the relationships between the number of magnetic resonance imaging (MRI) gadolinium-enhancing lesions (Gd+) and improvement., Results: A higher EDSS score before relapse was associated with more severe relapses (p = 0.04) and less marked improvement (odds ratio (OR) 1.8; 95% CI (1.2-2.2); p = 0.05) after methylprednisolone treatment. Relapse severity (p = 0.29) and the number of Gd+ lesions at relapse (p = 0.41) were not related with improvement., Conclusions: Clinical baseline status prior to MS relapse is a predictor of response to methylprednisolone treatment., (© The Author(s), 2015.)

Background: Recent studies show an increasing incidence of multiple sclerosis (MS) in southern Europe. Although by its geographical location and genetic characteristics Spain is expected to be similar to other southern European regions, data on incidence are scarce. The aim of this study was to determine the onset-adjusted incidence of MS in the Girona province in Catalonia (Spain)., Methods: A prospective incidence study pooling data from the population-based Catalonia MS Registry was performed. Incident cases were defined as patients who had the onset of symptoms compatible with a clinically isolated syndrome (CIS) suggestive of MS in 2009 and fulfilled McDonald-2005 criteria during follow-up. Age- and sex-specific incidence rates were obtained., Results: The Registry included 182 patients residing in Girona that presented a CIS from January 2009 to December 2013. Fifty one patients had the onset of symptoms in 2009, of whom 27 patients fulfilled the diagnostic criteria, giving an incidence of 3.6 per 100,000 (CI 95% 2.4-5.3) inhabitants; 4.3 (CI 95% 2.5-7.1) for women and 2.9 (CI 95% 1.4-5.2) for men. The age-adjusted incidence rate for the European population was 3.29 (CI 95% 3.2-3.3)., Conclusion: The incidence estimation derived in this study is consistent with recent epidemiological data of MS in southern Europe suggesting an increase in incidence in this region., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Unlabelled: Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP., Trial Registration: clinicaltrials.gov identifier: NCT00753792., (© The Author(s), 2014.)

Background: Steroids improve multiple sclerosis (MS) relapses but therapeutic window and dose, frequency and administration route remain uncertain., Objective: The objective of this paper is to compare the clinical and radiologic efficacy, tolerability and safety of intravenous methylprednisolone (ivMP) vs oral methylprednisolone (oMP), at equivalent high doses, for MS relapse., Methods: Forty-nine patients with moderate or severe relapse within the previous 15 days were randomized in a double-blind, noninferiority, multicenter trial to receive ivMP or oMP and their matching placebos. Expanded Disability Status Scale (EDSS) scores were determined at baseline and weeks 1, 4 and 12. Brain MRI were assessed at baseline and at weeks 1 and 4. Primary endpoint was a noninferiority assessment of EDSS improvement at four weeks (noninferiority margin of one point), with further key efficacy assessments of number and volume of T1 gadolinium-enhancing (Gd+), and new or enlarged T2 lesions at four weeks' post-treatment initiation. Secondary outcomes were safety and tolerability., Results: The study achieved the main outcome of noninferiority at four weeks for improved EDSS score. No differences were found between ivMP and oMP in the number of Gd+ lesions (0 (0-1) vs 0 (0-0.5), p = 0.630), volume of Gd+ lesions (0 (0-88.0) vs 0 (0-32.9) mm(3), p = 0.735), or new or enlarged T2 lesions (0 (0-194) vs 0 (0-123), p = 0.769). MP was well tolerated, and no serious adverse events were reported., Conclusions: This study provides confirmatory evidence that oMP is not inferior to ivMP in reducing EDSS, similar in MRI lesions at four weeks for MS relapses and is equally well tolerated and safe., Trial Registration: clinicaltrials.gov identifier: NCT00753792.

Background: Adherence to interferon β-1b (INFβ-1b) therapy is essential to maximize the beneficial effects of treatment in multiple sclerosis (MS). For that reason, the main objectives of this study are to assess adherence to INFβ-1b in patients suffering from MS in Spain, and to identify the factors responsible for adherence in routine clinical practice., Methodology/principal Findings: This was an observational, retrospective, cross-sectional study including 120 Spanish patients with MS under INFβ-1b treatment. Therapeutic adherence was assessed with Morisky-Green test and with the percentage of doses received. The proportion of adherent patients assessed by Morisky-Green test was 68.3%, being indicative of poor adherence. Nevertheless, the percentage of doses received, which was based on the number of injected medication, was 94.3%. The main reason for missing INFβ-1b injections was forgetting some of the administrations (64%). Therefore, interventions that diminish forgetfulness might have a positive effect in the proportion of adherent patients and in the percentage of doses received. In addition, age and comorbidities had a significant effect in the number of doses injected per month, and should be considered in the management of adherence in MS patients., Conclusion/significance: Among all the available methods for assessing adherence, the overall consumption of the intended dose has to be considered when addressing adherence.

Increasing options are dictating the development of new algorithms to provide guidance in the treatment of people with multiple sclerosis (MS). There is a wealth of evidence on the safety and efficacy of interferon-beta and glatiramer acetate, which have been used in Europe and in the United States for more than 10 years. The spectrum of approved indications for these conventional disease modifying therapies includes the treatment of relapsing-remitting MS, secondary progressive MS, and the clinically isolated syndrome. Beyond these therapies we already have the recently introduced antibody natalizumab and, in some countries, the immunosuppressive agent mitoxantrone. Oral therapies are expected in the near future, with the sphingosin-1-phosphate receptor modulator fingolimod approved in the US and the EU and the purine nucleoside analogue cladribine in Australia and Russia. The evidence on all of these conventional and novel therapeutics is reviewed in this paper to provide an overview of the changing landscape of MS treatment.

Background: Results for the e4/e2 alleles of the ApoE gene as markers of susceptibility, clinical and radiological progression, and cognitive deterioration in patients with multiple sclerosis (MS) are contradictory., Aim: The usefulness of these markers in predicting the response to interferon-β-1b (IFNβ-1b) was evaluated., Material and Methods: 95 patients with relapsing-remitting MS treated with IFNβ-1b (mean follow-up 7.44 years) were studied. We correlated the e4 and e2 alleles with the time to the first relapse or to a 1-point worsening on the Expanded Disability Status Scale, time to moderate disability, progression index, and treatment discontinuation due to inefficacy., Results: We found no association between the e4 allele and any of the variables. The e2 allele was associated with increased time to moderate disability., Conclusion: The e4 allele of ApoE has no prognostic value for the response to IFNβ-1b. The e2 allele delayed the progression of disability in our MS patient cohort., (Copyright © 2011 S. Karger AG, Basel.)

Background/aim: There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time., Methods: The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method., Results: Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found., Conclusion: Anticipation of age at onset is undetectable when adjusted for follow-up time.

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.

Multiple sclerosis (MS) is a chronic demyelinating disease, which represents a great economic burden to society. Cost-of-illness studies of MS tend to underestimate the intangible costs related to pain, anxiety and helplessness. The purpose of this study was to estimate the intangible costs of MS, and determine whether these costs increase as disability progresses. We studied 211 consecutive patients with MS who attended our MS unit. Patients mean age was 41.6 (SD: 10.7) years, 69% were female, and their mean Expanded Disability Status Scale (EDSS) score was 2.47 (SD: 2.05). Quality-of-life was measured with the EuroQoL visual analogue scale. Quality-adjusted life year (QALY) was calculated for each patient. Patients were grouped into five disability stages according to their EDSS, and QALY was compared between patients and a group of healthy controls matched by age and sex. A benchmark value was ascribed to each QALY lost, and the intangible costs per patient-year were calculated as Euros 0 (EDSS =0), Euros 1100 (EDSS =1-3), Euros 8250 (EDSS =3.5-5.5), Euros 9900 (EDSS =6-7) and Euros 11,000 (EDSS >7.5). Sensitivity analysis showed a similar progression of costs. We conclude that intangible costs are relevant in MS, especially when disability increases. Although the method to calculate the costs remains controversial, we consider that they should be included in cost analysis of MS.

Background: Multiple sclerosis (MS) is an incurable chronic disease that predominantly affects young adults. It has a high socio-economic impact which increases as disability progresses. An assessment of the real costs of MS may contribute to our knowledge of the disease and to treat it more efficiently. Our objective is to assess the direct and indirect costs of MS from a societal perspective, in patients monitored in our MS Unit (Baix Llobregat, Catalonia) and grouped according to their disability (EDSS)., Methods: We analysed data from 200 MS patients, who answered a questionnaire on resource consumption, employment and economical status. Mean age was 41.6 years, mean EDSS 2.7, 65.5% of patients were female, 79.5% had a relapsing-remitting course, and 67.5% of them were receiving immunomodulatory treatment (IT). Patients were grouped into five EDSS stages. Data from the questionnaires, hospital charts, Catalan Health Service tariffs, and figures from Catalan Institute of Statistics were used to calculate the direct and indirect costs. The cost-of-illness method, and the human capital approach for indirect costs, were applied. Sensitivity analyses were performed to strengthen results., Results: The mean total annual cost of MS per patient results 24,272 euros. This cost varied according to EDSS: 14,327 euros (EDSS = 0), 18,837 euros (EDSS = 1-3), 27,870 euros (EDSS = 3.5-5.5), 41,198 euros (EDSS = 6-7) and 52,841 euros (EDSS>7.5). When the mean total annual costs was adjusted by the mean % of patients on IT in our Unit (31%) the result was 19589 euros. The key-drivers for direct costs were IT in low EDSS stages, and caregiver costs in high stages. Indirect costs were assessed in terms of the loss of productivity when patients stop working. Direct costs accounted for around 60% of total costs in all EDSS groups. IT accounts from 78% to 11% of direct costs, and decreased as disability progressed., Conclusion: The total mean social costs of MS in a cohort from Baix Llobregat (Catalonia) were estimated at 24,272 euros per patient/year, and ranged between 14,327 euros (EDSS = 0) and 52,841 euros (EDSS = 7.5-9.5). Total costs, and particularly informal and direct costs, increased as the disability progressed. IT should be able to delay the progression of disability to be efficient and not only effective.

Introduction: The objective of this study is to calculate direct, indirect and intangible costs of a relapse in multiple sclerosis (MS) in our cohort of patients., Methods: Data from patient questionnaires, hospital charts, Catalan Public Healthcare System tariffs and Catalan Statistics Institute. We employed a cost-of-illness method. The human capital approach was used to estimate indirect costs, and quality-of-life measurements were used to estimate intangible costs., Results: 148 MS patients monitored in our MS-Unit consecutively answered the questionnaire elaborated. We calculated 1,498.5-1,537.9 euros for direct costs (hospital admission and outpatient, respectively) and 1,530.6 euros for indirect costs. We estimated an average total cost of 3,048.8 euros per patient/relapse. We also calculated intangible costs, 539 euros per patient and relapse, which should be added to the previous figure., Conclusions: The total cost of a MS relapse in our population (3,048.8 euros) is lower than the cost reported in the literature. The economic impact of MS is due to its disabling progression rather than to relapses

Julia Sabin,1 Elisa Salas,2 Jesús Martín-Martínez,3 Antonio Candeliere-Merlicco,4 Francisco Javier Barrero Hernández,5 Ana María Alonso Torres,6 José Luis Sánchez-Menoyo,7 Laura Borrega,8 María Rodríguez-Rodríguez,9 Montserrat Gómez-Gutiérrez,10 Sara Eichau,11 Miguel Ángel Hernández-Pérez,12 Carmen Calles,13 Eva Fernandez-Diaz,14 Olga Carmona,15 Aida Orviz,16 Ana López-Real,17 Pablo López-Muñoz,18 Amelia Mendoza Rodríguez,19 Eduardo Aguera-Morales,20 Jorge Maurino2 1Department of Neurology, Hospital Universitario Puerta de Hierro, Madrid, Spain; 2Medical Department, Roche Farma, Madrid, Spain; 3Department of Neurology, Hospital Universitario Miguel Servet, Zaragoza, Spain; 4Department of Neurology, Hospital Rafael Méndez, Lorca, Spain; 5Department of Neurology, Hospital Clínico Universitario San Cecilio, Granada, Spain; 6Department of Neurology, Hospital Regional Universitario de Málaga, Málaga, Spain; 7Department of Neurology, Hospital de Galdakao-Usansolo, Galdakao, Spain; 8Department of Neurology, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain; 9Department of Neurology, Hospital Universitario Lucus Augusti, Lugo, Spain; 10Department of Neurology, Hospital San Pedro de Alcántara, Cáceres, Spain; 11Department of Neurology, Hospital Universitario Virgen Macarena, Sevilla, Spain; 12Department of Neurology, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain; 13Department of Neurology, Hospital Universitario Son Espases, Palma de Mallorca, Spain; 14Department of Neurology, Hospital Universitario de Albacete, Albacete, Spain; 15Department of Neurology, Fundació Salut Empordà, Figueres, Spain; 16Department of Neurology, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; 17Department of Neurology, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain; 18Department of Neurology, Hospital Arnau de Vilanova, Llíria, Spain; 19Department of Neurology, Complejo Asistencial de Segovia, Segovia, Spain; 20Department of Neurology, Hospital Universitario Reina Sofía, Córdoba, SpainCorrespondence: Jorge Maurino, Ribera del Loira 50, Madrid, 28042, Spain, Tel + 34 913 24 81 00, Email jorge.maurino@roche.comPurpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients’ decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS).Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted.Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0– 7.0) years. Median EDSS score was 1.0 (0– 2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis.Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.Keywords: multiple sclerosis, disease-modifying therapies, decision-making, decisional conflict, disease-related knowledge, self-management

Jose M García-Domínguez,1 María L Martínez-Ginés,1 Olga Carmona,2 Ana B Caminero,3 Daniel Prefasi,4 Jorge Maurino,4 Javier Ballesteros5 On behalf of the W-IMPACT Clinical Investigators 1Department of Neurology, Hospital Universitario Gregorio Marañón, Madrid, Spain; 2Department of Neurology, Hospital de Figueres, Figueres, Spain; 3Department of Neurology, Hospital Nuestra Señora de Sonsoles, Complejo Asistencial de Ávila, Ávila, Spain; 4Medical Department, Roche Farma, Madrid, Spain; 5Department of Neurosciences and CIBERSAM, Universidad del País Vasco, Leioa, Spain Background: Understanding caregiver strain may be crucial to determine which interventions are most needed to mitigate the negative impact of caring for people with multiple sclerosis (MS). The Caregiver Strain Index (CSI) is a brief self-assessment tool for measuring the caregivers’ perceived level of burden. Limited information is available on the psychometric performance of the CSI in MS.Objective: The objective of this study was to assess the factor structure and construct validity of the CSI in MS.Methods: A multicenter, cross-sectional study in adults with relapsing-remitting and primary-progressive MS (McDonald 2010 criteria) was conducted. A non-parametric item response theory (IRT) procedure, Mokken analysis, was conducted to assess the dimensional structure of the CSI. A parametric IRT model for dichotomous responses, Rasch model, was conducted to assess item characteristics. Discriminative validity was assessed comparing the distribution of its overall score between people with mild and moderate-severe disability according to the Expanded Disability Status Scale.Results: A total of 72 MS caregivers were studied. The prevalence of a high level of strain was 23.6% (n=17). Internal reliability was high (Cronbach’s alpha =0.91). According to Mokken analysis, CSI represented a unidimensional construct of caregiver burden although two of the total 13 items (#1 and #13) could not be assigned to any factor by an automatic item selection procedure. Without these items, the scalability moved from a weak (Hi =0.37) to a medium scale (Hi =0.44). However, the item characteristic curve of the Rasch model showed a range of appropriate difficulty and the item and person parameters showed good fit (Andersen likelihood ratio test =18.40, df =11; P-value =0.07; all item values for the infit). The CSI score showed a good discriminative validity between the levels of disability of the care recipient.Conclusion: The CSI questionnaire shows appropriate psychometric characteristics being a useful instrument to assess different aspects of burden in MS caregivers in clinical practice. Keywords: caregivers, multiple sclerosis, psychometrics, caregiver burden, strain

Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP.Trial registration: clinicaltrials.gov identifier: NCT00753792 [ABSTRACT FROM AUTHOR]

The article focuses on the study which compares the clinical and radiologic efficacy of intravenous methylprednisolone (ivMP) against oral methylprednisolone (oMP) at equivalent high doses for multiple sclerosis (MS) relapse. It states the main outcome of noninferiority at four weeks for improved expanded disability status scale (EDSS) score. It mentions that oMP is not inferior to ivMP in reducing the score of EDSS.

Carmona O, Masuet C, Santiago O, Alía P, Moral E, Alonso-Magdalena L, Casado V, Arbizu T. Multiple sclerosis and cognitive decline: is ApoE-4 a surrogate marker? Acta Neurol Scand: 2011: 124: 258-263. © 2011 John Wiley & Sons A/S. Background - The role of the apolipoprotein E (ApoE) polymorphism has been well demonstrated in neurodegenerative disorders such as Alzheimer. However, its role in multiple sclerosis (MS) remains unclear. Aims - The aims of our study were as follows: (i) to assess whether ApoE-4 might be a surrogate marker of cognitive decline in MS; (ii) to confirm the presence of cognitive impairment in mildly disabled patients treated with interferon-beta; and (iii) to analyse the correlation between cognitive disturbances and clinical variables. Material and methods - Fifty relapsing-remitting MS patients underwent a battery of neuropsychological tests and were genotyped for ApoE. Their scores were compared with those of 35 controls. Results - No association was found between ApoE-4 and cognitive impairment. Significant differences in most domains were observed between MS and the control group. Cognitive decline was not related to disability progression. Conclusion - No association between cognitive impairment and ApoE-4 or clinical markers was detected in our MS patients. [ABSTRACT FROM AUTHOR]

Abstract: Various studies have reported deficits in frontal cognitive functions in patients with multiple sclerosis (MS). However, the frontal deficit is not uniform and is often very subtle. The aim of this study was to assess frontal functions in a broad sample of patients with relapsing–remitting multiple sclerosis at the mild-to-moderate stage. The sample included a series of 165 patients. We used a test battery covering the frontal functions that have been described as being altered in MS. Significant differences were found between the patient group and healthy controls on the WAIS Arithmetic subtest, the PASAT, category word recall and the number of trials required to reach the first category of the WCST. In conclusion, we observed significant differences with respect to the control group in terms of information processing speed and working memory. These functions involve connections between the frontal lobe and other brain regions. [Copyright &y& Elsevier]

In order to ensure sufficient disease activity, patients with relapsing remitting (RR) multiple sclerosis (MS) are often included in randomized placebo-controlled trials, only if they have a high baseline activity. These patients, whose evolution is unusual in the pre-study period, will tend to show a more usual behavior when followed up over a period of time. This phenomenon is known as regression to the mean. Regression to the mean should be taken into account in correctly interpreting long-term studies of cohorts treated without a placebo control group, which use the baseline period as control. The aim of this study was to evaluate the relevance of this phenomenon in a non-treated cohort of RRMS patients, selected with similar criteria to those used in randomized placebo-controlled clinical trials. Forty-four patients with definite RRMS, with two or more relapses in the previous two years, and a baseline EDSS ≤5.5 were prospectively followed. The mean number of relapses spontaneously decreased from 1.72 (SD: 1.4) in the year prior to enrolment, to 1.0 (SD: 1.3) during the first year of follow-up (P < 0.05). Regression to the mean may explain as much as 40% of the reduction in the relapse rate from the baseline period to the period on-study. [ABSTRACT FROM AUTHOR]