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Objective: To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods: An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results: Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions: The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance. [ABSTRACT FROM AUTHOR]

Background: While there is much research that focuses on the association between cold spell and their impacts on daily mortality at the city level, we analyze the impact related to social context and demographic variables at levels lower than the municipal. Methods: The objective of this study was to determine the role of the percentage of people over age 65, income level and percentage of homes without heating in the analysis of the impact of cold waves on daily mortality between January 1, 2010 and December 31, 2013 in different districts of the municipality of Madrid. We calculated Relative Risks (RR) and Attributable Risks (RA) for each of 17 districts to determine correlations between the effect of cold waves and daily mortality due to natural causes (CIEX: A00-R99) using Generalized Linear Models (GLM) of the Poisson family (link log). The pattern of risks obtained by district was analyzed using binomial family models (link logit), considering socioeconomic and demographic variables. Results: In terms of results, an impact of cold on mortality was detected in 9 of the 17 districts analyzed. The analysis of risk patterns revealed that the probability of detecting an impact in a district increases in a statistically significant way (p-value <0.05) with a higher percentage of homes without heating systems and a higher percentage of population over age 65. Conclusions: The results obtained identify the factors that should be considered in public health policies that target the district level to reduce the impact of cold waves. Key messages: • Ageing and the absence of heating systems are key variables which explain vulnerability to cold spell. • Cold spell related mortality risks can be reduced by applying prevention health public plans. [ABSTRACT FROM AUTHOR]

Natalizumab has been shown to be effective in pivotal clinical trials in multiple sclerosis; however, the patients in whom treatment is indicated in clinical practice have a different clinical profile from those included in the clinical trials. The aim of this study is therefore to collect data on natalizumab use in everyday clinical practice in Spain. The 86 participating centers throughout Spain submitted data on disease characteristics at baseline and after treatment. Valid data were available for 1,364 patients (69.3% women, 86.9% with relapsing-remitting disease). Ninety-three percent had received prior therapy for multiple sclerosis. For the 825 patients on treatment for at least a year, the annualized relapse rate (ARR) decreased from median 2.0 [mean 2.01, 95% confidence interval (CI) 1.92-2.11] in the year prior to natalizumab to 0.0 (mean 0.25, 95% CI 0.21-0.29) at 1 year ( p < 0.001). The Expanded Disability Status Scale (EDSS) score decreased from median 3.5 at baseline (mean 3.71, 95% CI 3.60-3.82) to 3.0 (mean 3.37, 95% CI 3.25-3.49) ( p < 0.0001). The discontinuation rate was 14%. One patient discontinued natalizumab due to progressive multifocal leukoencephalopathy (PML) and another due to probable PML (subsequently confirmed). Although our patients had more severe disease than those in the pivotal study, a similar reduction in ARR was observed. This finding is in line with previous observational studies. The effect was independent of baseline EDSS. [ABSTRACT FROM AUTHOR]

Background: Although there is significant scientific evidence on the impact of heat waves, there are few studies that analyze the effects of sociodemographic factors on the impact of heat waves below the municipal level. Methods: The objective of this study was to analyze the role of income level, percent of the population over age 65, existence of air conditioning units and hectares (Ha) of green zones in districts in Madrid, in the impact of heat on daily mortality between January 1, 2010 and December 31, 2013. Seventeen districts were analyzed, and Generalized Linear (GLM) Poisson Regression Models were used to calculate relative risks (RR) and attributable risks (RA) for the impact of heat waves on mortality due to natural causes (CIEX:A00-R99). The pattern of risks obtained was analyzed using GLM univariates and multivariates of the binomial family (link logit), introducing the socioeconomic and demographic variables mentioned above. Results: The results indicate that heat wave had an impact in only three of the districts analyzed. In the univariate models, all of the variables were statistically significant, but Ha of green zones lost significance in the multivariate model. Income level, existence of air conditioning units, and percent of the population over age 65 in the district remained as variables that modulate the impact of heat wave on daily mortality in the municipality of Madrid. Income level was the key variable that explained this behavior. Conclusions: The results obtained in this study show that there are factors below the municipal level (district level) that should be considered as focus areas for health policy in order to decrease the impact of heat and promote the process of adaptation to heat in the context of climate change. Key messages: • There are factors below the municipal level which should be considered for health policy in order to decrease health heat impacts. • Privation hamper isolation of ageing people from extreme outdoor temperatures. Therefore, in some cases poverty could become the key risk factor that explain the vulnerability to heat waves. [ABSTRACT FROM AUTHOR]

to assess the Heat (HW) and Cold Waves (CW) risks on health in the urban municipality of Getafe. time series analysis between 01/01/1999–31/10/2013. Dependent variable: daily mortality due to natural causes – (ICD-10): A99-R99–. Independent variables: the maximum (T max) and minimum (T min) daily temperature. The mortality-temperature relationship was analysed to determine the thresholds of HW (Threshold heat) and CW (Threshold cold). Using Poisson GLM (link = log), the Relative Risk (RR), Attributable Risk (AR) and Attributable Mortality (AM) were determined for each degree of the T max exceeding the Threshold heat (T heat) and for each degree of T min under the Threshold cold (T cold). Finally, socioeconomic variables were analysed descriptively. Threshold heat was 36 °C while Threshold cold was 0 °C. The RRs associated with T heat , i.e. 1.08 (1.03 1.14), are akin to those obtained for T cold, i.e. 1.05 (1.03 1.08). There were 202 HW and 430 CW episodes. The AM to HW totalled 61 (25, 96) deaths, while that attributable to CW reached 146 (82,211) deaths. The vulnerability in Getafe seems to be lower than in surrounding similar urban and rural cities. The singular urban development of the municipality may have granted it an advantage over surrounding municipalities regarding temperature extremes. • Getafe is vulnerable to heat and cold waves. • Their singular urban planning may give it a relative advantage but further research is needed. • Health Plans for cold waves should be locally adjusted. [ABSTRACT FROM AUTHOR]

Background: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population., Methods: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected., Results: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs., Conclusions: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children., Methods: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure., Results: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100])., Discussion: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks., Classification of Evidence: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Introduction: SARS-CoV-2 variants are defined by specific genome-wide mutations compared to the Wuhan genome. However, non-clade-defining mutations may also impact protein structure and function, potentially leading to reduced vaccine effectiveness. Our objective is to identify mutations across the entire viral genome rather than focus on individual mutations that may be associated with vaccine failure and to examine the physicochemical properties of the resulting amino acid changes., Materials and Methods: Whole-genome consensus sequences of SARS-CoV-2 from COVID-19 patients were retrieved from the GISAID database. Analysis focused on Dataset&#95;1 (7,154 genomes from Italy) and Dataset&#95;2 (8,819 sequences from Spain). Bioinformatic tools identified amino acid changes resulting from codon mutations with frequencies of 10% or higher, and sequences were organized into sets based on identical amino acid combinations., Results: Non-defining mutations in SARS-CoV-2 genomes belonging to clades 21 L (Omicron), 22B/22E (Omicron), 22F/23A (Omicron) and 21J (Delta) were associated with vaccine failure. Four sets of sequences from Dataset&#95;1 were significantly linked to low vaccine coverage: one from clade 21L with mutations L3201F (ORF1a), A27- (S) and G30- (N); two sets shared by clades 22B and 22E with changes A27- (S), I68- (S), R346T (S) and G30- (N); and one set shared by clades 22F and 23A containing changes A27- (S), F486P (S) and G30- (N). Booster doses showed a slight improvement in protection against Omicron clades. Regarding 21J (Delta) two sets of sequences from Dataset&#95;2 exhibited the combination of non-clade mutations P2046L (ORF1a), P2287S (ORF1a), L829I (ORF1b), T95I (S), Y145H (S), R158- (S) and Q9L (N), that was associated with vaccine failure., Discussion: Vaccine coverage associations appear to be influenced by the mutations harbored by marketed vaccines. An analysis of the physicochemical properties of amino acid revealed that primarily hydrophobic and polar amino acid substitutions occurred. Our results suggest that non-defining mutations across the proteome of SARS-CoV-2 variants could affect the extent of protection of the COVID-19 vaccine. In addition, alteration of the physicochemical characteristics of viral amino acids could potentially disrupt protein structure or function or both., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ulzurrun, Grande-Pérez, del Hoyo, Guevara, Gil, Sorzano and Campillo.)

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis., Objective: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain., Development: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group., Conclusion: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice., (Copyright © 2019 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments., Methods: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome., Results: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome., Conclusions: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population., Objective: To evaluate DMF tolerability, safety and persistence in MS in a real-world setting., Methods: We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect data on most frequent adverse events (AE). Regression models were used to analyze the effect of demographic and clinical characteristics on risk of AEs and DMF discontinuation., Results: We collected data of 886 patients (2681 patients/years-exposition) with median 39.5 (IQR 23, 51.5) months on DMF exposure; 25.3% were treatment naïve and 74.7% switched to DMF from other disease-modifying therapies. DMF was discontinued in 29.9% of patients, in 13.2% due to AEs and in 13.5% to inefficacy. AEs were experienced by 71.2%, being flushing the most frequent (44.1%), 5.4% developed grade III lymphopenia, without cases of grade IV. Females showed a higher risk of flushing and gastroenteric symptoms (OR 1.49, p = 0.011; OR 1.69, p = 0.001, respectively); lymphopenia was associated with older age (OR 1.04, p < 0.001), and a higher EDSS with lymphopenia (OR 1.10, p = 0.035) and DMF withdrawal (HR 1.43, p = 0.012). No safety problems were reported., Conclusions: Our findings confirm good tolerability and safety of DMF in real-world setting and suggest that women have an increased risk of AEs and higher baseline disability involves greater risk of drug discontinuation.

Purpose: The objective of this study was to characterize the demographic and clinical profile of RRMS patients receiving fingolimod in Spain, and to evaluate drug effectiveness and safety in clinical practice., Methods: This observational, retrospective, multicentre, nationwide study was performed at 56 Spanish hospitals and involved 804 RRMS patients who received oral fingolimod (0.5 mg) since November 2011, with a minimum follow-up of 12 months., Results: The mean annualized relapse rate (ARR) in the year before fingolimod was 1.08 and the median EDSS was 3; patients were exposed to fingolimod for 2.2 years as average; regarding magnetic resonance imaging (MRI) activity, more than half of the patients had >20 lesions at baseline. Patients were previously treated with first-line injectable DMTs (60.3%), or natalizumab (31.3%), and 8.3% were naïve patients. Overall, the ARR significantly decreased to 0.28, 0.22 and 0.17 (74.1%, 79.7% and 83.5% of relative reduction, respectively) after 12, 24 and 36 months of treatment, P<0.001. The ARR of patients who switched from natalizumab to fingolimod was stable over the study. Most of the patients (88.7%) were free from confirmed disability and MRI activity (67.3%) after 24 months. The persistence after 12 months on fingolimod was 93.9%., Conclusions: The subgroups of patients analysed showed differential baseline demographic and clinical characteristics. The analysis of patients who received fingolimod in routine clinical practice confirmed adequate efficacy and safety, even for long-term treatment. The present data also confirmed the positive benefit/risk balance with fingolimod in real-world clinical practice setting., Competing Interests: Authors have read the journal's policy and the authors of this manuscript have the following competing interests: - Francisco Barrero has received consulting or speaking fees from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Roche, Sanofi and Teva. Francisco Barrero discloses no conflict of interest in the elaboration of this paper. - Javier Mallada-Frechin has received consulting or speaking fees from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Roche, Sanofi and Teva. Javier Mallada-Frechin discloses no conflict of interest in the elaboration of this paper. - Maria Luisa Martínez-Ginés discloses no conflict of interest. - María Eugenia Marzo discloses no conflict of interest. - Virginia Meca-Lallana has received consulting or speaking fees from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Roche, Terumo, Sanofi and Teva. Virginia Meca-Lallana discloses no conflict of interest in the elaboration of this paper. Response to Reviewers - Guillermo Izquierdo has received consulting or speaking fees from Actelion, Almirall, Bayer, Biogen-Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi and Teva; and research support from Almirall, Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi and Teva. Guillermo Izquierdo discloses no conflict of interest in the elaboration of this paper. - José Ramón Ara has received consulting honoraria from Genzyme, Novartis and Sanofi; and honoraria for lecturing or travel expenses for attending meetings from Biogen Idec, Genzyme, Novartis and Sanofi-Aventis. José Ramón Ara discloses no conflict of interest in the elaboration of this paper. - Celia Oreja-Guevara has received consulting or speaking fees from Actelion, Biogen, Merck Serono, Genzyme, Novartis, Roche, Sanofi, Teva, and Novartis. Celia Oreja-Guevara discloses no conflict of interest in the elaboration of this paper. - José Meca-Lallana has received consulting or speaking fees from Biogen, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. José Meca-Lallana discloses no conflict of interest in the elaboration of this paper. - Lucía Forero has received consulting or speaking fees from Biogen, Merck Serono, Novartis, Roche and Sanofi. Lucía Forero discloses no conflict of interest in the elaboration of this paper. - ISV and MJM are employed by Novartis Farmacéutica, S.A. There are no patents, products in development or marketed products to declare. The ISV and MJM’s commercial affiliation do not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Treatment of multiple sclerosis is based on the administration of the disease modifying drugs (DMD), used to slow the natural course of the disease., Aim: To assess the degree of compliance of Spanish neurologists with 2010 Spanish Neurology Society (SEN) treatment guidelines., Patients and Methods: Observational, retrospective and multicenter study of 218 adult patients with at least five years of disease evolution and under treatment with DMD. Data on their past/current management was obtained from their medical records and descriptively compared to SEN recommendations., Results: According to SEN 2010 guidelines, 82% of patients had an adequate clinical response and 18% had an inadequate clinical response to their current DMD; 94% and 92%, respectively, maintained that treatment. Patients in which inadequate clinical response did not motivate a change in the current DMD more frequently had higher disability decline and higher number of relapses during previous treatments, and longer treatment duration with their current DMD. Regarding the sequence of DMDs used, 48% of patients initiated first-line treatment with interferon beta-1a administered through subcutaneous (29%) or intramuscular injections (19%), followed by interferon beta-1b, and glatiramer acetate. Some patients received second-line treatments as second/third option (15% and 28% respectively), but these treatments (mostly natalizumab) were only widespread from fourth treatment onwards., Conclusions: In accordance with SEN 2010 guidelines, the majority of patients from the study had an adequate clinical response. A high percentage of patients with an inadequate clinical response remained with their current treatment. An explanation to this phenomenon could be found in the chronic, complex and variable nature of multiple sclerosis.

Introduction: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab., Material and Methods: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed., Results and Conclusions: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient., (Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: This study outlines the design of an electronic register of patients with multiple sclerosis who began treatment with fingolimod in Spain. The system is intended to serve as a tool to monitor its utilisation in daily clinical practice and thus allow optimisation of the way it is used., Aims: To establish the profile of patients with multiple sclerosis undergoing treatment with fingolimod and to determine the effectiveness and safety of this treatment in daily clinical practice., Development: An observation-based, retrospective and prospective, multi-centre registry is set up, which will be active for five years. Forty neurologists working in Spain will participate in the project. Patients treated with fingolimod who fulfil the selection criteria will be included in the study. The effectiveness variables that will be evaluated are: disability measured by means of the Expanded Disability Status Scale, the rate of attacks, T1 gadolinium-enhancing lesions and new lesions in T2, and the percentage of patients who were free of activity and those who require concomitant treatments. The tolerability variables that will be evaluated are: the rate of patients who present events and adverse reactions, respectively, with a separate analysis of those presenting after the first dose or that are related to the fingolimod risk management plan and the treatment dropout rate., Conclusions: New pharmaceuticals that have only recently been commercialised require more information about their effectiveness and safety, beyond the controlled environment of a clinical trial. Initiatives involving electronic registries such as the Gilenya register are a solution that can respond to such needs by providing information in the shortest possible time about the most suitable management in order to be able to make the best and most efficient use of it.

Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment., (Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Information regarding the epidemiology of spasticity in patients with multiple sclerosis (MS) in Spain is limited. This cross-sectional survey-based study was undertaken to evaluate the symptoms, severity and consequences of MS-related spasticity (MSS) and to estimate the prevalence of MSS overall and according to the degree of severity (mild/moderate/severe). Adult MS patients (n = 8463) from the two main Spanish MS patients' associations were asked to complete a web-based questionnaire. Two thousand six hundred twenty seven responses were received, of which 2029 were valid for analysis. Two thirds were for women. The mean age of respondents was 40.2 years and the mean MS duration was 8.7 years. MSS was reported by 65.7% of respondents with 40% of these rating it as moderate/severe. MS patients with spasticity experienced more symptoms (including greater difficulty walking), consumed more healthcare resources (including care and rehabilitation sessions), and had a higher degree of disability than patients without spasticity. There was a significant correlation between increasing severity of spasticity and worsening of symptoms. Only 42.4% of patients with moderate spasticity and 52.6% of patients with severe spasticity were currently receiving antispasticity medication compared with 69% and 79%, respectively, reported in a similar survey-based study from the United States; this is likely to reflect regional variations in practice. Early and effective treatment of MSS is important to minimise the consequences of spasticity-related symptoms on patients' quality of life and the economic burden on healthcare systems. In appropriate patients, antispastic treatment, including pharmacotherapy and physiotherapy/rehabilitation, may provide such benefits.

A total of 1,220 subjects from Equatorial Guinea living in Spain (median age = 41 years; 453 male and 767 female) was examined for antibodies to human immunodeficiency virus (HIV) and Hepatitis B (HBV), C (HCV), and D (HDV) viruses. Extracted RNA and DNA from the positive samples were used to quantify viral load. The prevalence of HIV antibodies, HCV RNA, and HBV surface antigen (HBsAg) was 10.8% (N = 132), 11.6% (N = 141), and 7.9% (N = 96), respectively. The most prevalent HIV variant was CRF02&#95;AG (38.5%; N = 40). HCV genotype 4 (60%; N = 36) and HBV genotype A3 (32%; N = 8) were the hepatitis variants most frequently found. Superinfection with HDV was seen in 20.9% (N = 24) of HBsAg carriers. A control group of 276 immigrants from other sub-Saharan countries showed similar rates of HIV and HBsAg, although no HCV cases were found. Immigrants constitute a major source of HIV and hepatitis viruses in Spain; therefore, it is important that control measures are intensified.

Introduction: Natalizumab is very effective at reducing relapses and delaying disease progression in patients with relapsing-remitting multiple sclerosis (RRMS). However, treatment has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The aim of this article is to provide a consensus view on the assessment and stratification of these risks, and to improve the management of natalizumab-treated patients., Development: At an initial meeting of experts on multiple sclerosis (the authors of this consensus), the relevant topics of the consensus were determined and assigned for further elaboration. Topics included how to establish benefit and risk in general, stratification for risk of PML, informing patients of benefits/risks, and how to monitor patients during treatment and after discontinuing treatment. During the drafting phase, all available information published or presented at international meetings was reviewed. After a series of review sessions and meetings, the final draft was produced., Conclusions: Although natalizumab is a very effective drug, its use needs to be considered carefully in view of possible adverse effects and the risk of PML in particular. The neurologist should carefully explain the risks and benefits of treatment in terms the patient can best understand. Before starting treatment, baseline laboratory tests and magnetic resonance imaging (MRI) should be available for future comparisons in the event of suspected PML. The risk of PML should be stratified into high, medium and low risk groups according to presence or absence of anti-JC virus antibodies, prior immunosuppressive therapy, and treatment duration. The follow-up, and frequency of MRI scans in particular, should depend on the risk group to which patient belongs. As our understanding of the risk factors for PML develops, it should be possible to offer patients increasingly individualised therapy. This is a consensus that establishes general recommendations, but neurologists must use their clinical expertise to monitor patients individually., (Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier España. All rights reserved.)

Introduction: Amyotrophic lateral sclerosis (ALS) is a disease with very poor prognosis, and a mortality of 50% at 18 months after diagnosis. Multidisciplinary units attempt to improve the quality of life and survival of patients with ALS. The aim of this study is to evaluate every 3 months, over a 24-month period, the outcome of patients treated at the ALS unit since the time of diagnosis., Material and Methods: We performed a prospective observational study of patients treated in the ALS unit following a clinical pathway since the time of diagnosis with quarterly reviews from 2006 to 2010. The age of onset, functional impairment (ALSFRS-r), impairment of respiratory function, dysphagia and signs of depression and/or cognitive impairment were evaluated in relation to the initial location symptoms (bulbar [B], upper limbs [UL], lower limbs [LL])., Results: A total of 42 patients (30 males and 12 females) were evaluated (mean age at onset of 57.97 years old, SD 14.56). There was an even distribution by location of onset of symptoms (B 14 patients, UL 14, LL 14.) Functional impairment (B -26,89 points, UL -22,48 points, LL -22,66 points), the need for use of BIPAP (B 64.28%; UL 35.71%; LL 50%), the presence of dysphagia (B 85.71; UL 42.85; LL 71.42%), signs of depression (B 78.57%; UL 35.71%; LL 64.28%) and cognitive impairment (B 42.85%; UL 21.42; LL 35.71%) was higher at 24 months of progression in patients with bulbar onset. There was no difference in mortality data (23.80% overall)., Conclusions: The treatment in multidisciplinary units does not change the neurological progression of the disease, but increases the survival of ALS patients regardless of their initial onset, emphasising the use of multidisciplinary care., (Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Little information exists about caregivers of persons with multiple sclerosis (MS). Our aims were to describe the characteristics of a sample of caregivers of persons with MS, assess their perceived burden, health-related quality of life, and investigate factors influencing this burden. We studied 278 caregivers of persons with MS, recruited from a Spanish cross-sectional survey, measuring health-related quality of life by the 36-Item Short-Form Health Survey (SF-36) and burden by the Zarit Caregiver Burden Interview. Of the caregivers, 56.8% were female and their mean age was 50.1 +/- 12.6 years. Their main relationship with the person with MS was spouse/partner (52.9%) and son or daughter (25.9%). Caregiver General Health, Mental Health, Bodily Pain, and Role-emotional Functioning were the most affected dimensions on the SF-36. Multiple regression analysis showed that independent and significant predictors of burden were Role-emotional Functioning and Vitality dimensions SF-36 scores of caregivers, and the Expanded Disability Status Scale scores. The total adjusted variance explained by these variables (adjusted R(2)) was 0.512. Emotional factors and the disability of the person with MS were major predictors of burden. Psychological and social support should be considered to reduce caregiver burden.

From January to December 1997, stools submitted for routine culture were also screened for E. coli O157:H7 to investigate its incidence in our area. Bloody and non-bloody stools were studied. E. coli O157:H7 was not recovered from any of the samples tested. We believe, therefore, that we are in a low rate of infection area, and accordingly do not recommend routine screening of this pathogen.

We report the evolution of the antimicrobial resistance of non-typhi Salmonella (1992-1994) in a Spanish hospital in relation with a case of infection due to a fluoroquinolone-resistant strain of Salmonella ser. Typhimurium. None of the isolates were resistant to ciprofloxacin. The resistance to ampicillin has increased from 20.6% (1992) to 29.5% (1994) whereas no significative differences in chloramphenicol and cotrimoxazole susceptibility were noted.

Background: A prospective study was performed during three years with 76 children hospitalized with the diagnose of rotaviral gastroenteritis. The aim of our study were to evaluate the clinical features of the rotaviral gastroenteritis, the excretion time of rotavirus in stools and the nosocomial rotavirus infection., Methods: The detection of the rotaviral antigen in stool was performed using a rapid test based on latex aglutination (Rotalex). For the determination of the excretion time of rotavirus in stools the test was performed daily in 69 children until the results was negative. Furthermore, a clinical study of the patients was carried out., Results: In 39 cases (51.3%) the gastroenteritis was acquired in the community and 37 cases (48.7%) were nosocomially acquired. The most frequent clinical presentation was an acute diarrhea (96%) with vomiting (63.2%) and fever (63.2%). Only three patients did not have diarrhea. The mean duration of diarrhea was between 3-4 days with a highest duration of 10 days. Most of the patients (58%) had an excretion time of rotaviral antigen lower or equal than 3 days, with an extreme value of 14 days., Conclusions: In our study rotaviral infection occurred mainly in the cooler winter months and in children younger than 6 months of age. A high nosocomial infection level (48.7%) was detected. Vomiting often preceded the onset of diarrhea and fever. The excretion time of rotaviral antigen was independent of the clinical course.

An epidemiological study on toxocariasis in children was carried out at our hospital (Madrid, Spain) in relation with a case of toxocariasis in a child with chronic hypereosinophilia. The study was based on a positive result of the ELISA test, using excretory-secretory antigen from Toxocara canis. The seroprevalence in children was 1%.