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Esclerosis múltiple; Reacciones adversas; Infecciones respiratorias Esclerosi múltiple; Reaccions adverses; Infeccions respiratòries Multiple sclerosis; Adverse reactions; Respiratory infections 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

IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS. RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P

Introduction: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. Development: PR-fampridine dosed at 10 mg every 12 hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. Conclusions: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS. (C) 2015 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license.

Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. Development: PR-fampridine dosed at 10 mg every 12 hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. Conclusions: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS

The effectiveness of disease-modifying drugs in the treatment of multiple sclerosis is associated with adherence. RebiSmart® electronic device provides useful information about adherence to the treatment with subcutaneous (sc) interferon (IFN) ß-1a (Rebif®). The aim of the study was to determine long-term adherence to this treatment in patients with relapsing- remitting multiple sclerosis (RRMS). This retrospective multicentre observational study analysed 258 patients with RRMS who were receiving sc IFN ß-1a (Rebif®) treatment by using RebiSmart® until replacement (36 months maximum lifetime) or treatment discontinuation. Adherence was calculated with data (injection dosage, time, and date) automatically recorded by RebiSmart®. Patients in the study had a mean age of 41 years with a female proportion of 68%. Mean EDSS score at start of treatment was 1.8 (95% CI, 1.6-1.9). Overall adherence was 92.6%(95% CI, 90.6-94.5%). A total of 30.2% of patients achieved an adherence rate of 100%, 80.6% at least 90%, and only 13.2% of patients showed a suboptimal adherence (

For the seventh year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain). Renowned specialists in multiple sclerosis and national leaders in this area have gathered once again to discuss the novelties presented at the 2014 ECTRIM-ACTRIMS World Congress. That meeting gave rise to this review, which will be published in two parts. One of the main conclusions in this first part is the deeper understanding of the genetic component of multiple sclerosis that we are acquiring, although it is still insufficient unless we bear in mind its interaction with the environmental risk factors of the disease or the impact of comorbidity and healthy habits on the patients' susceptibility and prognosis. In this respect, the authors insist on the fact that, in clinical practice, the cognitive and psychiatric disorders remain under-diagnosed and are rarely taken into account in clinical research. Yet, although scarce, the evidence we have points to the possible benefits of disease-modifying drugs and alternatives to treatment with selective serotonin reuptake inhibitors. Addressing the sub-populations in multiple sclerosis and variants of the disease enhances the importance of an early accurate diagnosis in order to offer patients a safer and more personalised prognosis and treatment. Paediatric multiple sclerosis is ideal for studying the risk factors of the disease but, given its low prevalence, the use of prospective studies raises a number of doubts and there is a preference for conducting collaborative studies.Revision de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunion Post-ECTRIMS (I).Por septimo año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS. Reconocidos especialistas en esclerosis multiple y lideres de opinion nacionales se han reunido un año mas para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunion se genera esta revision que sale publicada en dos partes. Como principales conclusiones de esta primera parte se destaca el mayor entendimiento del componente genetico de la esclerosis multiple al que estamos asistiendo, el cual no resulta suficiente si no se considera su interaccion con los factores ambientales de riesgo de la enfermedad, ni el impacto de la comorbilidad y de las conductas saludables en la susceptibilidad y pronostico de los pacientes. Al respecto, los autores insisten en que, en la practica clinica, las alteraciones cognitivas y psiquiatricas estan infradiagnosticadas y son poco consideradas en la investigacion clinica; no obstante, la evidencia, aunque escasa, apunta hacia posibles beneficios de los farmacos modificadores de la enfermedad y alternativas al tratamiento inhibidor selectivo de la recaptacion de serotonina. El abordaje de las subpoblaciones en esclerosis multiple y variantes de la enfermedad refuerza la importancia del diagnostico precoz y preciso para ofrecer a los pacientes un pronostico y un tratamiento mas seguros y personalizados. La esclerosis multiple pediatrica es idonea para estudiar factores de riesgo de la enfermedad, pero dada su baja prevalencia, se cuestionan los estudios prospectivos y se aboga por los estudios colaborativos.

[Objective]: Progressive multifocal leukoencephalopathy (PML) is a serious side effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk increases in individuals seropositive for anti–John Cunningham virus (JC) antibodies, with prolonged duration of natalizumab treatment, and with prior exposure to immunosuppressants. We explored whether the presence of lipid‐specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM bands), a recognized marker of highly inflammatory MS, may identify individuals better able to counteract the potential immunosuppressive effect of natalizumab and hence be associated with a reduced risk of developing PML. [Methods]: We studied 24 MS patients who developed PML and another 343 who did not suffer this opportunistic infection during natalizumab treatment. Patients were recruited at 25 university hospitals. IgM bands were studied by isoelectric focusing and immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited at Ramon y Cajal Hospital in Madrid, Spain. [Results]: IgM bands were independently associated with decreased PML risk (odds ratio [OR] = 45.9, 95% confidence interval [CI] = 5.9–339.3, p, This work was supported by grants; PI12–00239 from FIS; Instituto de Salud Carlos III; SAF 2012‐34670, and RD12/0032/0005 from the Spanish Ministry of Economy and Competitiveness; and BMBF grant KKNMS (Competence Net Multiple Sclerosis; H.T.).

Objective: We aimed to report the frequency and implications of antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) in adults with demyelinating syndromes suspicious for neuromyelitis optica (NMO). Methods: Samples from 174 patients (48 NMO, 84 longitudinally extensive myelitis (LETM), 39 optic neuritis (ON), and three acute disseminated encephalomyelitis (ADEM) who presented initially with isolated LETM) were retrospectively examined for AQP4-ab and MOG-ab using cell-based assays. Results: MOG-ab were found in 17 (9.8%) patients, AQP4-ab in 59 (34%), and both antibodies in two (1.1%). Among the 17 patients with MOG-ab alone, seven (41%) had ON, five (29%) LETM, four (24%) NMO, and one (6%) ADEM. Compared with patients with AQP4-ab, those with MOG-ab were significantly younger (median: 27 vs. 40.5 years), without female predominance (53% vs. 90%), and the clinical course was more frequently monophasic (41% vs. 7%) with a benign outcome (median Expanded Disability Status Scale: 1.5 vs. 4.0). In eight patients with paired serum-cerebrospinal fluid (CSF) samples, five had MOG-ab in both samples and three only in serum. Antibody titres did not differ among clinical phenotypes or disease course. MOG-ab remained detectable in 12/14 patients (median follow-up: 23 months) without correlation between titres' evolution and outcome. Conclusion: MOG-ab identify a subgroup of adult patients with NMO, LETM and ON that have better outcome than those associated with AQP4-ab. MOG-ab are more frequently detected in serum than CSF and the follow-up of titres does not correlate with outcome.

In 2013, a larval survey was conducted north and east of the Bahamas aboard the NOAA Ship NANCY FOSTER. Sampling areas were selected based on larval habitat model predictions, and daily satellite analysis of surface temperature and ocean color. Samples were collected at 97 stations, and 18 larval BFT (Thunnus thynnus) were found at 9 stations. Six of these stations came from oceanographically complex regions characterized by cyclonic and anticyclonic gyres. Larvae ranged in size from 3.22mm to 7.58 mm, corresponding to approximately 5-12 days in age. Analysis of satellite derived surface currents and CTD data suggest that these larvae were spawned and retained in this area. Larval habitat models show areas of high predicted abundance extending east to 650 W, but the actual extent of spawning in this area remains unknown., SI

The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting, held in Madrid in October 2013, resulting in this review, to be published in three parts. This first part of the Post-ECTRIMS review presents an update on gender differences in multiple sclerosis (MS) as well as new evidence on the impact of sex hormones on the disease. We should consider that there is still much to discover with regard to the genetic components of the disease. Similarly, possible infections and lifestyle habits are added as triggers of the known environmental risk factors for MS. The interaction between genetics and the environment has been increasingly implicated as a cause of susceptibility to MS. With regard to the mechanisms of inflammation, axo-glial proteins, instead of myelin proteins, may be the early antigenic targets, and B cells have been implicated in the production of cytokines toxic to oligodendrocytes. Chitinase 3-like 1 (CHI3L1) is validated as a prognostic marker of conversion to MS, and immunoglobulin M oligoclonal bands and L-selectin could be incorporated as possible measures of the risk stratification strategy in patients treated with natalizumab.Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).Los datos mas relevantes presentados en la XXIX edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revision, que se publica en tres partes. Esta primera parte de la revision Post-ECTRIMS presenta una vision actualizada de las diferencias de genero en la esclerosis multiple (EM), asi como las nuevas evidencias sobre el impacto de las hormonas sexuales en la enfermedad. Podemos asumir que aun queda mucho por descubrir con relacion al componente genetico de la enfermedad. De la misma manera, a los ya conocidos factores ambientales de riesgo para la EM se unen posibles infecciones y habitos de vida como desencadenantes. La interaccion entre la genetica y el ambiente cada vez cobra mas fuerza como causa de susceptibilidad a la EM. En cuanto a los mecanismos de inflamacion, las proteinas del complejo axoglial pueden ser las dianas antigenicas iniciales en lugar de las proteinas de mielina, y las celulas B se han visto implicadas en la produccion de citocinas toxicas para los oligodendrocitos. La quitinasa 3-like 1 se valida como marcador pronostico de conversion a EM, y las bandas oligoclonales de inmunoglobulina M y la L-selectina podrian incorporarse como posibles medidas dentro de la estrategia de estratificacion del riesgo en pacientes tratados con natalizumab.

Several controlled clinical trials have demonstrated safety, tolerability, and efficacy of galantamine in patients with Alzheimer's disease (AD). We present an observational and multicenter study carried out in Spain. Its main objective was the assessment of the safety and tolerability of galantamine in the treatment of mild to moderately severe dementia of the Alzheimer type under real clinical conditions.The study had five visits over a 6-month period. Titration of galantamine was performed on a standard basis. All the adverse events (AE) reported were recorded. Serious AE were particularly considered. Effectiveness was also assessed covering cognitive, functional, behavioral and sleep domains.723 patients were enrolled but 74 were excluded, a sample of 649 (71% women and 29% men) remaining. A total of 56.3% patients completed all visits. Baseline Mini-Mental mean score was 19,4 (SD: 4,7). Up to 400 AEs were collected from 29.3% of the patients. The commonest AEs were: nausea (9.7%), vomiting (7.1%), dizziness (4.6%), and diarrhea (4.5%). Mini-Mental scores were stable over time and favorable and significant differences in behavioral and sleep evaluations were observed.Galantamine is a safe and well-tolerated treatment, and provides cognitive, functional, and behavioral benefits in patients with mild to moderately severe AD.