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BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease that in many cases produces disability, having a high impact in patients' lives, reducing significantly their quality of life. The aim of this study was to agree on a set of proposals to improve the current management of MS within the Spanish National Health System (SNHS) and apply the Social Return on Investment (SROI) method to measure the potential social impact these proposals would create. METHODS: A Multidisciplinary Working Team of nine experts, with representation from the main stakeholders regarding MS, was set up to agree on a set of proposals to improve the management of MS. A forecast SROI analysis was carried out, with a one-year timeframe. Data sources included an expert consultation, a narrative literature review and a survey to 532 MS patients. We estimated the required investment of a hypothetical implementation, as well as the potential social value that it could create. We calculated outcomes in monetary units and we measured intangible outcomes through financial proxies. RESULTS: The proposed ideal approach revealed that there are still unmet needs related to MS that can be addressed within the SNHS. Investment would amount to 148 million and social return to 272 million , so each euro invested could yield almost 2 of social return. CONCLUSIONS: This study could guide health interventions, resulting in money savings for the SNHS and increases in patients' quality of life.
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Esclerosis Múltiple/terapia , Programas Nacionales de Salud/economía , Valores Sociales , Análisis Costo-Beneficio , Humanos , Inversiones en Salud , Esclerosis Múltiple/economía , EspañaRESUMEN
Introduction: The Spasticity-Plus Syndrome (SPS) in multiple sclerosis (MS) refers to a combination of spasticity and other signs/symptoms such as spasms, cramps, bladder dysfunction, tremor, sleep disorder, pain, and fatigue. The main purpose is to develop a user-friendly tool that could help neurologists to detect SPS in MS patients as soon as possible. Methods: A survey research based on a conjoint analysis approach was used. An orthogonal factorial design was employed to form 12 patient profiles combining, at random, the eight principal SPS signs/symptoms. Expert neurologists evaluated in a survey and a logistic regression model determined the weight of each SPS sign/symptom, classifying profiles as SPS or not. Results: 72 neurologists participated in the survey answering the conjoint exercise. Logistic regression results of the survey showed the relative contribution of each sign/symptom to the classification as SPS. Spasticity was the most influential sign, followed by spasms, tremor, cramps, and bladder dysfunction. The goodness of fit of the model was appropriate (AUC = 0.816). Concordance between the experts' evaluation vs. model estimation showed strong Pearson's (r = 0.936) and Spearman's (r = 0.893) correlation coefficients. The application of the algorithm provides with a probability of showing SPS and the following ranges are proposed to interpret the results: high (> 60%), moderate (30-60%), or low (< 30%) probability of SPS. Discussion: This study offers an algorithmic tool to help healthcare professionals to identify SPS in MS patients. The use of this tool could simplify the management of SPS, reducing side effects related with polypharmacotherapy.
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BACKGROUND: Updated information about self-reported experience and satisfaction with care of MS patients (PwMS) in Spain is scarce. We aim to describe, from PwMS' perspective, the disease impact, the quality of life and the satisfaction level with the social and healthcare support in Spain, and its evolution over the last decade. METHODS: Multicentre observational study, based on a cross-sectional nationwide survey, completed by 432 PwMS in Spain throughout 2018. The results were compared with those of a similar study carried out in 2007 (370 patients), whose database was retrieved as baseline information. RESULTS: 432 patients recruited from 61 neurology units fully completed the study e-survey (mean age: 43.7 years; 71.4% women). The personal profile of patients was largely similar between the 2007 and 2018 samples. The proportion of patients who identified themselves as having relapsing-remitting MS was higher in 2018 (77.1% vs. 56.7 in 2007; p = 0.0001). Overall, 2018 patients considered themselves more labour-active, less disabled, more independent in movement, and as higher family income earners. The proportion of patients satisfied or very satisfied with healthcare services accessibility increased over time (54.9% in 2007 vs. 66.2 in 2018; p = 0.0009). Similarly, more patients considered their health condition to be good or very good in 2018 (55.8% vs. 33.7% in 2007; p = 0.0001). In contrast, there seems to be little progress in social support terms and opportunities equality. CONCLUSIONS: Health condition of PwMS seems to have improved over the last decade, which could be the result of an increasingly effective health care. However, more social protection measures are needed.
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Esclerosis Múltiple , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/terapia , Calidad de Vida , España/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Updated information on the self-perceived biopsychosocial burden and the healthcare experience among people living with multiple sclerosis in Spain is scarce.We aim to describe the self-reported disease experience of patients diagnosed with MS in Spain and to estimate their biopsychosocial burden. METHODS: Multicentre epidemiological study based on a cross-sectional nationwide survey completed by a geographically stratified sample of MS patients in Spain. RESULTS: A total of 490 surveys completed at 61 neurology units across Spain were analysed. Mean age was 43.7 ± 10.0 years (range:21-72), 71.4% were women. Most patients identified themselves as having relapsing-remitting MS (77.1%), 81.9% retained independent mobility. Most patients considered their health condition to be good (39.4%) or very good (13.1%). Mean EuroQoL questionnaire score was 69.2 ± 21.5. Most patients expressed high level of satisfaction with access to and quality of health care. However, 53.7% considered that sadness or depression interfered with their daily life. Concerns about social support were also mentioned. CONCLUSION: Most people living with MS in Spain consider that their health condition is at least good but more psychological support and social protection measures are needed. Insights obtained from this study may help to better manage the condition in the future.
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Esclerosis Múltiple , Adulto , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Músculos , Evaluación del Resultado de la Atención al Paciente , Calidad de Vida , España/epidemiología , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To analyze the variables associated with better functional outcome 3 months after ischemic stroke treated with fibrinolytic agents. MATERIAL AND METHODS: The cases of 63 patients with characteristics leading to activation of a stroke code were analyzed retrospectively. The patients received fibrinolytic therapy in a referral hospital for the western district of Malaga, Spain. We recorded the time until start of fibrinolytic therapy, severity according to the National Institute of Health Stroke Scale (NIHSS) at baseline and at 24 hours, and functional outcome at 3 months according to the modified Rankin Scale. RESULTS: Data for 63 patients with a mean (SD) age of 65 (11) years were included. The mean time until start of fibrinolytic therapy was 151 (42) minutes. The mean NIHSS scores were 15.5 (4.8) points at baseline and 9.1 (7.13) at 24 hours. The mean change in score at 24 hours was 6.3 (5.8) points. The findings of correlation analysis between scores on the modified Rankin scale and other variables were as follows: NIHSS score at 24 hours, ρ = 0.73; P < .01; NIHSS at baseline, ρ = 0.34; P = .01); age, ρ = 0.41; P = .001); time until start of fibrinolysis, ρ = 0.21; P = .09); change in NIHSS score at 24 hours, ρ = -0.61; P = .001). CONCLUSION: The prognosis for the functional recovery of patients given intravenous fibrinolytic therapy after stroke depends on such factors as age, time treatment is started, severity, and the patient's status at 24 hours. The last factor is the one that is most strongly related to prognosis.
OBJETIVO: Analizar las variables que influyen en un mejor pronóstico funcional a los tres meses en un grupo de pacientes con ictus isquémico agudo fibrinolisado. METODO: Se analizaron retrospectivamente 63 pacientes con características de código ictus y que recibieron fibrinolisis en un hospital de referencia de Málaga Oeste. Se determinó el tiempo de inicio de fibrinolisis (TIF), la gravedad del infarto mediante la puntuación NIHSS basal y a las 24 horas y el pronóstico funcional a los 3 meses mediante la escala Rankin modificada (mRS). RESULTADOS: Se incluyeron 63 pacientes, edad media 65 (DE 11) años. El TIF fue de 151 (DE 42) minutos. Se obtuvo una puntuación media en la escala NIHSS basal de 15,5 (DE 4,8) y a las 24 horas de 9,1 (DE 7,13), y una diferencia media de NIHSS a las 24 horas de 6,3 (DE 5,8). Se realizó análisis de correlación entre mRS y NIHSS a las 24 horas (Rho = 0,73; p < 0,01); NIHSS a la llegada (Rho = 0,34; p = 0,01); edad (Rho = 0,41; p = 0,001); TIF (Rho = 0,21; p = 0,09); y diferencia de NIHSS a las 24 h (Rho = 0,61; p = 0,001). CONCLUSIONES: El pronóstico funcional de los pacientes con ictus agudo que reciben tratamiento fibrinolítico endovenoso depende de factores como la edad, el tiempo desde que se administra el tratamiento, la gravedad inicial del infarto y la situación del paciente a las 24 horas, siendo este último el factor el más relacionado con el pronóstico funcional.
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INTRODUCTION: Mesenchymal stem cells (MSCs) are a multipotent population of adult stem cells, which may represent a promising therapeutic approach for neurological autoimmune diseases such as multiple sclerosis. The mouse is the most used species for obtaining and studying the characteristics of MSC and their potential as autologous transplants in pre-clinical models. However, conflicting data have been published disclosing intraspecies variations. The choice of the mouse strain and the tissue source appear, among others, as important factors in the experimental application of MSCs. METHODS: Adipose tissue-derived MSCs obtained from the SJL/JCrl mouse strain (SJL-AdMSC) have been cultured for a long time (from passage 0 up to 15) under controlled experimental conditions, and their growth rate, morphology, stromal and haematopoietic marker expression profiles and differentiation capacity towards adipocytes, osteocytes and chondrocytes have been determined. Moreover, their preclinical efficacy has been assessed by autologous transplant in relapsing-remitting experimental autoimmune encephalomielitis (RR-EAE)-induced SJL mice (a well established mice model for the study of RR-multiple sclerosis). RESULTS: We demonstrate that SJL-AdMSCs show the same fibroblastic shape, growth rate, profile of markers expression and multipotency described for MSCs in every passage evaluated (up to passage 15). Additionally, SJL-AdMSCs ameliorate the RR-EAE course, suggesting that they could modulate disease progression. Moreover, their features studied are fully comparable with the standardized Ad-MSCs obtained from the C57BL/6 mouse strain, which strengthens their use in cell therapy. CONCLUSION: SJL-AdMSCs might be a suitable source of Ad-MSCs for studies related to the properties of MSCs and their application as promising therapeutic tools in autologous transplants in experimental medicine.
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Diferenciación Celular , Encefalomielitis Autoinmune Experimental/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Tejido Adiposo/citología , Animales , Células Cultivadas , Femenino , Ratones , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: The advance in the achievement of effective therapies for multiple sclerosis (MS), the definition of appropriate therapeutic windows and to establish better diagnostic and prognostic biomarkers have become a challenging task for both researchers and clinicians. Some pitfalls in clinical trials might be related to lack of adequacy of the preclinical studies in MS experimental animal models. AIM: To standardize the methodological protocols of experimental models by developing a set of guidelines for preclinical studies by groups of experts from REEM (Spanish Network for MS). DEVELOPMENT: A guide with recommendations for the application of MS models including a detailed assessment of appropriate experimental models taking into account the objective of the study that has been presented. Standards and quality criteria necessary in a preclinical study have been included. CONCLUSIONS: Standardized animal models of MS are essential to increase the success of the preclinical findings in order to transfer them to the clinical practice.
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Encefalomielitis Autoinmune Experimental/terapia , Modelos Animales , Esclerosis Múltiple/terapia , Proyectos de Investigación , Investigación/normas , Animales , Ensayos Clínicos como Asunto , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/fisiopatología , Humanos , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatologíaRESUMEN
AIM: To evaluate the clinical effectiveness and safety of glatiramer acetate for use in routine clinical practice. PATIENTS AND METHODS: A retrospective, observational study was conducted on patients with multiple sclerosis who were treated with glatiramer acetate in clinical practice. The primary outcome was the clinical effectiveness of glatiramer acetate treatment. RESULTS: The study included a total of 104 patients (women, 59.6%; age at onset of glatiramer acetate treatment, 39.9 ± 10.9 years; prior treatment for multiple sclerosis, 30.8%). The patients had received glatiramer acetate treatment for an average of 3.6 ± 1.9 years. During the first year of glatiramer acetate treatment, the relapse rate decreased by 60%. At this time, the number of relapses had decreased for 47 patients (45.1%), 67 patients (68.4%) had not suffered a relapse and 78 patients (75.0%) showed no signs of progression. During the second year of glatiramer acetate treatment, the relapse rate decreased by 70%. At this time, the number of relapses had decreased for 43 patients (41.3%), 63 patients (75.9%) had not suffered a relapse and 59 patients (56.7%) showed no signs of progression. There were no reported relapses or progression in 56 patients (53.8%) and 41 patients (39.4%) during the first and second years of treatment, respectively. Discontinuation of glatiramer acetate was necessary in only three patients. The most common adverse effects included fatigue (28.9%) and spasticity (7.7%). CONCLUSION: This evaluation of glatiramer acetate use in clinical practice supports the effectiveness and the safety profile observed in previously published clinical trial studies.
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Adyuvantes Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Péptidos/uso terapéutico , Adyuvantes Inmunológicos/efectos adversos , Adulto , Anciano de 80 o más Años , Ensayos Clínicos como Asunto , Progresión de la Enfermedad , Femenino , Acetato de Glatiramer , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/prevención & control , Péptidos/efectos adversos , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Multiple sclerosis is the most frequent chronic inflammatory, demyelinating and neurodegenerative disease in young adults, but has no definitive pharmacological treatment. It is a heterogeneous disease from the immunological, neuropathological and clinical point of view, as well as in terms of its response to different therapies. Over the last two decades, pharmacology has focused on developing drugs that are capable of modifying the course of this disease, with the aim of reducing the frequency of the outbreaks and the speed at which the disability produced by the disease progresses. Nevertheless, today, there are no drugs that are capable of offering a curative effect that can fully stabilise the disease, and neuroprotective and neuroreparative strategies are still in their early stages. In this work we carry out a critical review of the different pathogenic paths involved in multiple sclerosis and we discuss the different pharmacological approaches that have been followed, based on the clinical trials that are currently being conducted. In the near future it is to be expected that, first, we will manage to stabilise the disease completely and, later, recover some of the functions altered by this disease. Research is being conducted at such a rate that we have to be optimistic and think that soon we will be able to improve the situation of those who suffer from the disease.
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Esclerosis Múltiple/tratamiento farmacológico , Adenosina Desaminasa/metabolismo , Células Presentadoras de Antígenos/metabolismo , Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Dihidroorotato Deshidrogenasa , Humanos , Lisofosfolípidos/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Proteína Básica de Mielina/metabolismo , FN-kappa B/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Killer cell immunoglobulin-like receptors (KIRs) are regulators of cytolytic activity of natural killer and certain T cells through interactions with human leukocyte antigen (HLA) class I ligands. KIRs have been shown to contribute to the pathogenesis of several autoimmune diseases, but their role in multiple sclerosis (MS) is still unclear. Here we determined the influence of KIR genes and their HLA class I ligands on susceptibility to MS and on the response to interferon-beta treatment in a Spanish population. KIR and HLA genotyping were performed in 200 MS patients and 200 controls. Significantly higher frequencies were found for KIR2DL5 and KIR3DS1 genes in MS patients and the carriage of the KIR2DL1 gene was associated with a higher progression index. Moreover, the frequency of the HLA-Bw4 motif was significantly reduced in MS patients. The KIR2DL1 and HLA-C2 matches were more frequent in MS patients, whereas the KIR3DL1 and HLA-Bw4 matches were more frequent in healthy controls. Nevertheless, non significant associations were found between all the KIR genes and therapeutic response to interferon-beta. Our results confirm that the carriage of HLA-Bw4 is a protective factor in MS and suggest that KIR2DL5 and KIR3DS1 may have a predisposing role in the disease.
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Predisposición Genética a la Enfermedad , Antígenos HLA-B/genética , Esclerosis Múltiple/genética , Receptores KIR/genética , Adolescente , Adulto , Anciano , Femenino , Genotipo , Antígenos HLA-B/inmunología , Humanos , Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Reacción en Cadena de la Polimerasa , Receptores KIR/inmunología , España , Adulto JovenRESUMEN
The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. The age is an important factor related to the course and prognosis of multiple sclerosis (MS). The evolution to progressive disease persists more than 50 years after diagnosis of MS and a reduction in the delay of diagnosis has been detected. Several strategies have been proposed in order to improve the efficacy of magnetic resonance regarding prognosis and course of disease. The studies presented at the Congress reflect the influence of gender on course and severity of disease symptoms, showing an increase of worldwide prevalence of MS in women. Neuroprotective action of estrogen receptor beta has been reported. The genome wide association studies have allowed investigators to identify numerous susceptible alleles. In this regard, HLA class II genes, seems to contribute to genetic risk for developing neutralizing antibodies against beta-interferon. Vitamin D deficiency and Epstein-Barr virus have been highlighted as risk factors for MS in the reported findings. On the subject of the ongoing controversy regarding the role of inflammation and degeneration in MS, several arguments have been found to support the role of CNS autoimmunity to explain the presence of inflammatory phenomenon. The available data hold the potential therapeutic role of mesenchymal cells given the involvement of these stem cells in CNS repair.
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Congresos como Asunto , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Biomarcadores , Diagnóstico Diferencial , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Ambiente , Europa (Continente) , Femenino , Humanos , Estilo de Vida , Masculino , Esclerosis Múltiple/etiología , Esclerosis Múltiple/genética , Regeneración Nerviosa/fisiología , Virosis/complicacionesRESUMEN
Objetivo: Analizar las variables que influyen en un mejor pronóstico funcional a los tres meses en un grupo de pacientes con ictus isquémico agudo fibrinolisado. Material y métodos: Se analizaron retrospectivamente 63 pacientes con características de código ictus y que recibieron fibrinólisis en un hospital de referencia de Málaga Oeste. Se determinó el tiempo de inicio de fibrinolisis (TIF), la gravedad del infarto mediante la puntuación NIHSS basal y a las 24 horas y el pronóstico funcional a los 3 meses mediante la escala Rankin modificada (mRS). Resultados: Se incluyeron 63 pacientes, edad media 65 (DE 11) años. El TIF fue de 151 (DE 42) minutos. Se obtuvo una puntuación media en la escala NIHSS basal de 15,5 (DE 4,8) y a las 24 horas de 9,1 (DE 7,13), y una diferencia media de NIHSS a las 24 horas de 6,3 (DE 5,8). Se realizó análisis de correlación entre mRS y NIHSS a las 24 horas(Rho = 0,73; p < 0,01); NIHSS a la llegada (Rho = 0,34; p = 0,01); edad (Rho = 0,41; p = 0,001); TIF (Rho = 0,21;p = 0,09); y diferencia de NIHSS a las 24 h (Rho = 0,61; p = 0,001). Conclusión: El pronóstico funcional de los pacientes con ictus agudo que reciben tratamiento fibrinolítico endovenoso depende de factores como la edad, el tiempo desde que se administra el tratamiento, la gravedad inicial del infarto y la situación del paciente a las 24 horas, siendo este último el factor el más relacionado con el pronóstico funcional (AU)
Objective: To analyze the variables associated with better functional outcome 3 months after ischemic stroke treated with fibrinolytic agents. Material and methods: The cases of 63 patients with characteristics leading to activation of a stroke code were analyzed retrospectively. The patients received fibrinolytic therapy in a referral hospital for the western district of Malaga, Spain. We recorded the time until start of fibrinolytic therapy, severity according to the National Institute of Health Stroke Scale (NIHSS) at baseline and at 24 hours, and functional outcome at 3 months according to the modified Rankin Scale. Results: Data for 63 patients with a mean (SD) age of 65 (11) years were included. The mean time until start of fibrinolytic therapy was 151 (42) minutes. The mean NIHSS scores were 15.5 (4.8) points at baseline and 9.1 (7.13) at 24hours. The mean change in score at 24 hours was 6.3 (5.8) points. The findings of correlation analysis between scores on the modified Rankin scale and other variables were as follows: NIHSS score at 24 hours, ρ = 0.73; P < .01; NIHSS at baseline, ρ = 0.34; P = .01); age, ρ = 0.41; P = .001); time until start of fibrinolysis, ρ = 0.21; P = .09); change in NIHSS score at 24 hours, ρ = 0.61; P = .001). Conclusions: The prognosis for the functional recovery of patients given intravenous fibrinolytic therapy after stroke depends on such factors as age, time treatment is started, severity, and the patients status at 24 hours. The last factor34-38 im/tab is the one that is most strongly related to prognosis (AU)
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Humanos , Ataque Isquémico Transitorio/epidemiología , Fibrinolíticos/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Tiempo/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de RiesgoRESUMEN
Introducción. Las baterías actuales, como la Brief Repeatable Battery of Neuropsychological Tests (BRB-N) para la evaluación del deterioro cognitivo en pacientes con esclerosis múltiple, son complejas y consumen mucho tiempo. Objetivo. Obtener valores normativos y validar una nueva batería. Sujetos y métodos. Se incluyeron cuatro tests neuropsicológicos (test de memoria episódica, test de símbolos y dígitos, prueba de evocación categorial y adaptación del Paced Auditory Serial Addition Test). Los valores normativos (en general y por grupo de edad) se dedujeron tras administrar la batería de tests a 1.036 sujetos sanos (el percentil 5 se consideró el límite de la normalidad estadística). La validez externa se obtuvo a través de la comparación con la BRB-N. La nueva batería también se administró a una submuestra de controles sanos después de cuatro semanas para evaluar la reproducibilidad. Resultados. Se reclutaron 1.036 sujetos sanos para proporcionar datos normativos. El tiempo promedio para finalizar la batería neuropsicológica breve fue de 18,5 ± 5,2 minutos. Estadísticamente no se encontraron diferencias significativas entre las puntuaciones de los 229 sujetos a los que se les administró la nueva batería y la BRB-N, excepto por el tiempo promedio de finalización (19 ± 4 frente a 25 ± 5 minutos). En el estudio de reproducibilidad no hubo diferencias significativas excepto en los tests de memoria. Conclusión. Los resultados en la nueva batería y en la BRB-N guardaban una elevada correlación, aunque la nueva batería se podría preferir en la práctica clínica por su sencillez, la facilidad con la que se administra y porque lleva menos tiempo completarla (AU)
Introduction. The current batteries such as the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for evaluating cognitive decline in patients with multiple sclerosis are complex and time-consuming. Aim. To obtain normative values and validate a new battery. Subjects and methods. Four neuropsychological tests were finally included (episodic memory, the Symbol-Digit Modalities Test, a category fluency test, and the Paced Auditory Serial Addition Test). Normative values (overall and by age group) were derived by administering the battery to healthy subjects (5th percentile was the limit of normal). External validity was explored by comparison with the BRB-N. The new battery was also administered to a subsample after 4 weeks to assess reproducibility. Results. To provide normative data, 1036 healthy subjects were recruited. The mean completion time was 18.5 ± 5.2 minutes. For the 229 subjects who were administered the new battery and the BRB-N, no statistically significant differences were found except for mean completion time (19 ± 4 vs 25 ± 5 minutes). In the reproducibility study, there were no significant differences except in the memory tests. Conclusion. The scores on the new battery and the BRB-N were strongly correlated although the shorter completion time and ease of administration could make the new battery preferable in clinical practice (AU)
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Humanos , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas/normas , Trastornos del Conocimiento/diagnóstico , Valores de ReferenciaRESUMEN
Resumen. La esclerosis múltiple es la enfermedad inflamatoria, desmielinizante y neurodegenerativa crónica más frecuente en jóvenes adultos, pero carece de un tratamiento farmacológico definitivo. Es una enfermedad heterogénea, desde el punto de vista inmunológico, neuropatológico y clínico, al igual que lo es su respuesta a las distintas terapias. Durante las últimas dos décadas, la farmacología ha centrado sus esfuerzos en el desarrollo de fármacos modificadores del curso de esta enfermedad, con el objetivo de reducir la frecuencia de los brotes y la velocidad de progresión de la discapacidad que produce la enfermedad. Sin embargo, hoy día no disponemos de un fármaco capaz de presentar un efecto curativo que estabilice por completo la enfermedad, y las estrategias neuroprotectoras y neurorreparadoras están en sus inicios. En este trabajo realizamos una revisión crítica de las diferentes vías patogénicas que participan en la esclerosis múltiple y discutimos las diferentes aproximaciones farmacológicas realizadas, basándonos en los ensayos clínicos que están actualmente en desarrollo. Es previsible que en un futuro próximo consigamos, primero, estabilizar por completo la enfermedad y, más adelante, recuperar parte de las funciones alteradas que ocasiona esta enfermedad. La investigación tiene lugar a tal ritmo que sólo se puede ser optimista y pensar que seremos capaces de mejorar pronto la situación de las personas que padecen la enfermedad (AU)
Summary. Multiple sclerosis is the most frequent chronic inflammatory, demyelinating and neurodegenerative disease in young adults, but has no definitive pharmacological treatment. It is a heterogeneous disease from the immunological, neuropathological and clinical point of view, as well as in terms of its response to different therapies. Over the last two decades, pharmacology has focused on developing drugs that are capable of modifying the course of this disease, with the aim of reducing the frequency of the outbreaks and the speed at which the disability produced by the disease progresses. Nevertheless, today, there are no drugs that are capable of offering a curative effect that can fully stabilise the disease, and neuroprotective and neuroreparative strategies are still in their early stages. In this work we carry out a critical review of the different pathogenic paths involved in multiple sclerosis and we discuss the different pharmacologicalapproaches that have been followed, based on the clinical trials that are currently being conducted. In the near future it is to be expected that, first, we will manage to stabilise the disease completely and, later, recover some of the functions altered by this disease. Research is being conducted at such a rate that we have to be optimistic and think that soon we will be able to improve the situation of those who suffer from the disease (AU)
Asunto(s)
Humanos , Esclerosis Múltiple/tratamiento farmacológico , Drogas en Investigación , Fármacos Neuroprotectores/uso terapéutico , Enfermedades Desmielinizantes/fisiopatología , Esclerosis Múltiple/fisiopatologíaRESUMEN
Resumen. Las novedades presentadas en el XXVI Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2010 en la ciudad sueca de Gotemburgo, han sido resumidas durante la tercera edición de la reunión Post-ECTRIMS celebrada en Madrid en noviembre de 2010. La edad es un factor muy importante relacionado con el curso y pronóstico de la esclerosis múltiple (EM). La transición a la etapa progresiva persiste más de 50 años después del diagnóstico de EM, y se ha detectado una disminución de la demora en el diagnóstico. Sehan propuesto varias estrategias para poder mejorar la utilidad de la resonancia magnética respecto al pronóstico y al curso de la enfermedad. Los estudios presentados reflejan la influencia del género sobre el curso y gravedad de los síntomas de la enfermedad, observándose un incremento de la prevalencia mundial de EM en mujeres. Se ha destacado la acción neuroprotectora de los ligandos del receptor estrogénico beta. Los estudios genéticos de asociación han permitido identificar numerosos alelos susceptibles. En este sentido, los genes del complejo mayor de histocompatibilidad de clase II parecen contribuir al riesgo genético de desarrollar anticuerpos neutralizantes contra el interferón beta. Se ha destacado, además, el déficit de la vitamina D y la infección por virus de Epstein-Barr como factores de riesgo para la EM en los estudios realizados. En relación con la controversia generada en torno al papel de la inflamación y la degeneración en la EM, se han expuesto argumentos a favor de la autoinmunidad para explicar la presencia de fenómenos inflamatorios. Los estudios realizados apoyan el potencial efecto terapéutico de las células mesenquimales, dada su implicación en la reparación del sistema nervioso central(AU)
Summary. The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. The age is an important factor related to the course and prognosis of multiple sclerosis (MS). The evolution to progressive disease persists more than 50 years after diagnosis of MS and a reduction in the delay of diagnosis has been detected. Several strategies have been proposed in order to improve the efficacy of magnetic resonance regarding prognosis and course of disease. The studies presented at the Congress reflect the influence of gender on course and severity of disease symptoms, showing an increase of worldwide prevalence of MS in women. Neuroprotective action of estrogen receptor beta has been reported. The genome wide association studies have allowed investigators to identify numerous susceptible alleles. In this regard, HLA class II genes, seems to contribute to genetic risk for developing neutralizing antibodies against beta-interferon. Vitamin D deficiency and Epstein-Barr virus have been highlighted as risk factors for MS in the reported findings. On the subject of the ongoing controversy regarding the role of inflammation and degeneration in MS, several arguments have been found to support the role of CNS autoimmunity to explain the presence of inflammatory phenomenon. The available data hold the potential therapeutic role of mesenchymal cells given the involvement of these stem cells in CNS repair (AU)
Asunto(s)
Humanos , Esclerosis Múltiple , Historia Natural de las Enfermedades , Distribución por Sexo , Predisposición Genética a la Enfermedad , Progresión de la Enfermedad , Regeneración Nerviosa , Biomarcadores , Virosis/complicacionesRESUMEN
Resumen. Las novedades presentadas en el XXVI Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2010 en la ciudad sueca de Gotemburgo, han sido resumidas en la tercera edición de la reunión Post-ECTRIMS celebrada en Madrid en noviembre de 2010. Se han presentado los prometedores resultados de la extensión a cinco años del estudio PreCISe, que confirman la importancia del tratamiento temprano con acetato de glatiramero en pacientes con síndrome clínicamente aislado (SCA) frente a la conversión a esclerosis múltiple (EM) clínicamente definida y la atrofia cerebral, con una seguridad y tolerabilidad adecuadas. Respecto a la decisión de tratamiento con terapia de escalado o inducción, se proponen diferentes estrategias, dependiendo de las características del SCA. Por otro lado, varios estudios han demostrado el papel favorable de la terapia combinada en pacientes con EM remitente-recurrente sobre la tasa de brotes, pero no sobre parámetros de resonancia magnética. Las nuevas terapias, como alemtuzumab, daclizumab ofatumumab u ocrelizumab, han mostrado resultados esperanzadores de eficacia. No obstante, los resultados de seguridad han detectado varios efectos adversos graves, entre los que destacan las infecciones oportunistas, como la leucoencefalopatía multifocal progresiva causada por el virus JC, asociada principalmente al tratamiento con natalizumab. En este sentido, los clínicos deberán valorar el beneficio-riesgo de estas nuevas terapias al decidir el tratamiento adecuado para cada paciente en el ámbito de la práctica clínica. En este contexto, la detección de anticuerpos antivirus JC mediante un nuevo ELISA podría proporcionar a los clínicos una herramienta útil para estratificar el riesgo de desarrollar leucoencefalopatía multifocal progresiva en los pacientes. En relación con las terapias no farmacológicas, la terapia conductual ha resultado eficaz en el tratamiento de la depresión en la EM, demostrando beneficios adicionales sobre la fatiga, la discapacidad y la adhesión a los tratamientos (AU)
Summary. The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. Encouraging findings from the 5-years follow up extension from PreCISe study confirm the benefit of early treatment with glatiramer acetate in patients with clinically isolated syndromes (CIS) against the conversion to clinically definitive multiple sclerosis and cerebral atrophy with an adequate safety and tolerability. Regarding treatment decision with escalation or induction therapy, different strategies have been proposed depending on to the characteristics of the individual patient with CIS. Findings from several of the reported studies have revealed the favorable role of combined therapy on relapse rate but not on magnetic resonance parameters in patients with recurrentremittent multiple sclerosis. Novel therapies such as alemtuzumab, daclizumab ofatutumab or ocrelizumab have shown promising findings regarding efficacy. Nevertheless, safety findings for these emerging therapies have detected some severe adverse events, the main ones being potentially fatal opportunistic infections such as progressive multifocal leukoencephalopathy (PML) caused by JC virus, mainly linked to natalizumab treatment. In this regard, clinicians will face the assessment of he benefit-risk ratio when deciding on the adequate treatment for each patient in the clinical setting. In this regard, determination of antibodies to JC virus by a novel two-step enzyme-linked immunosorbent assay (ELISA) could provide clinicians with a useful tool to stratify PML risk in patients. Regarding non pharmacologic therapies, behavioral intervention has emerged as an effective therapy in the treatment of depression in multiple sclerosis, showing additional benefits on fatigue, disability and adherence to treatment (AU