Prospective memory in patients with relapsing remitting Multiple Sclerosis

Prospective Memory (PM) is a set of cognitive abilities that allow us to remember to perform planned actions or delayed intentions. It requires the recall of the content of the planned task in the form of an intention to be able to execute it at the 4 appropriate moment. Previous studies have yielded conflicting results as some show that MS patients have difficulty in remembering the content of intentions and others in the process of self-initiation of delayed intentions. Moreover, the relationship between PM and clinical variables also remains unclear. The aim of this study is to investigate PM in Relapsing-Remitting Multiple Sclerosis (RRMS) with two experimental tests that evaluate different aspects of the MP. Another aim of the current study was to analyse the relationship between PM and demographic variables and clinical variables. Methods: 36 outpatients with a diagnosis of RRMS attending to two centers specialized in multiple sclerosis clinics, were recruited. Thirty five healthy volunteers formed the contrast group (CG), matched for age, gender and education with the MS patients. A neuropsychological test battery that included two techniques for measuring PM was administered. The Cóndor test consists of reading a text whilst simultaneously executing many actions. In the Multitask Prospective Memory (MTPM), the participant must remember to initiate a complex intention, which was previously planned. The test yields formation scores of the intention, initiation, plan retention capacity and finally two execution scores. A depression scale (Beck Depression Inventory, BDI-II) was administered and physical disability was revealed using the Expanded Disability Status Scale. Results: In the RRMS group, the majority of patients (80.6%) had none or minimal signs of depression according to BDI-II classification criteria. Seventy five % of patients were in full- or half-time employment, 13.9% were unemployed or in occasional employment and 11.1% were house wives or retired on grounds of age. With respect to cognitive performance 47.2% of MS patients presented cognitive impairment. RRMS patients and the CG did not differ significantly on age and years of formal education. Groups showed no significant differences in distribution of Gender. Patients scored significantly lower than the CG on the Cóndor?s total score, p = 5 .007, d = 0.7. On the MTPM, the CG obtained significantly more points for intention formation than patients, p = .027, d = 0.5. Sixty-three percent of patients versus 88.5% of the CG self-initiated the intention, p = .014. Patients who obtained a higher score on Formation, self-initiated more often, p = .012. Education, disease progression and depression measure with the Beck Depression Inventory, significantly and mildly correlate with the Cóndor and the MTPM. Physical disability was only associated with the intention planning phase of MTPM. Conclusion: PM appears to be impaired in patients with RRMS. A deficit was found in planning and self-initiation of planned actions. Self-initiation was influenced by planning quality. Education, disease progression and depression were shown to influence recall and execution of future intentions. Physical disability was only associated with the intention planning phase. Some previous studies have not found a significant relationship between physical disability and cognitive measures. This study suggests that PM can be affected in patients with a low level of physical impairment. Results highlight the need for objective assessment of PM in RRMS patients to be able to detect any disorder in the initial stages of the disease and start appropriate rehabilitation. Amongst the limitations of this study, the observational, non-blind design must be acknowledged, as well as the small sample size. Also, the instruments used to assess PM are relatively new and studies of their psychometric properties are lacking. Nevertheless, the use of an instrument like El Cóndor is notable, given that it was developed for local population.Fil: Cores, Evangelina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vanotti, Sandra Ines. Universidad de Buenos Aires. Facultad de Psicología; Argentina. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Orlando, Garcea. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Osorio, Mabel. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Politis, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentin

Impaired performances in a stimulus for relapsing-remitting multiple sclerosis patients versus controls

The objectives of this study were to determine whether patients with Multiple Sclerosis(MS) have difficulties in a stimulus equivalence task, and to assess the potential relationshipbetween their difficulties and cognitive impairment. A total of 12 MS patients and matchedcontrols completed the stimulus equivalence task. Patients with MS also completedmeasures of a neuropsychological evaluation that included the Brief Repeatable Battery inMultiple Sclerosis, Trail Making A and B, the Wechsler Adult Intelligence (Digit Span), theWisconsin Card Sorting Test, the California Verbal Learning Test, the Wechsler MemoryScale (Logic Memory), and the Boston Naming Test. The stimulus equivalence taskshowed that MS patients had poorer performance and slower response times as comparedwith controls in the stimulus equivalence task. There was a significant correlation amongstimulus equivalence task parameters and indexes of executive function and memory fromthe neuropsychological evaluation.Fil: Vanotti, Sandra Inés. Universidad de Buenos Aires; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Tabullo, Angel Javier. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cores, Evangelina Valeria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fiorentini, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires; ArgentinaFil: Garcea, Orlando. Universidad de Buenos Aires; ArgentinaFil: Yorio, Alberto. Universidad de Buenos Aires. Facultad de Psicología; Argentin

Prospective study of memory in patients with brain injury

Introducción: La capacidad de recordar realizar una acción en el futuro o de evocar intenciones demoradas, también llamada Memoria Prospectiva (MP), ha sido objeto de estudio de numerosas investigaciones dentro del marco de la neuropsicología en los últimos años debido a la importancia de la indemnidad de esta habilidad para desarrollar una vida independiente. Estas investigaciones han dado el resultado de un gran avance en el conocimiento del rendimiento de MP de los pacientes con distintas enfermedades neurológicas: traumatismo de cráneo; Enfermedad de Parkinson; Demencia de Tipo Alzheimer; Esclerosis Múltiple; Epilepsia; Síndrome de inmunodeficiencia Adquirida; Síndrome de Korsakoff; Encefalitis Herpética; y Accidente Cerebro Vascular. A su vez estos estudios realizan sus aportes al desarrollo de modelos teóricos de MP. Objetivos: En este artículo se revisan estudios neuropsicológicos en MP de los últimos diez años y su implicancia sobre los modelos teóricos de MP así como la utilidad de los descubrimientos en el desarrollo de estrategias terapéuticas de neurorehabilitación cognitiva. Desarrollo: Se describen las investigaciones dentro de cada patología resaltando el aspecto de la MP analizado, tratando de integrar los distintos desarrollos. Conclusiones: Se realizan conclusiones acerca del estado de avance en este campo, se exponen las limitaciones de un estudio de revisión en esta área y se sugieren direcciones futuras de la investigación.Introduction: The ability to remember to perform an action in the future or delayed intentions, also called prospective memory (PM) has been the object of many researches during the last years in the area of neuropsychology because of the relevance of its indemnity for an independent life. This research had result in a growing amount of knowledge about the performance in PM of patients with several distinct diseases like traumatic brain impairment, Alzheimer’s dementia, Parkinson’s disease, multiple sclerosis, epilepsy, etc. At the same time, those studies had made important contributions to the development of PM theoretical models. Goal: This research intends to review the studies on neuropsychology of PM of the last decade, its importance in PM theory and the applicancy in cognitive neurorehabilitation. Development: Research is described in each pathology highlighting the aspect of PM taken into consideration and trying to integrate them. Conclusions: Conclusions are made about advances in the field, exposing the limits of a review in this area. Future directions are suggested.Fil: Cores, Evangelina Valeria. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vanotti, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Garcea, Orlando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Politis, Daniel Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Paradigmas experimentales de evaluación de la Memoria Prospectiva en el laboratorio

Los estudios de la Memoria Prospectiva (MP) en las áreas de psicología cognitiva, gerontología y neuropsicología utilizan diversos paradigmas de evaluación. De estos paradigmas surgen discrepancias por los diferentes procesos mentales implicados en las tareas de MP . Estas distinciones deben ser consideradas por los científicos en el momento de elegir la tarea experimental en un diseño de investigación. El objetivo de este artículo es describir las variables de agrupación de las tareas experimentales utilizadas en la literatura para medir la MP. Se realiza una reseña de los principales estudios haciendo hincapié en las características de las tareas implementadas actualmente. Se distinguen por lo menos nueve dimensiones: la naturaleza del estímulo que inicia la acción, es decir el pasaje de un periodo de tiempo en el caso de intenciones relacionadas con tiempo y la llegada de una señal del ambiente para aquellas relacionadas con eventos, la complejidad de la tarea concurrente así como de las tareas de MP, la relación entre la tarea concurrente y la de MP diferenciando entre paradigmas de procesamiento focal y no-focal, el efecto de asociación entre la intención y la señal disparadora de la intención, el grado de conciencia de los sujetos acerca de la evaluación de la MP, el uso de acciones vs. respuestas verbales como intenciones, la implementación de tareas ultiintencionales vs. tareas de intención única, la evaluación específica de la planificación de intenciones y por último las modificaciones para mejorar la performance en MP. Se resumen las disquisiciones acerca de los procesos cognitivos implicados.Prospective memory (PM) research in the areas of Cognitive Psychology, Gerontology and Neuropsychology implements different assessment paradigms. Differences between this paradigms results in unlike implicated mental processes. This disctintions should be taken into account when choosing the experimental task of a research design. This study aims to describe the grouping variables of experimental task used in the literature to meassure PM. Studies in PM highlighting the properties of currently used tasks are reviewed. It can be distinguish at least nine dimensions: the nature of the stimuli that triggers the intended action, this means the pasage of time in the case of time-based intentions, and an enviromental sign in the case of event-based intentions, complexity of the ongoing task and the PM task, the relationship between the ongoing task and PM task spliting focal and nonfocal processing, the effect of association between intention and the triggering sign, participants degree of awareness about PM evaluation, use of actions vs. verbal responses as intentions, employment of multitasking vs. a single intention, the specific assessment of intention planning, and finally changes that improve PM performance. Disquisitions about cognitive processes are summarize.Fil: Cores, Evangelina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Vanotti, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Politis, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Garcea, Orlando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentin

Prospective memory and quality of life in relapsing-remitting multiple sclerosis patients

La calidad de vida relacionada con la salud (CVRS) es un constructo complejo concerniente al bienestar percibido por el paciente sobre los dominios de la salud. La CVRS y la memoria prospectiva se encuentran afectados en pacientes con esclerosis múltiple. El objetivo del presente trabajo es estudiar la relación entre la memoria prospectiva y la CVRS. Se evaluaron 51 pacientes con esclerosis múltiple recurrente remitente. Los instrumentos implementados fueron: una prueba multitarea de memoria prospectiva llamado El Cóndor y una escala de CVRS multidominio llamada Multiple Sclerosis International Quality of Life (MusiQoL). Se encontraron correlaciones significativas y positivas aunque de grado débil entre el Cóndor Total de Éxitos y las medidas del MusiQoL, particularmente con las dimensiones Síntomas (r: .34, p = .014), Relaciones de Amistad (r: .31, p = .024) y Rechazo (r: .37, p = .006), así como con el Índice Global (r: .37, p = .007). El presente estudio es el primero en establecer una relación entre la CVRS y el rendimiento en memoria prospectiva de pacientes con esclerosis múltiple.Health related quality of life (HRQL) is a complex construct concerning the patient’s perceived well-being on the domains of health. HRQOL and prospective memory are affected in multiple sclerosis patients. The aim of this study is to determine the relationship between prospective memory and HRQOL. Fifty one patients with relapsing-remitting multiple sclerosis were assessed. Instruments were a multitasking prospective memory test called El Cóndor; and a multidomain HRQOL scale called the Multiple Sclerosis International Quality of Life (MusiQoL). Significant and positive correlations were found, although weak, between the El Cóndor-Total Hits and the MusiQoL measures, particularly with the dimensions Symptoms (r: .34, p = .014), Friendship Relationships (r: .31, p = .024) and Rejection (r: .37, p = .006), as well as with the Global Index (r: .37, p = .007). This study is the first to demonstrate a relationship between HRQOL and the performance of multiple sclerosis patients in prospective memory.Fil: Cores, Evangelina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Vanotti, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos; ArgentinaFil: Osorio, Mabel. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Silva, Berenice Anabel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos; ArgentinaFil: Tabernero, Maria Eugenia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcea, Orlando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos; ArgentinaFil: Politis, Daniel Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

TNFSFR1A R92Q mutation, autoinflammatory symptoms and multiple sclerosis in a cohort from Argentina

Systemic autoinflammatory diseases are genetic disorders characterized by seemingly unprovoked inflammation, without major involvement of the adaptive immune system. Among them it is recognized the TNF receptor associated periodic syndrome (TRAPS) caused by mutations in the TNFRSF1A gene and characterized by symptoms such as recurrent high fevers, rash, abdominal pain, arthralgia and myalgia. Recent studies have recognized the potential role of TNFRSF1A mutations in Multiple Sclerosis (MS). Our aim was to investigate the role of TNFRSF1A R92Q gene mutation in a cohort of 90 Argentinean MS patients, where we determined the frequency of the TNFRSF1A R92Q mutation. We also compared autoinflammatory symptoms, MS clinical characteristics and treatment response and tolerability in R92Q carriers and non-carriers. Also, we used a case-control study design to obtain the genotypes of 78 healthy controls and assess the role of this mutation as a risk factor for MS. We found that five patients (5.5%) carried the R92Q mutation, four reported autoinflammatory symptoms previous to MS onset. We found no differences in MS clinical features, treatment response and tolerability between carriers and non-carriers. R92Q mutation was more frequent in MS patients as compared to controls. This increases the risk to develop MS in about 4.5 times. The TNFRSF1A R92Q mutation is a common finding in Argentinean MS patients. This genetic variant might be a risk factor for MS. © 2011 Springer Science+Business Media B.V.Fil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Sanatorio Franchin; ArgentinaFil: González Morón, Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Garcea, Orlando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Villa, Andrés María. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentin

Influence of working memory in two tests used for episodic memory assessment in multiple sclerosis

La memoria episódica es la capacidad de recordar eventos y experiencias personales, contextualizables en tiempo y espacio. La memoria de trabajo es un sistema activo de almacenamiento temporal y de manipulación de la información. En la evaluación de la memoria episódica verbal en pacientes con Esclerosis Múltiple típicamente se utilizan dos técnicas: el Test Selectivo de Memoria (TSM) y el Test de Aprendizaje Verbal de California (TAVC). Ha sido sugerido que las diferencias entre las técnicas podrían asociarse en distinto grado a las demandas de memoria de trabajo durante el desempeño, el presente estudio intenta probar esta hipótesis. Método: 33 pacientes con Esclerosis Múltiple fueron evaluados con el TSM, el TAVC, Dígitos Inverso y el Paced Auditory Serial Addition Test (PASAT). Resultados: Se halló una correlación significativa y directa entre PASAT y TSM (r = .56, p = .001). En el análisis de regresión logística, sólo el TSM (R2 = .315, F = 13.790, p < .01) resultó ser predictor del PASAT. Discusión: Estos resultados indican que la memoria de trabajo influencia en mayor medida el desempeño en el TSM en comparación con el TAVC. Esta información debe ser tenida en cuenta al analizar los resultados de una evaluación neuropsicológica en pacientes con Esclerosis Múltiple.La mémoire épisodique est la capacité de se rappeler des événements et des expériences, contextualizables dans le temps et l'espace. La mémoire de travail est un système de stockage et de manipulation de l'information temporaire active. Dans l'évaluation de la mémoire épisodique verbale chez les patients atteints de sclérose multiple utilise généralement deux techniques: Test de la mémoire sélective (TSM) et le Verbal Learning Test de Californie (TAVC). Il a été suggéré que les différences entre les techniques peuvent être associées à des degrés divers aux exigences de mémoire de travail au cours de l'exercice, les tentatives actuelles d'étude pour tester cette hypothèse. Trente-trois patients atteints de sclérose multiple ont été évalués avec le TSM, le TAVC, chiffres Inverse et rythmé Auditory Serial Addition Test (PASAT). Nous avons trouvé une corrélation significative et directe entre PASAT et SST (r = .56, p = .001). En analyse de régression logistique, seule la TSM (R2 = .315, F = 13.790, p <.01) était un facteur prédictif de la PASAT. Ces résultats indiquent que la mémoire de travail de plus d'influence sur les performances par rapport TSM et TAVC. Cette information doit être prise en compte lors de l'analyse des résultats d'une évaluation neuropsychologique chez les patients atteints de sclérose multiple. Mot clefs: la sclérose multiple, mémoire à long terme, mémoire de travail, mémoire épisodique, tests neuropsychologiques.A memória episódica é o sistema de memória relacionada à habilidade de recordar eventos e experiências pessoais, contextualizadas no tempo e no espaço. A memória de trabalho é um sistema ativo de armazenamento temporal e de manipulação da informação. Na avaliação da memória episódica verbal em pacientes com esclerose múltipla tipicamente utilizam-se duas técnicas: o Teste Seletivo de Memória (TSM) e o Teste de Aprendizagem Verbal de Califórnia (TAVC). Sugeriu-se que as diferenças entre as técnicas podem ser associadas em graus variados com a demanda da memória de trabalho durante o desempenho. O presente estudo visa a investigar esta hipótese. Trinta e três pacientes com esclerose múltipla foram avaliados com o TSM, o TAVC, dígitos – ordem inversa e o Paced Auditory Serial Addition Test (PASAT). Dentre os principais achados, encontrou-se uma correlação significativa e direta entre os escores de PASAT e TSM (r= 0,56, p= 0,001). A análise de regressão logística mostrou que apenas o escore do TSM (R2= 0,315, F= 13,790, p < 0,01) resultou ser preditor do PASAT. Estes resultados indicam que a memória de trabalho influencia em maior medida o desempenho no TSM em comparação com o TAVC. Esta informação deve ser considerada ao se interpretar os resultados de uma avaliação neuropsicológica em pacientes com esclerose múltipla.Episodic memory is a system of memory related to the ability to recall events and experiences, contextualized in time and in space. Working memory is an active system of temporary storage and manipulation of information. The evaluation of verbal episodic memory in patients with Multiple Sclerosis typically uses two techniques: Selective Reminding Test (SRT) and California Verbal Learning Test (CVLT). It has been suggested that the differences between the techniques could be associated in varying degrees to the demands of working memory during the performance. This study attempts to test this hypothesis. Thirty-three patients with Multiple Sclerosis were evaluated by means of the SRT, the CVLT, Backwards Digits and the Paced Auditory Inverse Serial Addition Test (PASAT). Among the main findings, a significant and direct correlation between PASAT and SRT scores was found (r = .56, p = .001). In logistic regression analysis, only the score of SRT (R2 = 0.315, F = 13,790, p < .01) was found to be a predictor of PASAT. These results indicate that working memory influence the performance in SRT more than CVLT. This information should be taken into account when analyzing the results of a neuropsychological evaluation in patients with Multiple Sclerosis. Key words: multiple sclerosis, long term memory, working memory, episodic memory, neuropsychological tests.Fil: Cores, Evangelina Valeria. Gobierno de la Ciudad de Buenos Aires. Hospital Gral.de Agudos "ramos Mejia"; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Peron"; ArgentinaFil: Vanotti, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital Gral.de Agudos "ramos Mejia"; ArgentinaFil: Fiorentini, Leticia. Gobierno de la Ciudad de Buenos Aires. Hospital Gral.de Agudos "ramos Mejia"; ArgentinaFil: Villa, Andrés. Gobierno de la Ciudad de Buenos Aires. Hospital Gral.de Agudos "ramos Mejia"; ArgentinaFil: Garcea, Orlando. Gobierno de la Ciudad de Buenos Aires. Hospital Gral.de Agudos "ramos Mejia"; Argentin

New genetic factors in multiple sclerosis: R92Q mutation in the gene TNFRSF1A TRAPS and autoinflammatory syndrome

Introducción y objetivos: recientes comunicaciones han mostrado la presencia de sintomatología del síndrome autoinflamatorio periódico asociado al receptor tipo 1 para el factor de necrosis tumoral (TRAPS) en pacientes con esclerosis múltiple (EM) portadores de la mutación R92Q en el gen TNFRSF1A. Nuestro objetivo fue investigar la prevalencia de esta mutación en una población argentina de pacientes con EM, describir las manifestaciones clínicas expresadas en estos sujetos y analizar el rol de la misma como factor de susceptibilidad para EM en un estudio de epidemiología molecular. Pacientes y métodos: se investigó la prevalencia de la mutación R92Q mediante PCR-RFLP en una población de 90 pacientes con EM y 78 controles sanos. Se describieron las características clínicas de ambas patologías (EM y TRAPS) en los portadores de la anomalía genética. Se compararon las frecuencias mutacionales entre casos y controles, y se analizaron variables descriptivas del curso clínico y terapéutico de la EM en el grupo de enfermos estratificado según la presencia de la mutación. Resultados: se identificaron 5 pacientes (5,5%) portadores de la mutación TNFRSF1A R92Q. Presentaron un curso clínico y terapéutico característico de su patología neurológica, habiendo experimentado 4 de ellos sintomatología sugestiva de TRAPS previo al inicio de la EM. La mutación R92Q fue más frecuente en la población de enfermos que en los controles sanos (1,3%), sugiriendo que este hecho podría aumentar el riesgo para padecer EM en 4,5 veces aproximadamente. Conclusiones: identificamos en nuestra población 5 pacientes con EM y TRAPS portadores de la mutación R92Q en TNFRSF1A. Esta mutación podría ser uno de los distintos factores de susceptibilidad genéticos implicados en el desarrollo de la EM.Background and aims: Recent studies have recognized a role for TNFRSF1A mutations in Multiple Sclerosis (MS). A number of patients presenting the coexistence of TRAPS (caused by R92Q mutation) and MS were reported. Gene variants in TNFRSF1A might be a genetic risk factor to develop MS. Our aims were: to assess the frequency of TNFRSF1A R92Q mutation in a cohort of MS Argentinean patients and to investigate the role of this mutation in MS clinical characteristics. Secondarily, to investigate the role of this mutation as a genetic risk factor to develop MS. Patients and methods: We investigated in a cohort of 90 MS patients from Argentina the TNFRSF1A R92Q mutation by means of a PCR-RFLP assay. TRAPS symptoms, MS clinical characteristics and treatment response and tolerability were investigated in carriers and non-carriers. Secondarily, 78 healthy controls were genotyped to assess the role of this mutation as a risk factor following a case-control study design. Results: Five patients (5.5%) carried the R92Q mutation. Four of them reported symptoms suggestive of TRAPS previous to MS onset. No differences in MS clinical features and treatment response and tolerability were found between carriers and non-carriers. R92Q mutation was more frequent in patients than controls increasing the risk to develop MS in about 4.5 times. Conclusions: The TNFRSF1A R92Q mutation is not an infrequent finding in MS Argentinean patients that seem to present the coexistence of TRAPS and the demyelinating disease. This genetic variant might be a risk factor to develop MS.Fil: González Morón, Dolores. Sanatorio V. Franchin; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. J. M. Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kauffman, Marcelo Andres. Sanatorio V. Franchin; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. J. M. Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcea, Orlando. Sanatorio V. Franchin; ArgentinaFil: Villa, Andrés María. Sanatorio V. Franchin; Argentin