Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients.

Global methylation correlates with clinical status in multiple sclerosis patients in the first year of IFNbeta treatment.

The alteration of DNA methylation patterns are a key component of disease onset and/or progression. Our objective was to evaluate the differences in Long Interspersed Nuclear Element-1 (LINE-1) methylation levels, as a surrogate marker of global DNA methylation, between multiple sclerosis (MS) patients and healthy controls. In addition, we assessed the association of LINE-1 methylation with clinical disease activity in patients treated with IFNbeta (IFNß). We found that individuals with high levels of LINE-1 methylation showed 6-fold increased risk of suffering MS. Additionally, treated MS patients who bear high LINE-1 methylation levels had an 11-fold increased risk of clinical activity. Moreover, a negative correlation between treatment duration and percentage of LINE-1 methylation, that was statistically significant exclusively in the group of patients without clinical activity, was observed. Our data suggest that in MS patients, a slight global DNA hypermethylation occurs that may be related to the pathophysiology of the disease. In addition, global DNA methylation levels could play a role as a biomarker for the differential clinical response to IFNß.

Validación transcultural al castellano del Actionable Bladder Symptoms Screening Tool / Transcultural validation in Spanish of the Actionable Bladder Symptoms Screening Tool

Introducción. Los trastornos del tracto urinario inferior son frecuentes en pacientes con esclerosis múltiple a lo largo del transcurso de la enfermedad y alcanzan prevalencias variables cercanas al 75%. Es primordial realizar un diagnóstico precoz en fases tempranas y un abordaje terapéutico óptimo. Burks et al elaboraron el Actionable Bladder Symptoms Screening Tool (ABSST) como herramienta de cribado útil de dichos trastornos. Posteriormente, Bates et al desarrollaron una versión corta del ABSST con el objetivo de minimizar el tiempo de realización y facilitar su manejo. Objetivo. Realizar la validación transcultural al castellano de la versión breve del ABSST. Pacientes y métodos. Se realizó la traducción al castellano del ABSST y una posterior retrotraducción al inglés que confirmaba su equivalencia semántica. Se llevó a cabo una prueba de campo en 40 pacientes con esclerosis múltiple, incluyendo dos preguntas finales para comprobar la comprensión y aceptabilidad de la herramienta y un último ítem que recogía el tiempo empleado para su realización. Resultados: Se seleccionaron 40 pacientes conforme a los criterios de inclusión y exclusión; el 67,5% eran mujeres y la media global de edad era de 46,2 años. La comprensión del test fue del 100%, y la aceptabilidad, del 97,5%. El 57,5% obtuvo puntuaciones >= 3, y se emplearon 5,33 minutos de media. Conclusiones. El ABSST como cuestionario de cribado breve de trastornos urinarios en la esclerosis múltiple es una herramienta útil para su detección temprana y queda validado para su uso en castellano (AU)

Introduction. Disorders of the lower urinary tract are frequent in patients with multiple sclerosis throughout the course of the disease and reach variable prevalences close to 75%. It is essential to obtain an early diagnosis in the initial phases and to implement an optimal therapeutic management. Burks et al developed the Actionable Bladder Symptoms Screening Tool (ABSST) as a useful screening test in such disorders. Later, Bates et al developed a short version of the ABSST with the objective of minimising the time required to complete it and making it easier to use. AIMS. To carry out the transcultural validation into Spanish of the short version of the ABSST. Patients and Methods: The ABSST was translated into Spanish and then back-translated into English, which confirmed the semantic equivalence. A field test was conducted on 40 patients with multiple sclerosis, with two extra questions being included at the end in order to check the comprehension and acceptability of the tool, together with a final item that asked for the time spent on completing it. Results: Forty patients were selected In accordance with the eligibility and exclusion criteria; 67.5% of them were females and the overall mean age was 46.2 years. The rate of comprehension of the test was 100%, and that of acceptability was 97.5%. Results showed that 57.5% obtained scores >= 3, and an average of 5.33 minutes were spent on completing it. Conclusions: As a brief screening questionnaire for urinary disorders in multiple sclerosis, the ABSST is a useful tool for detecting them at an early stage and has now been validated for use in Spanish (AU)