The nature of memory impairment in multiple sclerosis: understanding different patterns over the course of the disease

IntroductionMemory deficit is one of the most common and severe cognitive impairments in patients with multiple sclerosis and can greatly affect their quality of life. However, there is currently no agreement as to the nature of memory deficit in multiple sclerosis.MethodsThis cross-sectional study, carried out at the Dr. Josep Trueta and Santa Caterina hospitals in Girona (Spain), was designed to determine the semiology of verbal memory deficit in the different stages of the disease. To this end, a modification of Rey’s verbal auditory test was created by introducing two recognition trials between the five learning trials, thus monitoring what happens in terms of acquisition versus the retrieval of information during the learning phase. Linear regression models were used to evaluate verbal episodic memory performance between-groups adjusting results by age, sex, educational level, and the presence of anxiety and/or depressive symptoms.Results133 patients with multiple sclerosis, clinically isolated syndrome, and radiologically isolated syndrome and 55 healthy controls aged 18–65 years were assessed. It was observed that the memory processes of multiple sclerosis patients worsen with the progression of the disease. In this respect, patients in pre-diagnostic phases (radiologically isolated syndrome and clinically isolated syndrome) show no differences in verbal episodic memory compared to the healthy controls. Patients in the inflammatory stage (relapsing–remitting multiple sclerosis) show a previously learned information retrieval deficit, while patients in progressive stages (secondary progressive multiple sclerosis and primary progressive multiple sclerosis) do not even correctly acquire information.DiscussionThese results provide significant information to assist in understanding the nature of memory deficits in multiple sclerosis over the course of the disease. These results are discussed in terms of possible cognitive rehabilitation strategies depending on the evolutive stage and are related to neuropathological mechanisms involved in the progression of the disease

Assessing the presence of oligoclonal IgM bands as a prognostic biomarker of cognitive decline in the early stages of multiple sclerosis

Bandes oligoclonals; Esclerosi múltiple; Disfunció cognitivaBandas oligoclonales; Esclerosis múltiple; Disfunción cognitivaOligoclonal bands; Multiple sclerosis; Cognitive dysfunctionBackground: An association has been found between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid and a more severe clinical multiple sclerosis course. Objective: To investigate lipid-specific oligoclonal IgM bands as a prognostic biomarker of cognitive impairment in the early stages of multiple sclerosis. Methods: Forty-four patients underwent neuropsychological assessment at baseline and 4 years. Cognitive performance at follow-up was compared adjusting by age, education, anxiety-depression, and baseline performance. Results: LS-OCMB+ patients only performed worse for Long-Term Storage in the Selective Reminding Test (p = .018). Conclusion: There are no remarkable cognitive differences between LS-OCMB- and LS-OCMB+ patients in the early stages of MS

Identificación de genes de susceptibilidad en esclerosis múltiple. Descripción clínica y análisis genético de una extensa familia de etnia gitana (Estudio EMGypsy)

Multiple sclerosis is a chronic disease of the central nervous system which has an unknown aetiology and an autoimmune mechanism. Two pathogenic processes, inflammation and neurodegeneration, converge causing a progressive disorder with a high degree of both physical and cognitive disability. The disease is the most frequent cause of non-traumatic neurological disability in the young adult population in the Western world. Epidemiological and natural history studies show that there is a genetic susceptibility to the disease upon which a number of environmental factors act, generating an imbalance in the immune system that eventually produces a central nervous system attack with the consequent manifestation of the characteristic signs and symptoms of the disease. However, the inherited aspect of the disease has yet to be completely elucidated, suggesting that the genetic burden is probably hidden in the form of a rare variant inside a family cluster or as an epigenetic factor that is responsible for regulating the expression of genes at the disease onset. In this doctoral thesis a large Romani family with an inherited form of multiple sclerosis has been studied clinically and genetically. The high number of affected members, the presence of several clinical forms and the ethnic characteristics of the family (with considerable inbreeding and a consequently high level of homozygosity) make it an exceptional, isolated population for the study of new genetic substrates associated with the disease. The results of this doctoral thesis reveal certain genetic variants, some of which have not been previously described, are significantly more frequent in the family members with MS than in unaffected subjects, suggesting that there are several candidate genes involved in the development of the disease in this particular familyLa esclerosis múltiple es una enfermedad crónica del sistema nervioso central, de etiología desconocida y mecanismo autoinmune en la que dos procesos patogénicos, la inflamación y la neurodegeneración, confluyen originando un trastorno de curso progresivo con un alto grado de discapacidad tanto física como cognitiva. Es la causa más frecuente de discapacidad neurológica de origen no traumático en la población adulta joven del mundo occidental. Estudios epidemiológicos y de historia natural demuestran que existe una susceptibilidad genética de base sobre la cual actuarían una serie de factores ambientales que generarían un desequilibrio del sistema inmune que producirá la afectación del sistema nervioso central con la consecuente manifestación de los signos y síntomas característicos de la enfermedad. Sin embargo, hasta ahora no se ha podido demostrar toda la heredabilidad que comporta la esclerosis múltiple lo cual nos indica que probablemente dicha carga genética se encuentra oculta en forma de una variante rara dentro de un clúster familiar o en forma de factores epigenéticos encargados de regular la expresión de los genes determinantes en la aparición de la enfermedad. Mediante este trabajo de tesis doctoral se ha estudiado, tanto clínicamente como genéticamente, a una extensa familia de etnia gitana con una forma hereditaria de esclerosis múltiple. El elevado número de miembros afectados, la presencia de varias formas clínicas y las características étnicas de la familia (una alta endogamia y, por tanto, una elevada homocigosis dentro de la misma), la convierten en una población aislada excepcional para el estudio de nuevos sustratos genéticos asociados a la enfermedad. Los resultados de esta tesis han permitido identificar ciertas variantes genéticas, algunas de ellas no descritas previamente, de forma significativamente más elevada entre los sujetos de la familia afectados de esclerosis múltiple en comparación a los no afectados, sugiriendo la existencia de varios genes candidatos implicados en el desarrollo de la enfermedad en esta familia concret

Identificación de genes de susceptibilidad en esclerosis múltiple. Descripción clínica y análisis genético de una extensa familia de etnia gitana (Estudio EMGypsy)

Multiple sclerosis is a chronic disease of the central nervous system which has an unknown aetiology and an autoimmune mechanism. Two pathogenic processes, inflammation and neurodegeneration, converge causing a progressive disorder with a high degree of both physical and cognitive disability. The disease is the most frequent cause of non-traumatic neurological disability in the young adult population in the Western world. Epidemiological and natural history studies show that there is a genetic susceptibility to the disease upon which a number of environmental factors act, generating an imbalance in the immune system that eventually produces a central nervous system attack with the consequent manifestation of the characteristic signs and symptoms of the disease. However, the inherited aspect of the disease has yet to be completely elucidated, suggesting that the genetic burden is probably hidden in the form of a rare variant inside a family cluster or as an epigenetic factor that is responsible for regulating the expression of genes at the disease onset. In this doctoral thesis a large Romani family with an inherited form of multiple sclerosis has been studied clinically and genetically. The high number of affected members, the presence of several clinical forms and the ethnic characteristics of the family (with considerable inbreeding and a consequently high level of homozygosity) make it an exceptional, isolated population for the study of new genetic substrates associated with the disease. The results of this doctoral thesis reveal certain genetic variants, some of which have not been previously described, are significantly more frequent in the family members with MS than in unaffected subjects, suggesting that there are several candidate genes involved in the development of the disease in this particular familyLa esclerosis múltiple es una enfermedad crónica del sistema nervioso central, de etiología desconocida y mecanismo autoinmune en la que dos procesos patogénicos, la inflamación y la neurodegeneración, confluyen originando un trastorno de curso progresivo con un alto grado de discapacidad tanto física como cognitiva. Es la causa más frecuente de discapacidad neurológica de origen no traumático en la población adulta joven del mundo occidental. Estudios epidemiológicos y de historia natural demuestran que existe una susceptibilidad genética de base sobre la cual actuarían una serie de factores ambientales que generarían un desequilibrio del sistema inmune que producirá la afectación del sistema nervioso central con la consecuente manifestación de los signos y síntomas característicos de la enfermedad. Sin embargo, hasta ahora no se ha podido demostrar toda la heredabilidad que comporta la esclerosis múltiple lo cual nos indica que probablemente dicha carga genética se encuentra oculta en forma de una variante rara dentro de un clúster familiar o en forma de factores epigenéticos encargados de regular la expresión de los genes determinantes en la aparición de la enfermedad. Mediante este trabajo de tesis doctoral se ha estudiado, tanto clínicamente como genéticamente, a una extensa familia de etnia gitana con una forma hereditaria de esclerosis múltiple. El elevado número de miembros afectados, la presencia de varias formas clínicas y las características étnicas de la familia (una alta endogamia y, por tanto, una elevada homocigosis dentro de la misma), la convierten en una población aislada excepcional para el estudio de nuevos sustratos genéticos asociados a la enfermedad. Los resultados de esta tesis han permitido identificar ciertas variantes genéticas, algunas de ellas no descritas previamente, de forma significativamente más elevada entre los sujetos de la familia afectados de esclerosis múltiple en comparación a los no afectados, sugiriendo la existencia de varios genes candidatos implicados en el desarrollo de la enfermedad en esta familia concret

CUIDADOS DE ENFERMERÍA EN HERIDAS QUIRÚRGICAS CONTAMINADAS EN EL HOSPITAL RODRÍGUEZ ZAMBRANO-MANTA Y VERDI CEVALLOS BALDA-PORTOVIEJO, 2015-2016.

CON ESTE ESTUDIO SE QUIERE BRINDAR A LOS PROFESIONALES DE SALUD EN GENERAL Y ESPECÍFICAMENTE A LOS QUE TRABAJAN EN FORMA DIRECTA CON EL PACIENTE, INFORMACIÓN SOBRE LA ATENCIÓN DE ENFERMERÍA, LA CALIDAD DE VIDA Y EL CUIDADO QUE SE DEBE BRINDAR, IDENTIFICANDO LAS REPERCUSIONES BIOLÓGICAS, PSICOLÓGICAS Y EMOCIONALES QUE SE PUEDEN PRESENTAR EN EL PACIENTE...LA PRESENTE INVESTIGACIÓN PRETENDE IDENTIFICAR EL NIVEL DE ATENCIÓN Y LA CALIDAD EN LA APLICACIÓN DE PROTOCOLOS ANTE LAS HERIDAS QUIRÚRGICAS CONTAMINADAS, PARA ASÍ FORTALECER DEBILIDADES LOGRANDO APLICAR CUIDADOS ÓPTIMOS EN BENEFICIO DE LA SALUD Y CORTA ESTANCIA DEL PACIENTE POS-QUIRÚRGICO..

CORRELACIÓN ETIOLÓGICA ENTRE LAS DISLIPEMIAS Y EL SÍNDROME VERTIGINOSO EN UNA MUESTRA DE 63 PACIENTES DEL SERVICIO DE NEUROLOGÍA DEL HOSPITAL DEL IESS DE MANTA DESDE ENERO A JUNIO DEL 2005.

PARA ESTE ESTUDIO FUERON SELECCIONADOS, DE FORMA ALEATORIA Y EN BASE A CRITERIOS DE INCLUSIÓN, 63 PACIENTES CON DIAGNÓSTICO CLÍNICO DE SÍNDROME VERTIGINOSO, ATENDIDOS EN EL SERVICIO DE NEUROLOGÍA DEL HOSPITAL DEL IESS DE MANTA DESDE ENERO A JUNIO DEL 2005, CON EL FIN DE CORRELACIONAR ETIOLÓGICAMENTE LAS DISLIPEMIAS CON SU SINTOMATOLOGÍA.FOR THIS STUDY WE SELECTED, IN A RANDOM WAY AND BASED ON INCLUSION APPROACHES, 63 PATIENTS WITH DIAGNOSTIC CLINICAL OF VERTIGINOUS SYNDROME, ASSISTED IN THE SERVICE OF NEUROLOGY OF THE HOSPITAL OF THE IESS-MANTA FROM JANUARY TO JUNE OF THE 2005, WITH THE PURPOSE OF ETIOLOGIC CORRELATING THE DYSLIPEMIAS WITH THEIR SINTOMATOLOGY

Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway Modulators, from Current Insights to Future Perspectives

Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are bioactive lipid molecules that are ubiquitously expressed in the human body and play an important role in the immune system. S1P-S1PR signaling has been well characterized in immune trafficking and activation in both innate and adaptive immune systems. Despite this knowledge, the full scope in the pathogenesis of autoimmune disorders is not well characterized yet. From the discovery of fingolimod, the first S1P modulator, until siponimod, the new molecule recently approved for the treatment of secondary progressive multiple sclerosis (SPMS), there has been a great advance in understanding the S1P functions and their involvement in immune diseases, including multiple sclerosis (MS). Modulation on S1P is an interesting target for the treatment of various autoimmune disorders. Improved understanding of the mechanism of action of fingolimod has allowed the development of the more selective second-generation S1PR modulators. Subtype 1 of the S1PR (S1PR1) is expressed on the cell surface of lymphocytes, which are known to play a major role in MS pathogenesis. The understanding of S1PR1’s role facilitated the development of pharmacological strategies directed to this target, and theoretically reduced the safety concerns derived from the use of fingolimod. A great advance in the MS treatment was achieved in March 2019 when the Food and Drug Association (FDA) approved Siponimod, for both active secondary progressive MS and relapsing–remitting MS. Siponimod became the first oral disease modifying therapy (DMT) specifically approved for active forms of secondary progressive MS. Additionally, for the treatment of relapsing forms of MS, ozanimod was approved by FDA in March 2020. Currently, there are ongoing trials focused on other new-generation S1PR1 modulators. This review approaches the fundamental aspects of the sphingosine phosphate modulators and their main similarities and differences

Differences in metacognition between multiple sclerosis phenotypes: cognitive impairment and fatigue are key factors

BackgroundCognitive impairment is present in 40–65% of patients with multiple sclerosis (pwMS). Objectively measured cognitive performance often does not match patients' subjective perception of their own performance.ObjectiveWe aimed to compare cognitive performance and subjective perception of cognitive deficits between pwMS and healthy controls (HCs), as well as the accuracy of subjective perception.MethodsIn total, 54 HC and 112 pwMS (relapsing–remitting, RRMS, and progressive PMS) underwent neuropsychological evaluation and completed perceived deficit, fatigue, and anxiety–depression scales. Participants were classified according to their consistency between subjective self-evaluation of cognitive abilities and objective cognitive performance to assess accuracy. Regression models were used to compare cognitive performance between groups and explore factors explaining inaccuracy in the estimation of cognitive performance.ResultsPMS showed greater and more widespread cognitive differences with HC than RRMS. No differences were found between pwMS and HC in the perception of deficit. PMS had higher ratios of overestimators. In explaining inaccuracy, fatigue and cognitive preservation were found to be risk factors for underestimation, whereas physical disability and cognitive impairment were risk factors for overestimation.ConclusionPwMS have metacognitive knowledge impairments. This study provides new information about metacognition, data on the prevalence of impairments over a relatively large sample of PwMS, and new insights into factors explaining it. Anosognosia, related to cognitive impairment, may be present in pwMS. Fatigue is a key factor in underestimating cognition

Description of a CSF-Enriched miRNA Panel for the Study of Neurological Diseases

Background: The study of circulating miRNAs in CSF has gained tremendous attention during the last years, as these molecules might be promising candidates to be used as biomarkers and provide new insights into the disease pathology of neurological disorders. Objective: The main aim of this study was to describe an OpenArray panel of CSF-enriched miRNAs to offer a suitable tool to identify and characterize new molecular signatures in different neurological diseases. Methods: Two hundred and fifteen human miRNAs were selected to be included in the panel, and their expression and abundance in CSF samples were analyzed. In addition, their stability was studied in order to propose suitable endogenous controls for CSF miRNA studies. Results: miR-143-3p and miR-23a-3p were detected in all CSF samples, while another 80 miRNAs were detected in at least 70% of samples. miR-770-5p was the most abundant miRNA in CSF, presenting the lowest mean Cq value. In addition, miR-26b-5p, miR-335-5p and miR-92b-3p were the most stable miRNAs and could be suitable endogenous normalizers for CSF miRNA studies. Conclusions: These OpenArray plates might be a suitable and efficient tool to identify and characterize new molecular signatures in different neurological diseases and would improve the yield of miRNA detection in CSF

Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates

BACKGROUND: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. OBJECTIVES: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. METHODS: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006-1 January 2016 and prevalence for the date 1 January 2016. RESULTS: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10-76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5-fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40-59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. CONCLUSION: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification