Deterioro cognitivo en pacientes con esclerosis múltiple / Cognitive impairment in patients with multiple sclerosis

La esclerosis múltiple es una enfermedad inflamatoria, autoinmune y neurodegenerativa del sistema nervioso central caracterizada por pérdida de la función motora y sensitiva; es considerada una de las principales causas de discapacidad en el adulto joven. Recientemente, se le ha dado gran importancia al deterioro cognitivo, por ser un síntoma frecuente y discapacitante. Este deterioro está presente en un 40 a 65% de los pacientes y afecta la velocidad de procesamiento de información, atención compleja, memoria de trabajo, memoria visual y verbal, fluencia verbal y funciones ejecutivas. Se puede presentar en el síndrome radiológico aislado, en el síndrome clínico aislado y en las diferentes fases de la enfermedad; además, es el responsable de la dependencia de algunos pacientes y de las dificultades para mantener o conseguir empleo. Este déficit cognitivo se asocia a atrofia del tálamo y se ha observado una correlación con las medidas de atrofia y con el volumen lesional cerebral. Existen diferentes herramientas para su evaluación; hay pruebas de cribado breves de 5 minutos de duración, hasta baterías extensas de 90 minutos. Respecto al tratamiento de las alteraciones cognitivas, no existe un tratamiento farmacológico específico; sin embargo, se considera que los fármacos modificadores de la enfermedad podrían tener una influencia favorable en la función cognitiva por sus efectos en la reducción de la actividad inflamatoria y la atrofia cerebral. En cuanto a la estimulación cognitiva, no existen datos concluyentes por las diferentes técnicas empleadas y las distintas medidas utilizadas para evaluar los resultados de las intervenciones.

Multiple sclerosis is an inflammatory, autoimmune and neurodegenerative central nervous system disease characterized by motor and sensitive function loss; it is considered to be one of the principal causes of disability in young adults. Recently, cognitive impairment has gain considerable attention because it is a frequent symptom that causes disability. Cognitive impairment it is present in 40 to 65% of patients and affectsspeed of information processing, complex attention, working memory, visual and verbal memory, verbal fluency and executive functions. It may be present in radiologically isolated syndrome, clinically isolated síndrome and in the different stages of the disease; it is responsible for patient’s dependence and for the difficulties to maintain or get an employment. Cognitive impairment is associated to thalamic atrophy and a correlation with brain atrophy and cerebral lesional volume has been observed. Different evaluation tools are available, there are 5 minutes short screening tests and comprehensive 90 minutes batteries. Regarding cognitive impairment treatment, there is not a specific pharmacological treatment, nevertheless, disease modifying therapies could have a favorable influence on cognitive function because of their effects in the reduction of inflammatory activity and brain atrophy. There are no conclusive data about the efficacy of cognitive stimulation because of the diverse techniques employed and the different measures used to evaluate the results of the interventions.

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review.

INTRODUCTION: Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS. METHODS: Serum samples from patients with MS (n = 108) and controls (n = 77) were tested for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with the low-glycosylated fraction of recombinant KIR4.1 purified from transfected HEK293 cells according to original protocols; 2) by immunocytochemistry using KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.-transfected MO3.13 oligodendrocyte cell line. We developed a systematic review and meta-analysis of the association of anti-KIR4.1 antibodies with MS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: We did not detect anti-KIR4.1 antibodies in the MS patients or in controls using ELISA. Neither did we detect any significant reactivity against the antigen on the cell surface using the KIR4.1-transfected HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective controlled studies in the systematic review. Only three studies showed a positive association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity between studies precluded meta-analysis of their results. CONCLUSION: We found no association between anti-KIR4.1 antibody positivity and MS. Although this lack of replication may be due to technical limitations, evidence from our study and others is mounting against the role of KIR4.1 as a relevant MS autoantigen.

Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes.

A one-year follow-up study of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) in relapsing-remitting multiple sclerosis: an appraisal of comparative longitudinal sensitivity.

BACKGROUND: Neuropsychological batteries are infrequently used to assess cognitive impairment in multiple sclerosis because they are time-consuming and require trained personnel. The Symbol Digit Modalities Test (SDMT) is suggested to be a useful screening tool to measure cognitive impairment in multiple sclerosis patients and is more valid and reliable over time than the Paced Auditory Serial Addition Test (PASAT). The purpose of this study was to evaluate which of these tests was more sensitive to cognitive impairment at one-year follow-up. METHODS: A total of 237 patients with relapsing-remitting multiple sclerosis and 57 healthy controls underwent a complete neuropsychological assessment. One year later, we assessed 196 patients using the Brief Repeatable Battery of Neuropsychological Tests. We also administered other executive function and prospective memory tests, together with fatigue and depression questionnaires. RESULTS: A total of 33.8% of patients were classified as cognitively impaired. The SDMT and the PASAT 3 seconds test (PASAT3) had a sensitivity of 0.809 and 0.783, respectively, thereby classifying patients as cognitively impaired. Analysis of 196 patients one year later showed 31.6% had cognitive impairment compared with 27.6% at the first assessment. The sensitivity to detect cognitive impairment after one year was 0.824 for SDMT and 0.796 for PASAT3. When the predictors were removed from the comparative standard battery, SDMT still showed a slightly higher sensitivity. Both SDMT and PASAT3 correlated significantly with all tests, but SDMT showed higher correlation values. Furthermore, SDMT was completed by all subjects while PASAT3 was completed by 86.9% of patients and 94.7% of controls. CONCLUSIONS: SDMT is simpler to administer than PASAT3 and may be slightly more sensitive to MS cognitive impairment. It could thus be a suitable test to assess cognitive impairment routinely in people with relapsing-remitting multiple sclerosis.

Effect of levetiracetam on cognitive functions and quality of life: a one-year follow-up study.

PURPOSE: The purpose of the study was to assess changes in cognitive functions and quality of life in patients with epilepsy over one year of treatment with levetiracetam (LEV) as add-on therapy. METHODS: Thirty-two patients (16 women; 16 men) who received LEV as an add-on treatment were included, and 27 completed the one-year follow-up period. Extensive neuropsychological assessments, together with a quality-of-life questionnaire were administered at baseline and at one, three, six and twelve months after beginning the add-on treatment. Patients received LEV starting with 500 mg/day in the first week, increasing by a further 500 mg/day per week until a target dose of 2 000 mg/day was reached by the end of the first month. RESULTS: At the one-year follow-up, a significant improvement was observed in measurements of prospective memory, working memory, motor functions, verbal fluency, attention and quality of life. Performance for neuropsychological and quality-of-life tests was not affected by external variables such as seizure reduction or changes in previous anti-epileptic treatment. Slight changes between patients were observed, but these were not clinically significant.The limited sample size and the lack of a control group should be mentioned as limitations of the study. No control group was evaluated as in our clinical practice it was difficult to establish a comparable group of patients. Changes in the different variables were assessed by comparing baseline information with follow-up results.Despite the study limitations, we consider that the one-year treatment period provides valuable information regarding the drug's long-term effects in this setting. CONCLUSIONS: Results of the present study suggest that long-term LEV treatment as add-on therapy does not interfere with cognitive function and improves quality of life.