Esclerosis múltiple familiar: características diferenciales respecto a la forma esporádica.

Los estudios con pacientes con formas familiares de la enfermedad son necesarios para profundizar en el conocimiento de los mecanismos etiopatogénicos de la EM. Existen numerosos estudios que estudian la prevalencia y el riesgo de tener EM en las formas familiares, pero son pocos los que analizan las características epidemiológicas y las características clínicas de la propia enfermedad en estas formas y las comparen con las formas no familiares o esporádicas. Proponemos un estudio con una gran población de pacientes de diversas nacionalidades y razas, que nos aportará información sobre cómo se comportan las formas familiares de EM y nos ayudará a tomar decisiones adecuadas con nuestros pacientes en cuanto a su tratamiento y seguimiento. • OBJETIVO PRINCIPAL: Comparar características epidemiológicas y clínicas de la esclerosis múltiple comparando entre las formas familiares y las esporádicas. • MATERIAL Y MÉTODOS: Los pacientes de este estudio, están en seguimiento en diferentes centros especializados en Esclerosis Múltiple. son evaluados por un neurólogo cualificado y especializado en EM al menos cada 6 meses y cada vez que se sospeche un brote de la enfermedad. Se utilizó la base de datos MSBASE (MS Base International Registry) (www.msbase.org) para registrar y hacer un seguimiento prospectivo de los pacientes. Se recogen datos de pacientes de MSBASE desde el 15 de Enero de 2005 hasta el 14 de Abril de 2016. • RESULTADOS: Analizamos 17.739 pacientes diagnosticados de Esclerosis Múltiple, de ellos 1194 tenían uno o más familiares diagnosticados de EM y 16.454 presentaban una EM esporádica. La prevalencia de EM familiar en nuestra cohorte es del 7.25%. Encontramos diferencias en el curso clínico de la enfermedad entre pacientes con una EMF y una esclerosis múltiple esporádica. El inicio de la enfermedad en formas familiares es más temprano, con menor frecuencia de brote visual con debut, los pacientes tienen antes el segundo brote, mayor numero de brotes en los 5 primeros años y tardan menos años en desarrollar una fase progresiva de la enfermedad. No encontramos diferencias en estas características según el grado de parentesco en las formas familiares. • CONCLUSIONES: Con este estudio aportamos la mayor muestra internacional de pacientes con EMF hasta ahora publicada y los primeros resultados que confirman que el curso clínico de los pacientes con EMF es diferente a la forma esporádica. Todos nuestros resultados apuntan a que el curso evolutivo de la EMF es más agresivo y con un peor pronóstico que las formas esporádicas. Estos resultados podrían cambiar el manejo terapéutico de los pacientes con una esclerosis múltiple familiar y así, utilizar en ellos tratamientos de mayor eficacia que en pacientes con una esclerosis múltiple esporádica

Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years

Alemtuzumab; Efficacy; SafetyAlemtuzumab; Eficacia; SeguridadAlemtuzumab; Eficàcia; SeguretatBackground Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]). Methods Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years). Results Compared with SC IFNB-1a over 2 years across age cohorts, alemtuzumab lowered annualized relapse rates (ARR; 0.22–0.24 vs. 0.38–0.51), improved or stabilized disability (freedom from 6-month confirmed disability worsening [CDW]: 85%–92% vs. 62%–88%; achievement of 6-month confirmed disability improvement [CDI]: 20%–31% vs. 13%–25%), increased proportions free of MRI disease activity (70%–86% vs. 42%–63% per year), and slowed brain volume loss (BVL; –0.45% to –0.87% vs. –0.50% to –1.39%). Through Year 2, the treatment effect with alemtuzumab did not significantly differ among age groups for ARR (p-interaction=0.6325), 6-month CDW-free (p-interaction=0.4959), 6-month CDI (p-interaction=0.9268), MRI disease activity-free (p-interaction=0.6512), and BVL (p-interaction=0.4970). Alemtuzumab remained effective on outcomes through Year 8 across age groups. Age-related increases in malignancies (≤45 years: 0.9%–2.2% vs. >45 years: 8.1%) and deaths (0%–1.7% vs. 7.0%) were observed. Serious infections also increased from the youngest (5.1%) to oldest (12.8%) age cohorts. Conclusions Alemtuzumab had greater efficacy than SC IFNB-1a over 2 years across comparable age groups, with no significant differences between alemtuzumab-treated age groups. Efficacy on relapse, disability, and MRI outcomes continued through Year 8 across age groups. Age-related increases in serious infections, malignancies, and deaths were observed.The study was supported by Sanofi and Bayer HealthCare Pharmaceuticals

Consensus on early detection of disease progression in patients with multiple sclerosis

Consensus; Early detection; Secondary progressive multiple sclerosisConsenso; Detección precoz; Esclerosis múltiple progresiva secundariaConsens; Detecció precoç; Esclerosi múltiple progressiva secundàriaBackground: Early identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) can be challenging for clinicians, as diagnostic criteria for SPMS are primarily based on physical disability and a holistic interpretation. Objective: To establish a consensus on patient monitoring to identify promptly disease progression and the most useful clinical and paraclinical variables for early identification of disease progression in MS. Methods: A RAND/UCLA Appropriateness Method was used to establish the level of agreement among a panel of 15 medical experts in MS. Eighty-three items were circulated to the experts for confidential rating of the grade of agreement and recommendation. Consensus was defined when ≥66% agreement or disagreement was achieved. Results: Consensus was reached in 72 out of 83 items (86.7%). The items addressed frequency of follow-up visits, definition of progression, identification of clinical, cognitive, and radiological assessments as variables of suspected or confirmed SPMS diagnosis, the need for more accurate assessment tools, and the use of promising molecular and imaging biomarkers to predict disease progression and/or diagnose SPMS. Conclusion: Consensus achieved on these topics could guide neurologists to identify earlier disease progression and to plan targeted clinical and therapeutic interventions during the earliest stages of SPMS.This work was supported by Novartis. Meetings, data analysis, and medical writing assistance were funded by Novartis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Deciphering Multiple Sclerosis Progression

Esclerosi múltiple; NeurodegeneracióEsclerosis múltiple; NeurodegeneraciónMultiple sclerosis; NneurodegenerationMultiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0–5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches

Usefulness of optic nerve ultrasound to predict clinical progression in multiple sclerosis

Introducción La pérdida neuronal/axonal progresiva se considera la causa más importante de discapacidad neurológica en la esclerosis múltiple (EM). El sistema visual está frecuentemente afectado en esta enfermedad y su accesibilidad a test funcionales y estructurales ha permitido que se convierta en un modelo para estudiar in vivo la patogenia de la EM. La ecografía orbitaria permite evaluar, de forma no invasiva y en tiempo real, las diversas estructuras de la órbita, incluido el nervio óptico. Material y métodos Se ha llevado a cabo un estudio observacional ambispectivo en pacientes con EM recogiéndose datos evolutivos de la enfermedad. La ecografía orbitaria se realizó en todos los pacientes según el principio de mínima potencia necesaria (ALARA). También se recogieron los datos de tomografía de coherencia óptica (OCT) en aquellos que tenían realizadas ambas pruebas. El estudio estadístico se efectuó con el programa SPSS 22.0. Resultados Se encontraron correlaciones estadísticamente significativas entre las medidas ecográficas y la progresión de la enfermedad (p = 0,041 para el ojo derecho y p = 0,037 para el ojo izquierdo), y la Expanded Disability Status Scale (EDSS) final en el seguimiento (p = 0,07 para el ojo derecho y p = 0,043 para el ojo izquierdo). No fue así para los datos referentes a brotes y a otras variables clínicas. Discusión La medición del diámetro del nervio óptico por ecografía podría utilizarse como medida predictiva en la evolución de la EM, ya que la disminución del mismo se asocia con progresión clínica y mayor discapacidad, medidas con la EDSS.Introduction Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. Material and methods We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the ‘as low as reasonably achievable’ (ALARA) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. Results Disease progression was significantly correlated with ultrasound findings (P = .041 for the right eye and P = .037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P = .07 for the right eye and P = .043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. Discussion Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS)

Gender Gap in the Leadership of Health Institutions: The Influence of Hospital-Level Factors.

Objective: To analyze whether the increased representation of women in the health field is accompanied by a greater presence in leadership positions in the public health system and whether there are differences according to the hospital level. Methods: A descriptive study of the distribution of leadership positions by sex and type of hospital within the health centers of a regional public health system. Results: In total, 74.01% of the professionals were women. The representation of women in management positions was 33.1%, and among service chiefs, it was 24.01%. In the service headings, we observed that surgical specialties had a lower representation of women (30.9% in medical specialties vs. 18.1% in surgical specialties,

Deficits in Early Sensory and Cognitive Processing Are Related to Phase and Nonphase EEG Activity in Multiple Sclerosis Patients

Currently, there is scarce knowledge about the relation between spectral bands modulations and the basis of cognitive impairment in multiple sclerosis (MS). In this sense, analyzing the evoked or phase activity can confirm results from traditional event-related potential (ERP) studies. However, studying the induced or nonphase activity may be necessary to elucidate hidden compensatory or affected cognitive mechanisms. In this study, 30 remitting-relapsing multiple sclerosis patients and 30 healthy controls (HCs) matched in sociodemographic variables performed a visual oddball task. The main goal was to analyze phase and nonphase alpha and gamma bands by applying temporal spectral evolution (TSE) and its potential relation with cognitive impairment in these patients. The behavioural results showed slower reaction time and poorer accuracy in MS patients compared to controls. In contrast, the time-frequency analysis of electroencephalography (EEG) revealed a delay in latency and lower amplitude in MS patients in evoked and induced alpha compared to controls. With respect to the gamma band, there were no differences between the groups. In summary, MS patients showed deficits in early sensorial (evoked alpha activity) and cognitive processing (induced alpha activity in longer latencies), whereas the induced gamma band supported the hypothesis of its role in translation of attentional focus (induced activity) and did not show strong activity in this paradigm (visual oddball).Ministerio de Economía y Competitividad de España PSI2016- 78133-

Efficacy of diet on fatigue, quality of life and disability status in multiple sclerosis patients: rapid review and meta-analysis of randomized controlled trials.

Multiple sclerosis is an inflammatory and neurodegenerative disease. People with multiple sclerosis (pwMS) experience chronic fatigue which is difficult to deal with therapeutically and greatly affects health-related quality of life (QOL). PwMS are aware of the lack of generalized dietary advice related to their disease, leading to self-experimentation with diet. It is necessary to provide objective information about dietary interventions for pwMS. We aim to provide an objective synthesis of the evidence for efficacy and safety of specific diets in pwMS through a rapid review and meta-analyses of randomized controlled trials (RCTs), examining symptomatic fatigue (MFIS), QOL, Expanded-Disability-Status-Scale (EDSS), and severe adverse events. We have carried out a rapid review (MEDLINE and EMBASE) up to December 2021, with PRISMA methodology, and meta-analyses, of (RCTs). All statistical analyses were performed using the comprehensive meta-analysis (CMA) -RStudio 4.1.3. The analysis used weighted mean differences (WMD) and a 95% confidence interval (CI) using a random-effects model to compare the effects of the dietary intervention with the control. Eight studies met the inclusion criteria. Of these eight studies, five analyzed EDSS, three MFIS, and three QOL. A total of 515 patients were analyzed. These meta-analyses cumulative evidence support that dietary intervention is associated with a trend of reduction in fatigue (308 patients studied) -the difference between means (SMD) of the control group and intervention group was -2,033, 95%-IC (-3,195, -0,152), a p-value of 0.0341)-, an increase in QOL (77 patients studied), no significant effect on EDSS (337 patients studied), and no severe adverse events. It is difficult to reach a high level of evidence in dietary studies. Our findings show that dietary intervention is associated with a trend of reduction in fatigue in MS. Taking into account the potential of dietary interventions and the benefit/risk ratio in their favor, neurologists must be aware of the great importance of making interventions on diet in MS if necessary. There are dietary interventions with some evidence of benefit for patients with MS, which could be chosen based on adherence, patient preferences, and individual outcomes. Large prospective clinical trials are needed to shed further light on this topic

Deciphering Multiple Sclerosis Progression.

Multiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0-5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches