XIII Reunión Post-ECTRIMS : revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I)

Introducción: Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo: En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo. En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones: Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.Introduction. For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). Aim. This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. Development. This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. Conclusions. There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS

Atlas de las praderas marinas de España

Knowledge of the distribution and extent of seagrass habitats is currently the basis of management and conservation policies of the coastal zones in most European countries. This basic information is being requested through European directives for the establishment of monitoring programmes and the implementation of specific actions to preserve the marine environment. In addition, this information is crucial for the quantification of the ecological importance usually attributed to seagrass habitats due to, for instance, their involvement in biogeochemical cycles, marine biodiversity and quality of coastal waters or global carbon budgets. The seagrass atlas of Spain represents a huge collective effort performed by 84 authors across 30 Spanish institutions largely involved in the scientific research, management and conservation of seagrass habitats during the last three decades. They have contributed to the availability of the most precise and realistic seagrass maps for each region of the Spanish coast which have been integrated in a GIS to obtain the distribution and area of each seagrass species. Most of this information has independently originated at a regional level by regional governments, universities and public research organisations, which explain the elevated heterogeneity in criteria, scales, methods and objectives of the available information. On this basis, seagrass habitats in Spain occupy a total surface of 1,541,63 km2, 89% of which is concentrated in the Mediterranean regions; the rest is present in sheltered estuarine areas of the Atlantic peninsular regions and in the open coastal waters of the Canary Islands, which represents 50% of the Atlantic meadows. Of this surface, 71.5% corresponds to Posidonia oceanica, 19.5% to Cymodocea nodosa, 3.1% to Zostera noltii (=Nanozostera noltii), 0.3% to Zostera marina and 1.2% to Halophila decipiens. Species distribution maps are presented (including Ruppia spp.), together with maps of the main impacts and pressures that has affected or threatened their conservation status, as well as the management tools established for their protection and conservation. Despite this considerable effort, and the fact that Spain has mapped wide shelf areas, the information available is still incomplete and with weak precision in many regions, which will require an investment of major effort in the near future to complete the whole picture and respond to demands of EU directives

Comparative effectiveness of autologous hematopoietic stem cell transplant vs fingolimod, natalizumab, and ocrelizumab in highly active relapsing-remitting multiple sclerosis

Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time

Atlas de las praderas marinas de España

Knowledge of the distribution and extent of seagrass habitats is currently the basis of management and conservation policies of the coastal zones in most European countries. This basic information is being requested through European directives for the establishment of monitoring programmes and the implementation of specific actions to preserve the marine environment. In addition, this information is crucial for the quantification of the ecological importance usually attributed to seagrass habitats due to, for instance, their involvement in biogeochemical cycles, marine biodiversity and quality of coastal waters or global carbon budgets. The seagrass atlas of Spain represents a huge collective effort performed by 84 authors across 30 Spanish institutions largely involved in the scientific research, management and conservation of seagrass habitats during the last three decades. They have contributed to the availability of the most precise and realistic seagrass maps for each region of the Spanish coast which have been integrated in a GIS to obtain the distribution and area of each seagrass species. Most of this information has independently originated at a regional level by regional governments, universities and public research organisations, which explain the elevated heterogeneity in criteria, scales, methods and objectives of the available information. On this basis, seagrass habitats in Spain occupy a total surface of 1,541,63 km2, 89% of which is concentrated in the Mediterranean regions; the rest is present in sheltered estuarine areas of the Atlantic peninsular regions and in the open coastal waters of the Canary Islands, which represents 50% of the Atlantic meadows. Of this surface, 71.5% corresponds to Posidonia oceanica, 19.5% to Cymodocea nodosa, 3.1% to Zostera noltii (=Nanozostera noltii), 0.3% to Zostera marina and 1.2% to Halophila decipiens. Species distribution maps are presented (including Ruppia spp.), together with maps of the main impacts and pressures that has affected or threatened their conservation status, as well as the management tools established for their protection and conservation. Despite this considerable effort, and the fact that Spain has mapped wide shelf areas, the information available is still incomplete and with weak precision in many regions, which will require an investment of major effort in the near future to complete the whole picture and respond to demands of EU directives.Versión del edito

Whole-transcriptome analysis in peripheral blood mononuclear cells from patients with lipid-specific oligoclonal IgM band characterization reveals two circular RNAs and two linear RNAs as biomarkers of highly active disease

The presence of anti-myelin lipid-specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal fluid, a quite invasive liquid biopsy. In the present study we aimed at studying the expression profile of miRNA, snoRNA, circRNA and linearRNA in peripheral blood mononuclear cells (PBMCs) from patients with lipid-specific oligoclonal IgM band characterization. We included a total of 89 MS patients, 47 with negative LS-OCMB status and 42 with positive status. Microarray (miRNA and snoRNA) and RNA-seq (circular and linear RNAs) were used to perform the profiling study in the discovery cohort and candidates were validated by RT-qPCR in the whole cohort. The biomarker potential of the candidates was evaluated by ROC curve analysis. RNA-seq and RT-qPCR validation revealed that two circular (hsa_circ_0000478 and hsa_circ_0116639) and two linear RNAs (IRF5 and MTRNR2L8) are downregulated in PBMCs from patients with positive LS-OCMBs. Finally, those RNAs show a performance of a 70% accuracy in some of the combinations. The expression of hsa_circ_0000478, hsa_circ_0116639, IRF5 and MTRNR2L8 might serve as minimally invasive biomarkers of highly active disease

Whole-transcriptome analysis in peripheral blood mononuclear cells from patients with lipid-specific oligoclonal IgM band characterization reveals two circular RNAs and two linear RNAs as biomarkers of highly active disease

The presence of anti-myelin lipid-specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal fluid, a quite invasive liquid biopsy. In the present study we aimed at studying the expression profile of miRNA, snoRNA, circRNA and linearRNA in peripheral blood mononuclear cells (PBMCs) from patients with lipid-specific oligoclonal IgM band characterization. We included a total of 89 MS patients, 47 with negative LS-OCMB status and 42 with positive status. Microarray (miRNA and snoRNA) and RNA-seq (circular and linear RNAs) were used to perform the profiling study in the discovery cohort and candidates were validated by RT-qPCR in the whole cohort. The biomarker potential of the candidates was evaluated by ROC curve analysis. RNA-seq and RT-qPCR validation revealed that two circular (hsa_circ_0000478 and hsa_circ_0116639) and two linear RNAs (IRF5 and MTRNR2L8) are downregulated in PBMCs from patients with positive LS-OCMBs. Finally, those RNAs show a performance of a 70% accuracy in some of the combinations. The expression of hsa_circ_0000478, hsa_circ_0116639, IRF5 and MTRNR2L8 might serve as minimally invasive biomarkers of highly active disease

Confirmed disability progression as a marker of permanent disability in multiple sclerosis

Background and purpose The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29–0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score ˃1.5). Conclusions Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual