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Background The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. Methods A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. Results A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach’s alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken’s criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). Conclusions The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD.

For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS.This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020.This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed.Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS.XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II).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) se reúnen para revisar las novedades presentadas en el ECTRIMS. Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias de la reunión post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 virtualmente. Desarrollo. En esta segunda parte se destaca la importancia del género y la edad en la compresión de la patología de la enfermedad y la optimización de su manejo. Se exponen los avances realizados en la EM pediátrica desde un punto de vista neuropsicológico y de neuroimagen. Por su parte, cobran especial protagonismo los hallazgos que contribuyen a realizar un enfoque del tratamiento más personalizado y a elegir la mejor estrategia de tratamiento (farmacológica y no farmacológica) para cada paciente. De igual forma, se abordan los resultados relacionados con las estrategias posibles que promuevan la remielinización. Aunque no hay grandes avances en el tratamiento de formas progresivas, se destacan algunos métodos cuantitativos para la clasificación de estos pacientes. Además, se incluyen los resultados sobre herramientas potenciales de evaluación y tratamiento de los déficits cognitivos, y algunos aspectos relevantes observados en el espectro de los trastornos de la neuromielitis óptica. Por último, se detallan los resultados de las ponencias consideradas como noticias de última hora en el ECTRIMS-ACTRIMS. Conclusiones. Se presentaron avances principalmente sobre el conocimiento de la EM pediátrica, las estrategias de remielinización y la evaluación cognitiva en la EM.

Jose E Meca-Lallana,1 Daniel Prefasi,2 Francisco Pérez-Miralles,3 Lucía Forero,4 María Sepúlveda,5 Carmen Calles,6 María L Martínez-Ginés,7 Inés González-Suárez,8 Sabas Boyero,9 Lucía Romero-Pinel,10 Ángel P Sempere,11 Virginia Meca-Lallana,12 Luis Querol,13 Lucienne Costa-Frossard,14 Hugo de Castro-Trapiello,2 Neus Canal,15 Jorge Maurino2 1Clinical Neuroimmunology Unit and Multiple Sclerosis CSUR. Department of Neurology. Hospital Universitario “Virgen de la Arrixaca”, IMIB-Arrixaca, Murcia, Spain; 2Medical Department, Roche Farma, Madrid, Spain; 3Unit of Neuroimmunology, Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 4Department of Neurology, Hospital Universitario Puerta del Mar, Cádiz, Spain; 5Department of Neurology, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain; 6Department of Neurology, Hospital Universitari Son Espases, Palma de Mallorca, Spain; 7Department of Neurology, Hospital Universitario Gregorio Marañón, Madrid, Spain; 8Department of Neurology, Hospital Universitario Álvaro Cunqueiro, Vigo, Spain; 9Department of Neurology, Hospital Universitario Cruces, Bilbao, Spain; 10Department of Neurology, Hospital Universitari de Bellvitge, Barcelona, Spain; 11Department of Neurology, Hospital General Universitario de Alicante, Alicante, Spain; 12Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain; 13Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 14Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain; 15Department of Statistics, IQVIA, Barcelona, SpainCorrespondence: Jorge MaurinoRoche Farma, Ribera Del Loira, 50, Madrid, 28042, SpainTel +34 913 24 81 00Email jorge.maurino@roche.comBackground: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD).Methods: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman’s rank correlation.Results: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p< 0.0001) and psychological (rho=0.608, p< 0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p< 0.0001), MOS-PES score (rho= 0.457, p< 0.0001), and D-FIS score (rho=0.556, p< 0.0001).Conclusion: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge.Keywords: neuromyelitis optica spectrum disorder, stigma, quality of life, depression, patient-reported outcomes

Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting.To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts.In this second part, the most recent evidence on the use of disease-modifying treatments during pregnancy is presented. Details are provided concerning the results of phase 3 clinical trials conducted to evaluate the efficacy and safety of two potential disease-modifying treatments for relapsing-remitting multiple sclerosis: ponesimod and ofatumumab. For the progressive forms, both available disease modifying treatments and others still in the research phase are reviewed. In the field of stem cell therapies, the article includes the results of the only clinical trial carried out to date comparing patients with relapsing-remitting multiple sclerosis treated with autologous haematopoietic stem cell transplantation and those treated with disease-modifying therapies. There are no important developments as regards symptomatic treatments, although the European Academy of Neurology has published a guide on palliative care. The various sources of information that collect pharmacovigilance data in the post-marketing setting are reviewed.Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available.XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (II).Introducción. Como cada año, tras la celebración del Congreso del ECTRIMS, reconocidos neurólogos españoles expertos en esclerosis múltiple expusieron en la Reunión Post-ECTRIMS las principales novedades en investigación en este ámbito. Objetivo. Sintetizar el contenido presentado en la XII edición de la Reunión Post-ECTRIMS, que tuvo lugar en septiembre de 2019 en Sevilla y que se presenta en dos partes. Desarrollo. En esta segunda parte, se exponen las evidencias más recientes sobre el uso de tratamientos modificadores de la enfermedad durante el embarazo. Se detallan los resultados de ensayos clínicos en fase 3 en los que se ha evaluado la eficacia y la seguridad de dos potenciales tratamientos modificadores de la enfermedad para la esclerosis múltiple remitente recurrente: ponesimod y ofatumumab. Para las formas progresivas, se revisan los tratamientos modificadores de la enfermedad disponibles y en investigación. En el ámbito de las terapias con células madre, se incluyen los resultados del único ensayo clínico hasta la fecha que compara a pacientes con esclerosis múltiple remitente recurrente tratados con trasplante autólogo de células madre hematopoyéticas y a los tratados con tratamientos modificadores de la enfermedad. No hay grandes novedades sobre tratamientos sintomáticos, aunque la Academia Europea de Neurología ha publicado una guía sobre cuidados paliativos. Se revisan las distintas fuentes de información que recogen datos de farmacovigilancia en el entorno poscomercialización. Conclusiones. Los pacientes diagnosticados en los últimos años tienden a tener una menor gravedad de la esclerosis múltiple, probablemente debido al diagnóstico desde sus estadios más leves y al continuo aumento de tratamientos disponibles.

The Post-ECTRIMS Meeting is an emblematic event in Spain which seeks to review and disseminate the main advances in multiple sclerosis presented at the ECTRIMS annual congress. In October 2018, the eleventh Post-ECTRIMS meeting was held in Madrid and was attended by the country's leading experts in multiple sclerosis. As a result of this meeting, we present two articles which outline the most interesting novelties discussed there. This first part includes the latest results obtained regarding the influence of modifiable and non-modifiable risk factors in multiple sclerosis, with emphasis on the progress made in the field of genetics, where the discovery of genes associated with multiple sclerosis has increased exponentially. The complexity of the immune system is addressed and some contributions are made on autoimmunity mechanisms, in which bidirectional relations are observed between immune cells and cells residing in the central nervous system, such as microglial cells and astrocytes. Biomarkers, both in serum and cerebrospinal fluid as well as in imaging, are gaining more and more attention due to their current and, above all, potential role in the diagnosis and prognosis of the disease and in the evaluation of the efficacy of treatments. Finally, the observations made regarding changes in structural and functional connectivity in patients and their relationship with clinical alterations are presented.Revision de las novedades presentadas en el congreso ECTRIMS 2018: XI Reunion Post-ECTRIMS (I).La reunion Post-ECTRIMS es un encuentro emblematico en Espana que persigue revisar y difundir los principales avances en esclerosis multiple presentados en el congreso anual ECTRIMS. En octubre de 2018, la reunion Post-ECTRIMS celebro en Madrid su undecima edicion, contando con los mayores expertos de ambito nacional en esclerosis multiple. Como resultado de esta reunion, se presentan dos articulos donde se recogen las novedades mas destacadas en la misma. En esta primera parte se incluyen los ultimos resultados sobre la influencia de los factores de riesgo modificables y no modificables en la esclerosis multiple, destacando los progresos realizados en el ambito genetico, donde el descubrimiento de genes asociados a la esclerosis multiple ha aumentado exponencialmente. Se aborda la complejidad del sistema inmune y se realizan algunas aportaciones sobre los mecanismos de autoinmunidad, en los que se observan relaciones bidireccionales entre las celulas inmunes y las celulas residentes del sistema nervioso central, como la microglia y los astrocitos. Los biomarcadores, tanto en suero y liquido cefalorraquideo como de imagen, ganan cada vez mas atencion por su papel actual, y sobre todo potencial, en el diagnostico y pronostico de la enfermedad y en la evaluacion de la eficacia de los tratamientos. Por ultimo, se presentan las observaciones realizadas respecto a los cambios en la conectividad estructural y funcional en los pacientes y su relacion con las alteraciones clinicas.

Cell-adhesion molecules (CAMs) dynamics in Multiple Sclerosis (MS) patients have been widely studied after Natalizumab (NTZ) introduction. However, their temporal dynamics after NTZ withdrawal (NTZ-W) has not been described. We prospectively evaluate changes in the expression levels of CAMs (CD49d, CD29, L-Selectin and CD11a) involved in T cell migration of 22 MS patients after NTZ-W. CD49d, CD29 and CD11a expression experienced a continuous increase expression two months after NTZ-W and Cd49d expression at month six after NTZ-W correlated to NTZ treatment duration, both in CD45+CD4+ and CD45+CD8+. CD49d expression up to month three after NTZ-W was related to MS activity in CD45+CD8+ at the end of the study. Results from this study suggest that patients with a longer NTZ treatment are more susceptible to present a "molecular rebound" after NTZ-W. CD49d determination may be a useful tool to closely monitor MS activity in patients who interrupt NTZ.

Introduction For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. Aim This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020. Development This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed. Conclusions Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS.

The Post-ECTRIMS Meeting is an emblematic event in the field of multiple sclerosis in Spain. Its chief aim is bring together the country's leading specialist neurologists to analyse the main advances made in multiple sclerosis and to review the most important topics addressed at the ECTRIMS Congress. The tenth Post-ECTRIMS Meeting was held in November 2017. Over the years this event has firmly established itself as an important meeting point where experts from all over the country get together to foster communication, establish synergies and promote and enhance research ultimately aimed at improving the prognosis and quality of life of patients with multiple sclerosis. This first part reports on the publication of the new European and American clinical guidelines on the use of disease-modifying treatments and the new diagnostic criteria. It also discusses the strategies for following up patients treated with disease-modifying therapies, reviews cerebral atrophy and biomarkers of neurodegeneration and neuroinflammation, and analyses the role of neuroglia in pathogenesis and treatment. The study examines the natural history of the disease, with the evidence provided by registers, and we anticipate the future thanks to the progress being made in genetics and immunology.Revision de las novedades del Congreso ECTRIMS 2017, presentadas en la X Reunion Post-ECTRIMS (I).La reunion Post-ECTRIMS es una reunion emblematica en el ambito de la esclerosis multiple en España, con el claro objetivo de analizar, de la mano de reconocidos neurologos especialistas nacionales, los principales avances en esclerosis multiple y revisar los temas mas importantes del congreso ECTRIMS. En noviembre de 2017, la reunion Post-ECTRIMS celebro su decima edicion, y se ha consolidado como un importante foro de encuentro de expertos en nuestro pais para favorecer la comunicacion, establecer sinergias, y promover y potenciar la investigacion para mejorar, en ultima instancia, el pronostico y la calidad de vida de los pacientes con esclerosis multiple. En esta primera parte se avanza la publicacion de las nuevas guias clinicas europea y americana para el uso de los tratamientos modificadores de la enfermedad, y los nuevos criterios diagnosticos. Se discuten las estrategias para el seguimiento de los pacientes tratados con terapias modificadoras de la enfermedad, se revisan la atrofia cerebral y los biomarcadores de neurodegeneracion y neuroinflamacion, y se analiza el papel de la neuroglia en la patogenia y el tratamiento. Se hace un recorrido por la historia natural de la enfermedad, con la evidencia que aportan los registros, y nos adelantamos al futuro gracias a los avances en genetica e inmunologia.

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.

Introduction: We evaluated the effectiveness of natalizumab in patients with highly active, relapsing-remitting multiple sclerosis (HA-RRMS) to identify baseline predictors associated with freedom from disease activity. Methods: We analyzed 70 patients treated with natalizumab and followed for at least 1 year with progression of disability of ≥1 point on the EDSS before starting therapy. We recorded freedom from clinical activity, radiological activity, and disease activity (clinical and radiological). Results: The median (IQR) follow-up was 2.3 (2.0-3.8) years. Of the 52 patients who completed 2 years of treatment, 25 were free of disease activity (48.1%). The ARR decreased from a mean ± SD of 2.49 ± 0.86 at baseline to 0.47 ± 0.83 at the end of the first year (p < 0.001) and 0.34 ± 0.69 at the end of the second year (p < 0.001). The percentage of patients with gadolinium-enhanced lesions decreased from 21 at baseline to 5.7 at the end of the first year (p < 0.001) and to 5.8 during the second year (p < 0.005). Baseline EDSS ≤3.0 was significantly associated with freedom from disease activity (OR, 2.49; 95% CI, 1.24-4.99; p = 0.010). Conclusions: Natalizumab is effective in patients with HA-RRMS. Baseline EDSS ≤3.0 increases the probability of remaining disease-free in HA-RRMS treated with natalizumab.

INTRODUCTION: Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM: To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT: This first part addresses the latest studies on vitamin D deficiency and the discrepancies that currently exist regarding its treatment. The advances made in epigenetics allow us to present this approach as a possible biomarker of multiple sclerosis. An account is provided to explain the growing importance of imaging techniques to detect atrophy and other phenomena that occur during the disease, such as changes in iron concentration or remyelination processes, which allow us to further our understanding of the mechanisms of cortical pathology, and the dimensionality of neurodegeneration during its course. Findings related to immunological mechanisms and advances in potential antigen-specific therapies are discussed. The contribution presents the latest studies on the assessment of cognitive impairment and its rehabilitation, which are becoming increasingly important due to the high prevalence of these disorders and the absence of their systematic assessment in clinical practice. Finally, the unmet social and health needs of multiple sclerosis patients in our country are presented, with emphasis on the current deficits in the system of social protection.

INTRODUCTION Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT In this second part, the most recent evidence on the use of disease-modifying treatments during pregnancy is presented. Details are provided concerning the results of phase 3 clinical trials conducted to evaluate the efficacy and safety of two potential disease-modifying treatments for relapsing-remitting multiple sclerosis: ponesimod and ofatumumab. For the progressive forms, both available disease modifying treatments and others still in the research phase are reviewed. In the field of stem cell therapies, the article includes the results of the only clinical trial carried out to date comparing patients with relapsing-remitting multiple sclerosis treated with autologous haematopoietic stem cell transplantation and those treated with disease-modifying therapies. There are no important developments as regards symptomatic treatments, although the European Academy of Neurology has published a guide on palliative care. The various sources of information that collect pharmacovigilance data in the post-marketing setting are reviewed. CONCLUSIONS Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available.

Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice.Revision de las novedades del XXXI Congreso ECTRIMS 2015, presentadas en la VIII Reunion Post-ECTRIMS.Reconocidos especialistas nacionales en esclerosis multiple (EM) se han reunido, por octavo año consecutivo, para exponer lo mas novedoso que se presento en la ultima edicion del congreso ECTRIMS 2015 y que recoge esta revision. En esta edicion ha destacado la nueva clasificacion de los fenotipos de la EM. Tambien se revisaron los criterios diagnosticos del espectro de la neuromielitis optica y los problemas en el diagnostico diferencial derivados de la falta de definicion del espectro radiologico. La microbiota adquiere protagonismo como posible factor determinante de la enfermedad, junto con factores extrinsecos como el tabaco, la ingesta de sal o el deficit de vitamina D. Los avances en inmunomodulacion impulsan el progreso en el tratamiento de la EM. El ocrelizumab es el primer tratamiento con resultados positivos en las formas primariamente progresivas, y el tocilizumab, un farmaco para la artritis reumatoide, destaca como candidato potencial para el tratamiento de la neuromielitis optica. Ciertos antibioticos y vitaminas tambien podrian tener un papel en el tratamiento de la EM. En esta edicion se presto especial atencion a la terapia personalizada. Actualmente disponemos de 11 farmacos aprobados en Europa. Se necesitan algoritmos terapeuticos que nos ayuden a elegir el mejor tratamiento para cada paciente. Asimismo, necesitamos poder identificar en los estadios precoces de la enfermedad el riesgo de desarrollar discapacidad, para diseñar estrategias terapeuticas, para lo que se precisan biomarcadores moleculares y otras herramientas pronosticas. Los problemas aun existentes en la tecnologia del software en resonancia magnetica dificultan su traslacion a la practica clinica diaria.

Background and objective: The HLA-DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA-DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS. Methods: The HLA-DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA-DRB1 allelic frequencies were compared between OCB-positive and OCB-negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA-DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB. Results: We found 206 OCB-positive and 62 OCB-negative patients. The HLA-DRB1*15 allele in OCB-positive patients had a higher frequency when compared with OCB-negative patients (39.3% in OCB-positive vs. 16.1% in OCB-negative, OR = 1.38 95% CI = 1.18–1.61, P

La reunion Post-ECTRIMS se celebro por undecimo ano consecutivo el pasado octubre de 2018 en Madrid, con el objetivo de analizar los avances en esclerosis multiple destacados en el ultimo congreso anual ECTRIMS. Fruto de esta reunion, formada por los lideres de opinion en esclerosis multiple de ambito nacional, se presentan dos articulos de revision. En esta segunda parte, se incluye el creciente numero de evidencias que confirman la seguridad de la exposicion a los tratamientos modificadores de la enfermedad en mujeres que planifican un embarazo, y el efecto beneficioso de la lactancia, siempre y cuando la enfermedad no este muy activa. Se abordan los datos que muestran como la aplicacion de los criterios de McDonald de 2017 en poblacion pediatrica ha mejorado considerablemente el diagnostico en comparacion con los criterios anteriores. En cuanto a la esclerosis multiple progresiva, los resultados de los farmacos neuroprotectores son poco concluyentes, pero se proponen biomarcadores para mejorar la evaluacion de la respuesta terapeutica. Los estudios sobre tratamientos de reparacion de la mielina sugieren que la remielinizacion en la esclerosis multiple es posible. De igual manera, se exponen indicios favorables sobre el trasplante de celulas madre hematopoyeticas, siempre que se seleccione adecuadamente a los pacientes. Por otro lado, se revisan las similitudes y diferencias de las recomendaciones de las nuevas guias de practica clinica publicadas. Por ultimo, los resultados positivos de la rehabilitacion cognitiva y motora con el uso de las nuevas tecnologias vaticinan la incorporacion sistematica de estas herramientas en el tratamiento de la enfermedad en un futuro proximo.

Background and objective: The association of HLA-DRB1*15 with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical phenotype is still controversial. The objectives of this study are to investigate the influence of the HLA-DRB1 alleles on the genetic susceptibility to MS and to study their impact on disability progression in a Spanish population. Methods: HLA-DRB1 typing was performed by PCR-SSP in 380 patients with sporadic MS and 1088 unrelated healthy controls. Allelic frequencies were compared between groups. We studied the correlation between the different alleles and the progression of MS. Results: The HLA-DRB1*15 allele in patients with MS had a statistically significant higher frequency when compared with controls (18.9% in patients vs. 10.1% in controls, Odds ratio (OR) = 2.07, 95% CI = 1.64–2.60, P

Background and objective: Anticipation of age at onset in the younger generations is a widely known characteristic of many diseases with genetic inheritance. This study was performed to assess whether there is anticipation of age at onset in younger generations of familial multiple sclerosis (MS) in a Spanish population and to compare clinical characteristics of familial and sporadic MS. Methods: We studied a cohort of 1110 patients diagnosed with MS and followed-up in our MS Unit. Patients were considered as familial MS if they had in their family at least one relative of first or second degree diagnosed with MS. Otherwise, patients were considered to have sporadic MS. We compared the age at onset between relatives from different generations, and we also compared the age at onset of familial and sporadic MS. Results: A lower age at onset in the younger generations was found (median 22 years vs. 30 years, P

The aim of this study is to investigate whether induction of myxovirus resistance protein A (MxA) mRNA after 3 months of interferon-β administration is related to the treatment response in multiple sclerosis (MS) patients. In this prospective study, MS patients were enrolled before starting treatment. Demographic, clinical and radiological variables were recorded. Blood samples were obtained before, and at 3 and 12 months after interferon-β treatment. Real-time PCR was used to analyze MxA mRNA expression. Patients were classified as MxA-low or -high depending on MxA levels at baseline, and as MxA-induced or -non-induced according to whether an increase in MxA expression was detected at month 3. Time to the next relapse was investigated using Cox proportional hazards regression analysis. One hundred and four patients were selected and followed for a median of 2.2 years (IQR 1.6-3.5). On Cox regression analysis, a higher EDSS score before treatment (HR 1.57; 95 % CI 1.02-2.40; p = 0.039), MxA-high status at baseline (HR 2.71; 95 % CI 1.26-5.81; p = 0.010), and MxA-non-induced at month 3 (HR 2.49; 95 % CI 1.08-5.68; p = 0.031), were predictors of poor response to interferon-β in naive MS patients. Patients showing a lower capacity for MxA induction following 3 months of interferon-β treatment are more likely to be non-responders to this therapy.

Objective: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing–remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS. Methods: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years. Results: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05). Conclusions: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.

Background/aim - There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time. Methods - The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method. Results - Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found. Conclusion - Anticipation of age at onset is undetectable when adjusted for follow-up time.

Background: Patients with a first episode of longitudinal extensive transverse myelopathy (LETM) were reviewed with two objectives: to evaluate the clinical spectrum of LETM and to analyze the related clinical and laboratory variables that can be used as functional prognostic markers. Methods: A retrospective review was conducted of clinical, radiologic and biochemical data of patients admitted for LETM between 1993 and 2011. Results: Our cohort included 72 patients [median age 41 years, interquartile range (IQR) 29-61.5]. Median follow-up was 34 months (IQR 17.2-63). The modified Rankin Scale (mRS) score was ≥2 at the end of follow-up in 72.2%. The final diagnosis was idiopathic LETM in 22 patients, multiple sclerosis in 18, parainfectious disease in 11, systemic disease in 9, spinal cord infarction and neuromyelitis optica spectrum disorders in 3 patients each, and acute demyelinating encephalomyelitis, dural fistula, and tumor-related LETM in 2 patients each. Unfavorable outcome was associated with mRS ≥2 at admission [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.16-1.66] and older age (OR 1.06, 95% CI 1.01-1.11). Conclusion: Idiopathic LETM was the most frequent diagnosis at the end of follow-up. Older age and clinically severe disease at onset were independent prognostic factors of poorer functional recovery.

The HLA-DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA-DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS.The HLA-DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA-DRB1 allelic frequencies were compared between OCB-positive and OCB-negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA-DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB.We found 206 OCB-positive and 62 OCB-negative patients. The HLA-DRB1*15 allele in OCB-positive patients had a higher frequency when compared with OCB-negative patients (39.3% in OCB-positive vs. 16.1% in OCB-negative, OR = 1.38 95% CI = 1.18-1.61, P0.001). The other alleles did not show differences. When we compared with controls, the HLA-DRB1*15 allele was associated with the disease only in the OCB-positive patients group. None of the 55 genotypes found showed any association with the presence or absence of OCB.HLA-DRB1*15 allele is associated with OCB-positive patients with MS when studying a Spanish MS population.

There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time.The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method.Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found.Anticipation of age at onset is undetectable when adjusted for follow-up time.

Multiple sclerosis (MS) has been consistently associated with the HLA-DR2 haplotype and particularly with the HLA-DRB1*15 allele. Epistatic interactions between both parental alleles in the DRB1 loci have been shown to modify the MS susceptibility risk. This study investigated the frequencies of various HLA-DRB1 genotypes, their impact on MS susceptibility and their correlation with the clinical severity in a Spanish population.A genotype was considered as the combination of the two parental DRB1 alleles. We compared the frequencies of the genotypes in a sporadic MS population (n=380) with those of an unrelated healthy control cohort (n=1088). We correlated the different genotypes with the age at onset, gender distribution, symptoms at onset, course of the disease and progression severity by means of the time to reach the progressive phase and EDSS scores of 3 and 6.We found 81 different genotypes. There were four different MS-predisposing genotypes. Three of them contained the DRB1*15 allele (DRB1*03/15, DRB1*04/15, and DRB1*08/15) and the fourth was homozygote for the DRB1*03 allele. The highest odds ratio was found with the genotype DRB1*08/15 (OR=3.88, 95% CI=1.83-8.26, p0.01), followed by DRB1*03/03 (OR=3.15, 95% CI=1.93-5.14, p0.01), DRB1*03/15 (OR=2.72, 95% CI=1.88-3.94, p0.01) and DRB1*04/15 (OR=2.54, 95% CI=1.64-3.98, p0.01). The DRB1*01/04 and the DRB1*15/15 genotypes were associated with a shorter time to reach an EDSS score of 6.Our results show the importance of epistatic interactions among the HLA-DRB1 alleles, modifying the risk for MS as well as its clinical severity.

Anticipation of age at onset in the younger generations is a widely known characteristic of many diseases with genetic inheritance. This study was performed to assess whether there is anticipation of age at onset in younger generations of familial multiple sclerosis (MS) in a Spanish population and to compare clinical characteristics of familial and sporadic MS.We studied a cohort of 1110 patients diagnosed with MS and followed-up in our MS Unit. Patients were considered as familial MS if they had in their family at least one relative of first or second degree diagnosed with MS. Otherwise, patients were considered to have sporadic MS. We compared the age at onset between relatives from different generations, and we also compared the age at onset of familial and sporadic MS.A lower age at onset in the younger generations was found (median 22 years vs. 30 years, P0.001) and a significant lower age at onset of the disease in familial MS comparing to sporadic MS (median 25 years vs. 29 years, P = 0.042).There is an anticipation of the age at onset of MS in the younger generations of patients with familial MS. There is also a lower age at onset in familial versus sporadic MS.

Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice.

Introduccion. La paraparesia por afectacion vascular cerebral es infrecuente, aunque se observa en infartos de ambas arterias cerebrales anteriores (ACA), en sindromes de insuficiencia vertebrobasilar o en infartos de territorios frontera de la circulacion anterior. Caso clinico. Varon de 52 anos, diestro, con antecedentes de hipertension arterial, que consulto por dos episodios transitorios de paraparesia, de 5 minutos y 15 horas de duracion. Durante el ultimo episodio, se objetivo la presencia de una paraparesia y un Babinski izquierdo. Las exploraciones complementarias practicadas para el estudio de patologia medular fueron negativas. Una RM craneal mostro unicamente infartos lacunares bilaterales en territorios profundos. Cuatro meses despues, el paciente presento un episodio de afasia motora y parestesias de la extremidad inferior derecha, autolimitado en 10 minutos. La ecografia Doppler de los troncos supraorticos revelo una estenosis significativa de carotida interna izquierda (CII) y una oclusion de la derecha (CID). La arteriografia de los troncos supraorticos demostro una estenosis del 99% de la CID y del 95% de la CII, con vascularizacion de ambas ACA dependientes de la CII. Se practico una endarterectomia carotidea izquierda, y el paciente permanecio asintomatico hasta la actualidad. Conclusion. En nuestro paciente, ambas ACA dependian del flujo de la CII. Por ello, consideramos que el cuadro de paraparesia transitoria fue secundario a la estenosis carotidea izquierda, bien por un mecanismo hemodinamico o embolico arteria­arteria.

Por septimo ano consecutivo se ha celebrado en Madrid (Espana) la Reunion Post-ECTRIMS. Reconocidos especialistas en esclerosis multiple y lideres de opinion nacionales se han reunido un ano mas para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunion se genera esta revision que sale publicada en dos partes. Como principales conclusiones de esta primera parte se destaca el mayor entendimiento del componente genetico de la esclerosis multiple al que estamos asistiendo, el cual no resulta suficiente si no se considera su interaccion con los factores ambientales de riesgo de la enfermedad, ni el impacto de la comorbilidad y de las conductas saludables en la susceptibilidad y pronostico de los pacientes. Al respecto, los autores insisten en que, en la practica clinica, las alteraciones cognitivas y psiquiatricas estan infradiagnosticadas y son poco consideradas en la investigacion clinica; no obstante, la evidencia, aunque escasa, apunta hacia posibles beneficios de los farmacos modificadores de la enfermedad y alternativas al tratamiento inhibidor selectivo de la recaptacion de serotonina. El abordaje de las subpoblaciones en esclerosis multiple y variantes de la enfermedad refuerza la importancia del diagnostico precoz y preciso para ofrecer a los pacientes un pronostico y un tratamiento mas seguros y personalizados. La esclerosis multiple pediatrica es idonea para estudiar factores de riesgo de la enfermedad, pero dada su baja prevalencia, se cuestionan los estudios prospectivos y se aboga por los estudios colaborativos.

Background Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta. Methods Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups. Results 104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p

The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in an article in two parts. This second part covers the health of women and elderly MS patients, new trends in the treatment of cognitive impairment, focusing particularly on meditation, neuroeducation and cognitive rehabilitation, and introduces the concept of fatigability, which has been used to a limited extent in MS. The key role of digitalization and artificial intelligence in the theoretically near future is subject to debate, along with the potential these technologies can offer. The most recent research on the various treatment algorithms and their efficacy and safety in the management of the disease is reviewed. Finally, the most relevant data for cladribine and evobrutinib are presented, as well as future therapeutic strategies currently being investigated.