Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part I)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.

Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis.

INTRODUCTION: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between neurology and neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. METHODS: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. RESULTS: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. CONCLUSIONS: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.

13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (II). / XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II).

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.

TITLE: 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.

13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (I). / XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).

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.

TITLE: 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.

Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis. / Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple.

INTRODUCTION: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. METHODS: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. RESULTS: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. CONCLUSIONS: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.

Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement. / Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español.

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

12th Post-ECTRIMS Meeting: review of the novelties from the 2019 ECTRIMS Congress (II). / XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (II).

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.

TITLE: 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.

[12th Post-ECTRIMS Meeting: review of the novelties from the 2019 ECTRIMS Congress (I)]. / XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (I).

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.

TITLE: XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (I).Introducción. Como cada año, tras la celebración del Congreso 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. Esta primera parte aborda los últimos estudios sobre el déficit de vitamina D y las discrepancias existentes acerca de su tratamiento. Los avances en epigenética realizados permiten presentar esta aproximación como un posible biomarcador de la esclerosis múltiple. Se explica el creciente protagonismo de las técnicas de imagen para detectar la atrofia y otros fenómenos que acontecen durante la enfermedad, como los cambios en la concentración de hierro o los procesos de remielinización, que nos permiten ganar comprensión sobre los mecanismos de la patología cortical, y sobre la dimensionalidad de la neurodegeneración durante su evolución. Se discuten los hallazgos relacionados con los mecanismos inmunológicos y los avances realizados en las potenciales terapias específicas del antígeno. Se presentan los últimos estudios sobre la evaluación del deterioro cognitivo y su rehabilitación, que cobran cada vez más importancia por la alta prevalencia de estas alteraciones y por la ausencia de su evaluación sistemática en la práctica clínica. Por último, se exponen las necesidades sociosanitarias no cubiertas de los pacientes de esclerosis múltiple en nuestro país, poniendo el acento en los déficits actuales del sistema de protección social.

[EMCAM (Multiple Sclerosis Autonomous Community of Madrid) document for the management of patients with multiple sclerosis during the SARS-CoV-2 pandemic]. / Documento EMCAM (Esclerosis Múltiple Comunidad Autónoma de Madrid) para el manejo de pacientes con esclerosis múltiple durante la pandemia de SARS-CoV-2.

INTRODUCTION: The current SARS-CoV-2 pandemic is forcing neurologists to carry out a series of adaptations in the management of multiple sclerosis. Neurologists must weigh up the need to start or continue disease-modifying treatments against the risk of infection, the risk of complications from the infection, and the risk of multiple sclerosis activity. Since this is an unprecedented situation, most decisions are being made on the basis of a theoretical approach and the criteria of each neurologist. AIMS: The aim of this study is conduct a literature search to collect available evidence on the relationship between disease-modifying therapies in multiple sclerosis and SARS-CoV-2 infection. This evidence, together with the experience of the authors in the management of patients with multiple sclerosis during the pandemic, will make it possible to offer some proposals for the treatment and follow-up of patients in this epidemiological context. DEVELOPMENT: After the literature search and our experience in the management of patients, a number of proposals for treatment are established for each drug, which must necessarily be individualised for each patient, since, in these exceptional circumstances, their peculiarities can affect the prognosis. CONCLUSIONS: The neurologist should be aware of current evidence to assess the risk-benefit of starting, maintaining and stopping disease-modifying therapies in multiple sclerosis during the pandemic.

TITLE: Documento EMCAM (Esclerosis Múltiple Comunidad Autónoma de Madrid) para el manejo de pacientes con esclerosis múltiple durante la pandemia de SARS-CoV-2.Introducción. La pandemia actual por el SARS-CoV-2 está obligando a los neurólogos a una serie de adaptaciones en el manejo de la esclerosis múltiple. Los neurólogos deben sopesar la necesidad de iniciar o continuar los tratamientos modificadores de la enfermedad en función del riesgo de infección, del riesgo de complicaciones de la infección y del riesgo de actividad de la esclerosis múltiple. Dado que ésta es una situación sin precedentes, la mayoría de las decisiones se están tomando sobre la base de un abordaje teórico y del criterio de cada neurólogo. Objetivos. Se pretende, a través de una búsqueda bibliográfica, recopilar la evidencia disponible sobre la relación entre tratamientos modificadores de la enfermedad en la esclerosis múltiple y la infección por el SARS-CoV-2. Esta evidencia, junto con la experiencia de los autores en el manejo de pacientes con esclerosis múltiple durante la pandemia, permitirá brindar algunas propuestas de tratamiento y seguimiento de los pacientes en este contexto epidemiológico. Desarrollo. Después de la búsqueda bibliográfica y de nuestra experiencia en el manejo de pacientes, se establecen unas propuestas de tratamiento sobre cada fármaco que necesariamente han de individualizarse para cada paciente, ya que, en esta circunstancia excepcional, sus peculiaridades pueden marcar el pronóstico. Conclusiones. El neurólogo debe tener conocimiento de la evidencia actual para valorar el riesgo-beneficio de iniciar, mantener y suspender los tratamientos modificadores de la enfermedad en la esclerosis múltiple durante la pandemia.

[Review of the novelties presented at the 2018 ECTRIMS Congress: 11th Post-ECTRIMS Meeting (I)]. / Revision de las novedades presentadas en el congreso ECTRIMS 2018: XI Reunion Post-ECTRIMS (I).

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.

TITLE: 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.

Review of the novelties presented at the 2018 ECTRIMS Congress: 11th Post-ECTRIMS Meeting (II). / Revision de las novedades presentadas en el Congreso ECTRIMS 2018: XI Reunion Post-ECTRIMS (II).

The Post-ECTRIMS Meeting was held for the eleventh consecutive year in October 2018 in Madrid, with the aim of analysing the advances made in multiple sclerosis that were highlighted at the latest ECTRIMS annual congress. Based on the issues discussed at this meeting, attended by the nation's foremost opinion leaders on multiple sclerosis, two review articles are presented. This second part includes the growing body of evidence confirming the safety of exposure to disease-modifying treatments in women planning a pregnancy, and the beneficial effect of breastfeeding, provided that the disease is not very active. It addresses data showing how the application of the 2017 McDonald criteria in the paediatric population has significantly improved diagnosis compared to the previous criteria. With regard to progressive multiple sclerosis, the results of neuroprotective drugs are inconclusive, but biomarkers are proposed to improve the evaluation of the therapeutic response. Studies on myelin repair treatments suggest that remyelination in multiple sclerosis is possible. Likewise, there are favourable indications for haematopoietic stem cell transplantation, provided that patients are selected appropriately. On the other hand, we also conduct a review of the similarities and differences of the recommendations in the new clinical practice guidelines. Finally, the positive results of cognitive and motor rehabilitation with the use of new technologies point to the systematic incorporation of these tools in the treatment of the disease in the near future.

TITLE: Revision de las novedades presentadas en el Congreso ECTRIMS 2018: XI Reunion Post-ECTRIMS (II).La reunion Post-ECTRIMS se celebro por undecimo año 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.

Clinical usefulness of prognostic biomarkers in optic neuritis.

BACKGROUND AND PURPOSE: Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis. METHODS: Sixty-eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid-specific oligoclonal IgM bands (LS-OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored. RESULTS: The mean time of follow-up of our series was 46.4 months. Twenty-five patients (36.7%) developed CDMS during follow-up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5, P = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3, P = 0.003) and LS-OCMBs were associated with a shorter time to CDMS (HR = 116.6, P < 0.001). CONCLUSIONS: Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS-OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions.

Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis.

Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56(bright) /CD56(dim) ) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56(bright) and NK T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease.

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis.

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) neurofilament light protein (NFL) is a promising biomarker of axonal injury and neurodegeneration. Here CSF lymphocyte subpopulations and antibodies, potential players of neurodegeneration, are examined in relation to CSF NFL shedding in MS. METHODS: Cerebrospinal fluid NFL from 127 consecutive untreated MS patients was analysed. Samples from 37 age-matched patients with other central nervous system non-inflammatory neurological diseases (NIND) were also assessed. CD4+, CD8+, CD56+ and CD19+ cell subsets were studied by flow cytometry. Oligoclonal IgG and IgM bands (OCMB) against lipids were studied by isoelectric focusing and immunoblotting. These data were analysed in relation to clinical and magnetic resonance imaging features. RESULTS: A CSF NFL cut-off value of 900 ng/l (mean + 3 SD of NIND values) was calculated. MS patients with increased NFL values showed significantly higher Multiple Sclerosis Severity Score and magnetic resonance imaging lesion number. The presence of OCMB (P < 0.0001) and elevated T and B lymphocyte counts was associated with increased levels of CSF NFL. CONCLUSIONS: High CSF NFL levels are associated with elevated CSF lymphocyte cell counts and intrathecal synthesis of IgM against lipids. These findings support a role for OCMB in the axonal damage of MS offering a rationale for the association of these antibodies with disability and brain atrophy progression in MS.

Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis.

BACKGROUND AND PURPOSE: Different data show an association between human herpesvirus 6 (HHV-6) and multiple sclerosis (MS). Intrathecal anti-HHV-6 immunoglobulin G (IgG) was detected in MS patients, but the antigen recognized by cerebrospinal fluid (CSF) IgG has not been characterized yet. Our objective was to identify the HHV-6 antigens recognized by IgG present in the CSF of patients with MS. METHODS: Cerebrospinal fluid IgG of 15 MS patients and eight patients with other neurological diseases was purified on protein G Sepharose columns. Purified IgG from every patient was linked to a CNBr-activated Sepharose 4B column. Fifty micrograms of viral extract was applied to each column. Bound proteins were eluted and analysed by SDS-PAGE and silver staining. The viral protein was characterized by mass spectrometry. RESULTS: A protein of 150 kD was eluted from CSF IgG columns of three of eight patients with primary progressive MS and one of seven with relapsing-remitting MS. After digestion and mass spectrometry analysis 10 peptides were found with 100% homology with the major capsid protein of the HHV-6A. DISCUSSION: These findings confirm the presence of anti-HHV-6 IgG in CSF of MS patients, particularly in progressive forms, and identify major capsid protein as the major antigen recognized by CSF IgG from MS patients.

[Recommendations for the clinical use of motor evoked potentials in multiple sclerosis]. / Recomendaciones para la utilización clínica del estudio de potenciales evocados motores en la esclerosis múltiple.

OBJECTIVE: To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. METHOD: We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. RESULTS: MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. CONCLUSIONS: Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space.

Spasticity improvement in patients with relapsing-remitting multiple sclerosis switching from interferon-ß to glatiramer acetate: the Escala Study.

BACKGROUND: A recent pilot study suggested spasticity improvement during glatiramer acetate (GA) treatment in multiple sclerosis (MS) patients who previously received interferon-ß (IFN-ß). OBJECTIVE: To evaluate changes in spasticity in MS patients switching from IFN-ß to GA. METHODS: Observational, multicentre study in patients with relapsing-remitting MS (RRMS) and spasticity switching from IFN-ß to GA. The primary endpoint comprised changes on Penn Spasm Frequency Scale (PSFS), Modified Ashworth Scale (MAS), Adductor Tone Rating Scale (ATRS), and Global Pain Score (GPS) at months 3 and 6 after starting GA. RESULTS: Sixty-eight evaluable patients were included (mean age,41.7±9.5 years; female,70.6%; mean time from MS diagnosis to starting GA,7.6±5.7 years). Previous treatments were subcutaneous IFN-ß1a in 42.6% patients, intramuscular IFN-ß1a in 41.2% and IFN-ß1b in 32.4%, whose mean durations were 3.5±3.3, 2.7±2.5 and 4.4±3.6 years, respectively. Statistically significant reductions in mean scores on all spasticity measurements were observed from baseline to month 3 (PSFS, 1.7±0.9 vs 1.4±0.6, p<0.01; MAS, 0.7±0.5 vs 0.6±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.7±0.8, p<0.01; ATRS, 1.6±0.6 vs 1.4±0.6, p<0.01; GPS, 29.4±22.1 vs 24.7±19.4, p<0.01) and from baseline to month 6 (PSFS, 1.7±0.9 vs 1.3±0.6, p<0.01; MAS, 0.7±0.5 vs 0.5±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.5±0.9, p<0.01; ATRS, 1.6±0.6 vs 1.3±0.6, p<0.01; GPS, 29.4±22.1 vs 19.1±14.8, p<0.01). CONCLUSION: Spasticity improvement in terms of spasm frequency, muscle tone and pain can be noted after three months and prolonged for six months of GA treatment.