Documento de consenso de la Sociedad Española de Neurología sobre el tratamiento de la esclerosis múltiple y manejo holístico del paciente 2023 / Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023

El último documento de consenso del Grupo de Estudio de Enfermedades Desmielinizantes de la Sociedad Española de Neurología sobre el tratamiento de la esclerosis múltiple (EM) data del año 2016. Aunque muchas consideraciones continúan todavía vigentes, desde entonces se han producido cambios significativos en el manejo y tratamiento de esta enfermedad, motivados no solo por la aprobación de nuevos fármacos con diferentes mecanismos de acción, sino también por la evolución de conceptos otrora consolidados. Esto ha permitido abordar situaciones especiales como el embarazo y la vacunación desde otra perspectiva, e incluir nuevas variables en la toma de decisiones en práctica clínica, como plantear tratamiento modificador de la enfermedad (TME) de alta eficacia en fases tempranas, considerar la perspectiva del paciente y utilizar nuevas tecnologías como monitorización remota. Estos cambios han motivado la presente actualización del consenso mediante metodología Delphi, con el objetivo de reflejar el nuevo paradigma de manejo del paciente con EM basándose en la evidencia científica y la experiencia clínica de los participantes. Entre las principales conclusiones destacan como recomendaciones: iniciar TME inmunomodulador en el síndrome radiológico aislado con actividad radiológica persistente, evaluar la perspectiva del paciente y abandonar la terminología «líneas de tratamiento» en la clasificación de los TME (consenso mayor del 90%). Tras el diagnóstico de EM la elección del primer TME debería considerar la presencia/ausencia de factores de mal pronóstico (epidemiológicos, clínicos, radiológicos y biomarcadores) para la aparición de nuevos brotes o progresión de discapacidad, pudiendo plantear desde el inicio TME de alta eficacia. (AU)

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. (AU)

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.

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

Introducción: El uso de la resonancia magnética (RM) está ampliamente extendido en el diagnóstico y el seguimiento de los pacientes con esclerosis múltiple (EM). La coordinación entre los servicios de Neurología y Neurorradiología es clave para la realización e interpretación de estudios radiológicos de la manera más eficaz posible. Sin embargo, esta coordinación es susceptible de mejoras en una gran parte de los hospitales nacionales. Métodos: Un panel de 17 neurólogos y neurorradiólogos de 8 hospitales españoles, presencialmente y a través de comunicación online, consensuaron una guía de buenas prácticas en la coordinación en EM. La guía se estableció en 4 fases: 1) definición del alcance de la guía y metodología del estudio; 2) revisión bibliográfica sobre buenas prácticas o recomendaciones en el uso de la RM en EM; 3) discusión y búsqueda de consenso entre los expertos; y 4) formalización y validación de los contenidos para elaborar el documento de consenso. Resultados: Se consensuaron un total de 9 recomendaciones dirigidas a la mejora de la coordinación entre los servicios de Neurología y Neurorradiología, que se pueden resumir en: 1) estandarizar las solicitudes de RM, informes y planificación; 2) crear protocolos compartidos para los estudios de RM; 3) establecer comités multidisciplinares y sesiones de coordinación, y 4) generar canales de comunicación formales entre los profesionales de ambos departamentos. Conclusiones: Se espera que las recomendaciones consensuadas sirvan de guía para optimizar la coordinación entre neurólogos y neurorradiólogos y que repercutan en la mejora del diagnóstico y seguimiento de los pacientes con EM.(AU)

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.(AU)

[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.

Early beginning of alemtuzumab: Changing the multiple sclerosis treatment paradigm. Interim analysis of the LEMVIDA study.

INTRODUCTION: LEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain. METHODS: This is an interim analysis evaluating the baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria. RESULTS: 161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed). CONCLUSIONS: Unlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.

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.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España / Consensus statement on the use of alemtuzumab in daily clinical practice in Spain

Introducción: Alemtuzumab es un fármaco de alta eficacia aprobado por la Agencia Europea de Medicamentos como tratamiento modificador de la enfermedad en pacientes con esclerosis múltiple remitente recurrente.ObjetivoElaborar un documento de consenso sobre el manejo de alemtuzumab en la práctica clínica habitual, que sea de aplicación en el ámbito español.DesarrolloUn grupo de expertos en esclerosis múltiple revisó las publicaciones disponibles hasta diciembre de 2017, de tratamiento con alemtuzumab y esclerosis múltiple. Se incluyeron trabajos sobre eficacia, efectividad y seguridad, despistaje de infecciones y vacunación, administración y monitorización. La propuesta inicial de recomendaciones fue desarrollada por un grupo coordinador con base en la evidencia disponible y en su experiencia clínica. El proceso de consenso se llevó a cabo en 2 etapas; se estableció como porcentaje inicial de acuerdo grupal el 80%. El documento final con todas las recomendaciones acordadas por el grupo de trabajo se sometió a revisión externa y los comentarios recibidos fueron considerados por el grupo coordinador.ConclusionesEl documento aportado pretende ser una herramienta útil para facilitar el manejo del fármaco en condiciones de práctica clínica habitual. (AU)

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.ObjectiveA consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.DevelopmentA group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group.ConclusionThe present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice. (AU)

Experience with tocilizumab in patients with neuromyelitis optica spectrum disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system involving astrocytes, B lymphocytes, anti-aquaporin 4, and such inflammatory mediators as interleukin-6. Several immunosuppressants are used in their treatment. Tocilizumab, an interleukin-6 receptor antagonist, may be a treatment option. METHOD: We performed an observational, retrospective study analysing parameters of effectiveness (annualised relapse rate, disability, and radiological progression) and safety of tocilizumab in patients with NMOSD in whom previous immunosuppressant treatment had failed. We aimed to evaluate the effectiveness and safety of tocilizumab in clinical practice in patients with NMOSD not responding to other immunosuppressants. RESULTS: Five patients with NMOSD were analysed. Sixty percent of patients were women; mean age at diagnosis was 50±5.3 years and mean progression time was 4.5±3.6 years. Previously administered immunosuppressants were rituximab (in all 5), cyclophosphamide (2), and azathioprine (1). Mean time of exposure to tocilizumab was 2.3±1 years. Mean annualised relapse rate was 1.8±1.3 in the year prior to the introduction of tocilizumab and 0.2±0.4 the year after (P<.05), representing a reduction of 88.9%. CONCLUSIONS: In our experience, tocilizumab is safe and effective in patients with NMOSD showing no response to other immunosuppressants.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain. / Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry.

OBJECTIVE: To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. METHODS: An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. RESULTS: Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. CONCLUSIONS: The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.

Determinación plasmática de neurofilamentos como biomarcador en la esclerosis múltiple: conclusiones del foro EMotion / Plasma determination of neurofilaments as biomarkers in multiple sclerosis: conclusions of the EMotion Forum

Introducción: La identificación de biomarcadores de progresión de la enfermedad y de actividad clínica y subclínica continúa siendo una necesidad en el abordaje de la esclerosis múltiple (EM). Entre ellos, la determinación plasmática de niveles de los neurofilamentos de cadena ligera (NfL-PM) ha mostrado una posible correlación con la evolución clínica y la evaluación de la respuesta terapéutica en los pacientes con EM. Sin embargo, la determinación de NfL-PM afronta diversos obstáculos que dificultan su integración en la práctica asistencial, como la ausencia de valores normalizados y protocolos estandarizados. Objetivo: Este trabajo tiene un doble objetivo: a) revisar la evidencia sobre la utilidad en la práctica clínica de los NfL como biomarcadores de neurodegeneración e inflamación en la EM y b) recoger las conclusiones de un foro de expertos en EM reunidos para debatir sobre la utilidad y aplicabilidad de la determinación de NfL-PM en España (Foro EMotion 2020). Desarrollo: Los NfL-PM parecen particularmente útiles a la hora de determinar la actividad subclínica en la EM y ofrecen la posibilidad de identificar poblaciones con riesgo de desarrollo de EM, como los casos de síndrome radiológico aislado. Se deben considerar aspectos como la monitorización de fármacos modificadores de la enfermedad de inducción o la valoración de respuestas subóptimas para retirar fármacos modificadores de la enfermedad poco eficaces. Conclusiones: Los especialistas coincidieron en el potencial diagnóstico y pronóstico de la determinación de NfL-PM y en que su utilidad en la EM puede contribuir al desarrollo general de la técnica.(AU)

Introduction: In the management of multiple sclerosis (MS) there is still a need to identify biomarkers of disease progression, and clinical and subclinical activity. Among them, determination of neurofilament light chain plasma levels (NfL-PM) has shown a possible correlation with clinical course and assessment of therapeutic response in MS patients. However, the determination of NfL-PM has to overcome several obstacles that hinder its integration into healthcare practice, such as the absence of normalised values and standardised protocols. Aim: This article has two main aims: a) to review the evidence on the usefulness of NfL in clinical practice as biomarkers of neurodegeneration and inflammation in MS, and b) to pool the conclusions from a forum of MS experts gathered to discuss the usefulness and applicability of NfL-PM determination in Spain (EMotion Forum 2020). Development: NfL-PM seems particularly useful in determining subclinical activity in MS and offers the possibility of identifying populations at risk of developing MS, such as cases of radiologically isolated syndrome. Issues such as the monitoring of induction disease-modifying drugs or the assessment of suboptimal responses for the withdrawal of ineffective disease-modifying drugs should be considered. Conclusions: The experts agreed on the diagnostic and prognostic potential of NfL-PM determination and that its usefulness in MS can contribute to the general development of the technique.(AU)

[Plasma determination of neurofilaments as biomarkers in multiple sclerosis: conclusions of the EMotion Forum]. / Determinación plasmática de neurofilamentos como biomarcador en la esclerosis múltiple: conclusiones del foro EMotion.

INTRODUCTION: In the management of multiple sclerosis (MS) there is still a need to identify biomarkers of disease progression, and clinical and subclinical activity. Among them, determination of neurofilament light chain plasma levels (NfL-PM) has shown a possible correlation with clinical course and assessment of therapeutic response in MS patients. However, the determination of NfL-PM has to overcome several obstacles that hinder its integration into healthcare practice, such as the absence of normalised values and standardised protocols. AIM: This article has two main aims: a) to review the evidence on the usefulness of NfL in clinical practice as biomarkers of neurodegeneration and inflammation in MS, and b) to pool the conclusions from a forum of MS experts gathered to discuss the usefulness and applicability of NfL-PM determination in Spain (EMotion Forum 2020). DEVELOPMENT: NfL-PM seems particularly useful in determining subclinical activity in MS and offers the possibility of identifying populations at risk of developing MS, such as cases of radiologically isolated syndrome. Issues such as the monitoring of induction disease-modifying drugs or the assessment of suboptimal responses for the withdrawal of ineffective disease-modifying drugs should be considered. CONCLUSIONS: The experts agreed on the diagnostic and prognostic potential of NfL-PM determination and that its usefulness in MS can contribute to the general development of the technique.

TITLE: Determinación plasmática de neurofilamentos como biomarcador en la esclerosis múltiple: conclusiones del foro EMotion.Introducción. La identificación de biomarcadores de progresión de la enfermedad y de actividad clínica y subclínica continúa siendo una necesidad en el abordaje de la esclerosis múltiple (EM). Entre ellos, la determinación plasmática de niveles de los neurofilamentos de cadena ligera (NfL-PM) ha mostrado una posible correlación con la evolución clínica y la evaluación de la respuesta terapéutica en los pacientes con EM. Sin embargo, la determinación de NfL-PM afronta diversos obstáculos que dificultan su integración en la práctica asistencial, como la ausencia de valores normalizados y protocolos estandarizados. Objetivo. Este trabajo tiene un doble objetivo: a) revisar la evidencia sobre la utilidad en la práctica clínica de los NfL como biomarcadores de neurodegeneración e inflamación en la EM y b) recoger las conclusiones de un foro de expertos en EM reunidos para debatir sobre la utilidad y aplicabilidad de la determinación de NfL-PM en España (Foro EMotion 2020). Desarrollo. Los NfL-PM parecen particularmente útiles a la hora de determinar la actividad subclínica en la EM y ofrecen la posibilidad de identificar poblaciones con riesgo de desarrollo de EM, como los casos de síndrome radiológico aislado. Se deben considerar aspectos como la monitorización de fármacos modificadores de la enfermedad de inducción o la valoración de respuestas subóptimas para retirar fármacos modificadores de la enfermedad poco eficaces. Conclusiones. Los especialistas coincidieron en el potencial diagnóstico y pronóstico de la determinación de NfL-PM y en que su utilidad en la EM puede contribuir al desarrollo general de la técnica.

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.

Pulse immunosuppressive therapy for multiple sclerosis during the SARS-CoV-2 lockdown de-escalation plan: Safety algorithm. / Tratamiento inmunosupresor en pulsos en esclerosis múltiple durante el desescalado de la epidemia por SARS-CoV-2. Algoritmo de seguridad.

INTRODUCTION: The COVID-19 pandemic is changing approaches to diagnosis, treatment, and care provision in multiple sclerosis (MS). During both the initial and peak phases of the epidemic, the administration of disease-modifying drugs, typically immunosuppressants administered in pulses, was suspended due to the uncertainty about their impact on SARS-CoV-2 infection, mainly in contagious asymptomatic/presymptomatic patients. The purpose of this study is to present a safety algorithm enabling patients to resume pulse immunosuppressive therapy (PIT) during the easing of lockdown measures. METHODS: We developed a safety algorithm based on our clinical experience with MS and the available published evidence; the algorithm assists in the detection of contagious asymptomatic/presymptomatic cases and of patients with mild symptoms of SARS-CoV-2 infection with a view to withdrawing PIT in these patients and preventing new infections at day hospitals. RESULTS: We developed a clinical/microbiological screening algorithm consisting of a symptom checklist, applied during a teleconsultation 48hours before the scheduled session of PIT, and PCR testing for SARS-CoV-2 in nasopharyngeal exudate 24hours before the procedure. CONCLUSION: The application of our safety algorithm presents a favourable risk-benefit ratio despite the fact that the actual proportion of asymptomatic and presymptomatic individuals is unknown. Systematic PCR testing, which provides the highest sensitivity for detecting presymptomatic cases, combined with early detection of symptoms of SARS-CoV-2 infection may reduce infections and improve detection of high-risk patients before they receive PIT.

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.