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

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.(AU)

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

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.(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.

Validation of a New Semiautomated Segmentation Pipeline Based on the Spinal Cord Toolbox DeepSeg Algorithm to Estimate the Cervical Canal Area.

BACKGROUND AND PURPOSE: As in the brain reserve concept, a larger cervical canal area may also protect against disability. In this context, a semiautomated pipeline has been developed to obtain quantitative estimations of the cervical canal area. The aim of the study was to validate the pipeline, to evaluate the consistency of the cervical canal area measurements during a 1-year period, and to compare cervical canal area estimations obtained from brain and cervical MRI acquisitions. MATERIALS AND METHODS: Eight healthy controls and 18 patients with MS underwent baseline and follow-up 3T brain and cervical spine sagittal 3D MPRAGE. The cervical canal area was measured in all acquisitions, and estimations obtained with the proposed pipeline were compared with manual segmentations performed by 1 evaluator using the Dice similarity coefficient. The cervical canal area estimations obtained on baseline and follow-up T1WI were compared; brain and cervical cord acquisitions were also compared using the individual and average intraclass correlation coefficients. RESULTS: The agreement between the manual cervical canal area masks and the masks provided by the proposed pipeline was excellent, with a mean Dice similarity coefficient mean of 0.90 (range, 0.73-0.97). The cervical canal area estimations obtained from baseline and follow-up scans showed a good level of concordance (intraclass correlation coefficient = 0.76; 95% CI, 0.44-0.88); estimations obtained from brain and cervical MRIs also had good agreement (intraclass correlation coefficient = 0.77; 95% CI, 0.45-0.90). CONCLUSIONS: The proposed pipeline is a reliable tool to estimate the cervical canal area. The cervical canal area is a stable measure across time; moreover, when cervical sequences are not available, the cervical canal area could be estimated using brain T1WI.

Fármacos modificadores de la enfermedad en la esclerosis múltiple durante la lactancia: revisión de la evidencia actual / Disease-modifying drugs in multiple sclerosis during breastfeeding: a review of current evidence

Introducción: La esclerosis múltiple afecta principalmente a mujeres en edad fértil, y el período de gestación y posparto es de especial interés por las peculiaridades que comporta en cuanto a evolución de la enfermedad y por las consecuencias terapéuticas que se derivan. En el período de lactancia materna (LM), la elección de la estrategia de tratamiento debe poner en una balanza, por un lado, los beneficios bien establecidos de la LM para el recién nacido y su madre y, por el otro, el perfil de seguridad y potenciales efectos adversos en el lactante derivados de la exposición a los fármacos modificadores de la enfermedad, por transferencia a través de leche materna. Desarrollo: Se realiza una revisión de la evidencia actual acerca de la seguridad de los fármacos modificadores de la enfermedad disponibles para el tratamiento de la esclerosis múltiple durante el período de LM, y se recogen datos de transferencia de los diferentes fármacos a la leche materna, así como los potenciales efectos adversos descritos en el lactante. Los fármacos considerados de primera elección durante este período son el interferón beta y el acetato de glatiramer. El resto de los fármacos modificadores de la enfermedad no están aceptados para su utilización en el período de LM por ficha técnica. Sin embargo, en los últimos años, se han publicado datos de estudios de práctica clínica y series de casos que indican que algunos de estos fármacos podrían utilizarse con seguridad durante este período. Conclusiones: Teniendo en cuenta los beneficios reconocidos de la LM para la salud tanto de la madre como del lactante, se debe recomendar la LM exclusiva a las pacientes con esclerosis múltiple siempre que sea posible. Es fundamental realizar una evaluación individualizada previa al embarazo y valorar las diferentes opciones de tratamiento en función de cada paciente.(AU)

Introduction: Multiple sclerosis mainly affects women of childbearing age, and the pregnancy and postpartum period is of special interest because of the peculiarities of the disease course and the therapeutic consequences that derive from it. During the period of breastfeeding (BF), the choice of treatment strategy must weigh up the well-established benefits of BF for both the newborn and the mother against the safety profile and potential adverse effects on the infant resulting from exposure to disease-modifying drugs transferred through breast milk. Development: The study reviews the current evidence on the safety of disease-modifying drugs available for the treatment of multiple sclerosis during the BF period, and gathers data on the transfer of the different drugs into breast milk, as well as the potential adverse effects described in the infant. The drugs of first choice during this period are interferon beta and glatiramer acetate. The rest of the disease modifying drugs are not accepted for use in the BF period according to their summary of product characteristics. However, in recent years, data from studies of clinical practice and case series have been published suggesting that some of these drugs could be used safely during this period. Conclusions: Given the recognised health benefits of BF for both mother and infant, exclusive breastfeeding is recommended whenever possible. It is essential to carry out an individualised assessment prior to pregnancy and to evaluate the different treatment options depending on each patient.(AU)

[Esclerosis multiple. Lactancia. Lactante. Planificacion familiar. Posparto. Tratamiento modificador de la enfermedad.] / Fármacos modificadores de la enfermedad en la esclerosis múltiple durante la lactancia: revisión de la evidencia actual.

INTRODUCTION: Multiple sclerosis mainly affects women of childbearing age, and the pregnancy and postpartum period is of special interest because of the peculiarities of the disease course and the therapeutic consequences that derive from it. During the period of breastfeeding (BF), the choice of treatment strategy must weigh up the well-established benefits of BF for both the newborn and the mother against the safety profile and potential adverse effects on the infant resulting from exposure to disease-modifying drugs transferred through breast milk. DEVELOPMENT: The study reviews the current evidence on the safety of disease-modifying drugs available for the treatment of multiple sclerosis during the BF period, and gathers data on the transfer of the different drugs into breast milk, as well as the potential adverse effects described in the infant. The drugs of first choice during this period are interferon beta and glatiramer acetate. The rest of the disease modifying drugs are not accepted for use in the BF period according to their summary of product characteristics. However, in recent years, data from studies of clinical practice and case series have been published suggesting that some of these drugs could be used safely during this period. CONCLUSIONS: Given the recognised health benefits of BF for both mother and infant, exclusive breastfeeding is recommended whenever possible. It is essential to carry out an individualised assessment prior to pregnancy and to evaluate the different treatment options depending on each patient.

TITLE: Fármacos modificadores de la enfermedad en la esclerosis múltiple durante la lactancia: revisión de la evidencia actual.Introducción. La esclerosis múltiple afecta principalmente a mujeres en edad fértil, y el período de gestación y posparto es de especial interés por las peculiaridades que comporta en cuanto a evolución de la enfermedad y por las consecuencias terapéuticas que se derivan. En el período de lactancia materna (LM), la elección de la estrategia de tratamiento debe poner en una balanza, por un lado, los beneficios bien establecidos de la LM para el recién nacido y su madre y, por el otro, el perfil de seguridad y potenciales efectos adversos en el lactante derivados de la exposición a los fármacos modificadores de la enfermedad, por transferencia a través de leche materna. Desarrollo. Se realiza una revisión de la evidencia actual acerca de la seguridad de los fármacos modificadores de la enfermedad disponibles para el tratamiento de la esclerosis múltiple durante el período de LM, y se recogen datos de transferencia de los diferentes fármacos a la leche materna, así como los potenciales efectos adversos descritos en el lactante. Los fármacos considerados de primera elección durante este período son el interferón beta y el acetato de glatiramer. El resto de los fármacos modificadores de la enfermedad no están aceptados para su utilización en el período de LM por ficha técnica. Sin embargo, en los últimos años, se han publicado datos de estudios de práctica clínica y series de casos que indican que algunos de estos fármacos podrían utilizarse con seguridad durante este período. Conclusiones. Teniendo en cuenta los beneficios reconocidos de la LM para la salud tanto de la madre como del lactante, se debe recomendar la LM exclusiva a las pacientes con esclerosis múltiple siempre que sea posible. Es fundamental realizar una evaluación individualizada previa al embarazo y valorar las diferentes opciones de tratamiento en función de cada paciente.

SWI as an Alternative to Contrast-Enhanced Imaging to Detect Acute MS Lesions.

BACKGROUND AND PURPOSE: Acute inflammatory activity of MS lesions is traditionally assessed through contrast-enhanced T1-weighted MR images. The aim of our study was to determine whether a qualitative evaluation of non-contrast-enhanced SWI of new T2-hyperintense lesions might help distinguish acute and chronic lesions and whether it could be considered a possible alternative to gadolinium-based contrast agents for this purpose. MATERIALS AND METHODS: Serial MR imaging studies from 55 patients with MS were reviewed to identify 169 new T2-hyperintense lesions. Two blinded neuroradiologists determined their signal pattern on SWI, considering 5 categories (hypointense rings, marked hypointensity, mild hypointensity, iso-/hyperintensity, indeterminate). Two different blinded neuroradiologists evaluated the presence or absence of enhancement in postcontrast T1-weighted images of the lesions. The Fisher exact test was used to determine whether each category of signal intensity on SWI was associated with gadolinium enhancement. RESULTS: The presence of hypointense rings or marked hypointensity showed a strong association with the absence of gadolinium enhancement (P < .001), with a sensitivity of 93.0% and a specificity of 82.9%. The presence of mild hypointensity or isohyperintensity showed a strong association with the presence of gadolinium enhancement (P < .001), with a sensitivity of 68.3% and a specificity of 99.2%. CONCLUSIONS: A qualitative analysis of the signal pattern on SWI of new T2-hyperintense MS lesions allows determining the likelihood that the lesions will enhance after administration of a gadolinium contrast agent, with high specificity albeit with a moderate sensitivity. While it cannot substitute for the use of contrast agent, it can be useful in some clinical settings in which the contrast agent cannot be administered.

Factors associated with treatment escalation among MS specialists and general neurologists: Results from an International cojoint study.

BACKGROUND: Previous studies in multiple sclerosis (MS) showed that therapeutic inertia (TI) affects 60-90% of neurologists and up to 25% of daily treatment decisions. The objective of this study was to determine the most common factors and attribute levels associated with decisions to treatment escalation in an international study in MS care. METHODS: 300 neurologists with MS expertise from 20 countries were invited to participate. Participants were presented with 12 pairs of simulated MS patient profiles described by 13 clinically relevant factors. We used disaggregated discrete choice experiments to estimate the weight of factors and attributes affecting physicians' decisions when considering treatment selection. Participants were asked to select the ideal candidate for treatment escalation from modest to higher-efficacy therapies. RESULTS: Overall, 229 neurologists completed the study (completion rate: 76.3%). The top 3 weighted factors associated with treatment escalation were: previous relapses (20%), baseline expanded disability status scale [EDSS] (18%), and MRI activity (13%). Patient demographics and desire for pregnancy had a modest influence (≤ 3%). We observed differences in the weight of factors associated with treatment escalation between MS specialists and non-MS specialists. CONCLUSIONS: Our results provide critical information on factors influencing neurologists' treatment decisions and should be applied to continuing medical education strategies.

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.

[Clinical monitoring of multiple sclerosis patients by means of digital technology, a field in the midst of a revolution]. / Monitorización clínica del paciente con esclerosis múltiple a través de la tecnología digital, un campo en plena revolución.

INTRODUCTION: Despite the great advances that have occurred in the diagnosis and treatment of ? multiple sclerosis (MS), few changes have taken place in terms of clinical monitoring. The lack of time and space in clinical practice limits the assessment of invisible symptoms and certain motor symptoms as manual dexterity and walking ability, which have a clear impact on the patient functional situation. OBJECTIVE: To review the potential role of technological tools in the clinical monitoring of MS patients. DEVELOPMENT: A bibliographic search was carried out through PubMed, selecting those studies focused on biosensors and digital tools aimed at evaluating the general functional situation, and specific aspects of the disease or certain functional systems. RESULTS: Different digital tools such as biosensors, mobile or web applications, both for remote and hospital use, self-completed or administered by healthcare personnel, seem to offer a more 'complete and real' picture of the functional situation of patients. Some studies have shown that digital technology could detect subclinical disability progression, which traditional tests, including the EDSS, fail to reflect, favouring the adoption of appropriate therapeutic measures and actions in an early and personalized manner. CONCLUSIONS: Digital tools, capable of collecting detailed and extensive clinical information, could play an important role in decision-making and clinical monitoring of patients with MS.

TITLE: Monitorización clínica del paciente con esclerosis múltiple a través de la tecnología digital, un campo en plena revolución.Introducción. A pesar de los grandes avances acontecidos en el área del diagnóstico y el tratamiento de la esclerosis múltiple (EM), pocos cambios se han gestado respecto al seguimiento clínico. La escasez de tiempo y espacio en la práctica clínica dificulta la valoración de síntomas invisibles y ciertos síntomas motores, como la destreza manual y la capacidad de marcha, que presentan un claro impacto en la situación funcional del paciente. Objetivo. Revisar el papel potencial de las herramientas tecnológicas en la monitorización clínica del paciente con EM. Desarrollo. Se realizó una búsqueda bibliográfica a través de PubMed, seleccionando los estudios centrados en biosensores y herramientas digitales destinadas a la evaluación de la situación funcional general, y de aspectos concretos de la enfermedad o de determinados sistemas funcionales. Resultados. Diferentes herramientas digitales en formato de biosensores, aplicaciones móviles o web, tanto de uso remoto como hospitalario, autocumplimentadas o administradas por el personal sanitario, parecen ofrecer una visión más 'completa y real' de la situación funcional de los pacientes. Algunos estudios han demostrado que la tecnología digital es capaz de detectar la progresión subclínica de la discapacidad, que las pruebas tradicionales, incluyendo la Escala expandida del estado de discapacidad, no consiguen reflejar, lo que favorece la adopción de medidas y acciones terapéuticas apropiadas de forma temprana y personalizada. Conclusiones. Las herramientas digitales, capaces de brindar información clínica amplia y detallada, podrían ocupar un papel importante en la toma de decisiones y el seguimiento clínico del paciente afecto de EM.

Monitorización clínica del paciente con esclerosis múltiple a través de la tecnología digital, un campo en plena revolución / Clinical monitoring of multiple sclerosis patients by means of digital technology, a field in the midst of a revolution

Introducción: A pesar de los grandes avances acontecidos en el área del diagnóstico y el tratamiento de la esclerosis múltiple (EM), pocos cambios se han gestado respecto al seguimiento clínico. La escasez de tiempo y espacio en la práctica clínica dificulta la valoración de síntomas invisibles y ciertos síntomas motores, como la destreza manual y la capacidad de marcha, que presentan un claro impacto en la situación funcional del paciente. Objetivo: Revisar el papel potencial de las herramientas tecnológicas en la monitorización clínica del paciente con EM. Desarrollo: Se realizó una búsqueda bibliográfica a través de PubMed, seleccionando los estudios centrados en biosensores y herramientas digitales destinadas a la evaluación de la situación funcional general, y de aspectos concretos de la enfermedad o de determinados sistemas funcionales. Resultados: Diferentes herramientas digitales en formato de biosensores, aplicaciones móviles o web, tanto de uso remoto como hospitalario, autocumplimentadas o administradas por el personal sanitario, parecen ofrecer una visión más ‘completa y real’ de la situación funcional de los pacientes. Algunos estudios han demostrado que la tecnología digital es capaz de detectar la progresión subclínica de la discapacidad, que las pruebas tradicionales, incluyendo la Escala expandida del estado de discapacidad, no consiguen reflejar, lo que favorece la adopción de medidas y acciones terapéuticas apropiadas de forma temprana y personalizada. Conclusiones: Las herramientas digitales, capaces de brindar información clínica amplia y detallada, podrían ocupar un papel importante en la toma de decisiones y el seguimiento clínico del paciente afecto de EM.(AU)

Introduction: Despite the great advances that have occurred in the diagnosis and treatment of ​ multiple sclerosis (MS), few changes have taken place in terms of clinical monitoring. The lack of time and space in clinical practice limits the assessment of invisible symptoms and certain motor symptoms as manual dexterity and walking ability, which have a clear impact on the patient functional situation.Objective: To review the potential role of technological tools in the clinical monitoring of MS patients. Development: A bibliographic search was carried out through PubMed, selecting those studies focused on biosensors and digital tools aimed at evaluating the general functional situation, and specific aspects of the disease or certain functional systems. Results: Different digital tools such as biosensors, mobile or web applications, both for remote and hospital use, self-completed or administered by healthcare personnel, seem to offer a more ‘complete and real’ picture of the functional situation of patients. Some studies have shown that digital technology could detect subclinical disability progression, which traditional tests, including the EDSS, fail to reflect, favouring the adoption of appropriate therapeutic measures and actions in an early and personalized manner. Conclusions: Digital tools, capable of collecting detailed and extensive clinical information, could play an important role in decision-making and clinical monitoring of patients with MS.(AU)

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.

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

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.(AU)

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

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.(AU)

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.

Long-term safety data from the cladribine tablets clinical development program in multiple sclerosis.

BACKGROUND: Long-term safety data are of particular interest for any newly approved treatment in multiple sclerosis such as cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg), which is approved in Europe and the USA. Here we provide the final report on the integrated analysis of the safety profile of cladribine tablets 3.5 mg/kg from the clinical development program, including final data from the PREMIERE registry. METHODS: Safety data for cladribine tablets 3.5 mg/kg from three previously reported Phase III studies (CLARITY, CLARITY Extension and ORACLE-MS), as well as the prospective, observational PREMIERE registry (which ran from November 2009 to October 2018; consisting of patients who had participated in at least one of the Phase III trials) were combined to provide the Monotherapy Oral cohort. Serious adverse events (SAEs) and predefined SAEs of special interest were recorded. Observation-adjusted incidence rates per 100 patient-years (Adj-AE per 100 PY) were used to assess adverse events (AEs). Standardized incidence ratios for malignancies were calculated in relation to a matched GLOBOCAN reference population, and risk differences (cladribine tablets versus placebo) were estimated. RESULTS: The Monotherapy Oral cohort comprised 923 patients who received cladribine tablets 3.5 mg/kg and 641 patients who received placebo. Overall, the reported number of SAEs was higher in the cladribine tablets 3.5 mg/kg group (133/923 [14.4%] patients with at least 1 SAE), versus the placebo group (68/641 [10.6%] patients with at least 1 SAE). Four patients in the cladribine tablets 3.5 mg/kg group had lymphopenia classified as a serious event (resulting in an Adj-AE of 0.10 per 100 PY) and 2 patients had serious herpes zoster (resulting in an Adj-AE of 0.05 per 100 PY). There were no cases in the corresponding placebo groups. There was no difference between the cladribine tablets 3.5 mg/kg group and placebo in the overall incidence of infections. However herpetic infection AEs occurred more frequently in the cladribine tablets 3.5 mg/kg group (driven primarily by herpes zoster, followed by oral herpes and herpes simplex). Overall, there was a numerical imbalance in malignancy incidence between cladribine tablets 3.5 mg/kg and placebo, with an Adj-AE of 0.26 and 0.12 per 100 PY, respectively; however the difference was not statistically significant. The rate of malignancies observed with cladribine tablets 3.5 mg/kg in the final integrated safety analysis was not different from the expected rate in the matched GLOBOCAN reference population (standardized incidence ratio, 0.88; 95% CI, 0.44-1.69). CONCLUSION: Additional patient-years of observation do not significantly alter the conclusions of earlier interim analyses, and no new major safety findings were identified in this consolidated analysis of safety data of cladribine tablets 3.5 mg/kg monotherapy in patients with relapsing-remitting multiple sclerosis.

[Prevalence and impact of comorbidities in patients with multiple sclerosis]. / Prevalencia e impacto de las comorbilidades en pacientes con esclerosis múltiple.

INTRODUCTION: Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system. In most cases it is characterised by the recurring focal neurological deficit, which may become progressive over time. Given the chronic nature of the disease, patients may present with additional diseases (comorbidities), which affect the natural history of the disease and its treatment in different ways. AIM: To summarise the available evidence regarding the influence of comorbidities on the natural history of multiple sclerosis. DEVELOPMENT: Patients with multiple sclerosis are at greater risk than the general population of developing both acute and chronic comorbidities. It has been shown that comorbidities can delay the diagnosis of multiple sclerosis after clinical onset, increase the rates of relapses and of accumulation of disability. Comorbidities also influence aspects of the choice of treatment and therapy adherence. Finally, comorbidities also increase the mortality rate and reduce the quality of life of patients with multiple sclerosis. CONCLUSIONS: Screening, diagnosis and treatment of comorbidities are a key aspect of caring for patients with multiple sclerosis to improve their long-term prognosis in terms of disability, quality of life and mortality.

TITLE: Prevalencia e impacto de las comorbilidades en pacientes con esclerosis múltiple.Introducción. La esclerosis múltiple es una enfermedad crónica, de origen inflamatorio y degenerativo, del sistema nervioso central. Se caracteriza en la mayoría de los casos por la aparición de manera recurrente de brotes de déficit neurológico focal, que con el tiempo puede tornarse progresivo. Dado el carácter crónico de la enfermedad, los pacientes pueden presentar enfermedades adicionales (comorbilidades), que impactan de diferentes maneras en la historia natural de la enfermedad y en su tratamiento. Objetivo. Resumir la evidencia disponible respecto a la influencia de las comorbilidades en la historia natural de la esclerosis múltiple. Desarrollo. Los pacientes con esclerosis múltiple tienen un riesgo mayor que la población general de desarrollar comorbilidades tanto agudas como crónicas. Se ha demostrado que las comorbilidades pueden retrasar el diagnóstico de esclerosis múltiple después del inicio clínico, incrementar la tasa de brotes y aumentar la tasa de acumulación de la discapacidad. Las comorbilidades también influyen en aspectos relacionados con la elección del tratamiento y la adhesión terapéutica. Finalmente, las comorbilidades también aumentan la tasa de mortalidad y la calidad de vida de los pacientes con esclerosis múltiple. Conclusiones. El cribado, el diagnóstico y el tratamiento de las comorbilidades son un aspecto clave del cuidado de los pacientes con esclerosis múltiple para mejorar su pronóstico a largo plazo en cuanto a discapacidad, calidad de vida y mortalidad.

Optical coherence tomography measures correlate with brain and spinal cord atrophy and multiple sclerosis disease-related disability.

BACKGROUND AND PURPOSE: Both optical coherence tomography (OCT) and magnetic resonance imaging (MRI) volumetric measures have been postulated as potential biomarkers of multiple sclerosis (MS)-related disability. The aim of the study was to investigate the association between OCT and brain volume and spinal cord area (SCA) parameters in patients with relapsing MS and to assess their independent associations with disability. METHODS: This was a cross-sectional analysis of 90 patients with MS who underwent OCT and MRI examination. Values of peripapillary retinal nerve fibre layer (pRNFL), ganglion cell/inner plexiform layer (GCIPL) and inner nuclear layer of eyes without previous optic neuritis were obtained. SCA and brain parenchymal fraction (BPF), grey and white matter fractions were obtained. Multivariable regression analyses were conducted with disability as dependent variable. RESULTS: Lower pRNFL thickness and lower GCIPL volume as well as lower BPF, grey matter fraction and SCA were associated with a longer disease duration and a higher Expanded Disability Status Scale score. Lower pRNFL thickness and GCIPL volumes were associated with lower BPF and SCA. In the multivariable logistic regression analyses, pRNFL thickness and GCIPL volume outperformed MRI in predicting disability. CONCLUSIONS: The OCT measures correlate with brain and spinal cord atrophy and appear more closely associated with disability than MRI volumetric measures.

Value of 3T Susceptibility-Weighted Imaging in the Diagnosis of Multiple Sclerosis.

BACKGROUND AND PURPOSE: Previous studies have suggested that the central vein sign and iron rims are specific features of MS lesions. Using 3T SWI, we aimed to compare the frequency of lesions with central veins and iron rims in patients with clinically isolated syndrome and MS-mimicking disorders and test their diagnostic value in predicting conversion from clinically isolated syndrome to MS. MATERIALS AND METHODS: For each patient, we calculated the number of brain lesions with central veins and iron rims. We then identified a simple rule involving an absolute number of lesions with central veins and iron rims to predict conversion from clinically isolated syndrome to MS. Additionally, we tested the diagnostic performance of central veins and iron rims when combined with evidence of dissemination in space. RESULTS: We included 112 patients with clinically isolated syndrome and 35 patients with MS-mimicking conditions. At follow-up, 94 patients with clinically isolated syndrome developed MS according to the 2017 McDonald criteria. Patients with clinically isolated syndrome had a median of 2 central veins (range, 0-19), while the non-MS group had a median of 1 central vein (range, 0-6). Fifty-six percent of patients who developed MS had ≥1 iron rim, and none of the patients without MS had iron rims. The sensitivity and specificity of finding ≥3 central veins and/or ≥1 iron rim were 70% and 86%, respectively. In combination with evidence of dissemination in space, the 2 imaging markers had higher specificity than dissemination in space and positive findings of oligoclonal bands currently used to support the diagnosis of MS. CONCLUSIONS: A single 3T SWI scan offers valuable diagnostic information, which has the potential to prevent MS misdiagnosis.