Baseline serum neurofilament light chain levels differentiate aggressive from benign forms of relapsing-remitting multiple sclerosis: a 20-year follow-up cohort.

BACKGROUND AND OBJECTIVES: Serum biomarkers are emerging as useful prognostic tools for multiple sclerosis (MS); however, long-term studies are lacking. We aimed to evaluate the long-term prognostic value of the serum levels of neurofilament light chain (NfL), total tau, glial fibrillary acidic protein (GFAP), and chitinase 3-like-1 (CHI3L1) measured close to the time of MS onset. METHODS: In this retrospective, exploratory, observational, case and controls study, patients with relapsing-remitting MS (RRMS) with available baseline serum samples and prospectively follow-up in our MS unit for a long time were selected based on their clinical evolution to form two groups: (1) a benign RRMS (bRRMS) group, defined as patients with an Expanded Disability Status Scale (EDSS) score of ≤ 3 at ≥ 10 years of follow-up; (2) an aggressive RRMS (aRRMS) group, defined as patients with an EDSS score of ≥ 6 at ≤ 15 years of follow-up. An age-matched healthy control (HC) group was selected. NfL, total tau, and GFAP serum levels were quantified using a single-molecule array (SIMOA), and CHI3L1 was quantified using ELISA. RESULTS: Thirty-one patients with bRRMS, 19 with aRRMS, and 10 HC were included. The median follow-up time from sample collection was 17.74 years (interquartile range, 14.60-20.37). Bivariate and multivariate analyses revealed significantly higher NfL and GFAP levels in the aRRMS group than in the bRRMS group. A receiver operating characteristic curve analysis identified serum NfL level as the most efficient marker for distinguishing aRRMS from bRRMS. DISCUSSION: This proof-of-concept study comparing benign and aggressive RRMS groups reinforces the potential role of baseline NfL serum levels as a promising long-term disability prognostic marker. In contrast, serum GFAP, total tau, and CHI3L1 levels demonstrated a lower or no ability to differentiate between the long-term outcomes of RRMS.

Kappa free light chains index in multiple sclerosis very long-term prognosis.

Introduction: The role of the kappa-free light chain (kFLC) in the diagnosis of multiple sclerosis (MS) and, to a lesser extent, its role as a medium-term prognostic marker have been extensively studied. This study aimed to explore its potential as a long-term prognostic marker for MS. Methods: We performed an exploratory retrospective observational study by selecting patients systemically followed up in our MS unit with available cerebrospinal fluid and serum samples at the time of initial evaluation. Two groups were defined: benign MS (bMS), defined as patients with Expanded Disability Status Scale (EDSS) ≤ 3 at 10 years of follow-up, and aggressive MS (aMS), defined as patients with EDSS ≥ 6 at 15 years of follow-up. Clinical variables were collected, and the immunoglobulin G (IgG) index, kFLC index, and oligoclonal bands (OCB) were determined for all patients and compared between the groups. Results: Twenty bMS and 15 aMS patients were included in this study. Sixty percent (21/35) were female, and the mean age at the time of the first symptom was 31.5 ± 9.45 years, with no statistical differences between groups. Median follow-up time was 19.8 years (Interquartile range, IQR 15.9-24.6). The median EDSS scores at the last follow-up were 1.5 and 7.5 in the bMS and the aMS group, respectively. No statistically significant differences were found in the kFLC index between the two groups (136.6 vs. 140.27, p=0.59). The IgG index was positive in 62.9% of patients (55% bMS vs. 73.3% aMS, p>0.05), and OCB was positive in 88.6% (90% bMS vs. 86.7% aMS, p>0.05). A significant positive correlation was found between IgG and kFLC indices (rs = 0.85, p<0.001). Conclusion: Given the absence of differences between the two groups with opposite disease courses, it is unlikely that the kFLC index is a reliable and powerful marker of long-term prognosis in MS.

Natalizumab continuation versus switching to ocrelizumab after PML risk stratification in RRMS patients: a natural experiment.

BACKGROUND: Natalizumab (NTZ) and ocrelizumab (OCR) can be used for the treatment of relapsing-remitting multiple sclerosis (RRMS). In patients treated with NTZ, screening for JC virus (JCV) is mandatory, and a positive serology usually requires a change in treatment after 2 years. In this study, JCV serology was used as a natural experiment to pseudo-randomize patients into NTZ continuation or OCR. METHODS: An observational analysis of patients who had received NTZ for at least 2 years and were either changed to OCR or maintained on NTZ, depending on JCV serology status, was performed. A stratification moment (STRm) was established when patients were pseudo-randomized to either arm (NTZ continuation if JCV negativity, or change to OCR if JCV positivity). Primary endpoints include time to first relapse and presence of relapses after STRm and OCR initiation. Secondary endpoints include clinical and radiological outcomes after 1 year. RESULTS: Of the 67 patients included, 40 continued on NTZ (60%) and 27 were changed to OCR (40%). Baseline characteristics were similar. Time to first relapse was not significantly different. Ten patients in the JCV + OCR arm presented a relapse after STRm (37%), four during the washout period, and 13 patients in the JCV-NTZ arm (32.5%, p = 0.701). No differences in secondary endpoints were detected in the first year after STRm. CONCLUSIONS: The JCV status can be used as a natural experiment to compare treatment arms with a low selection bias. In our study, switching to OCR versus NTZ continuation led to similar disease activity outcomes.

Influence of Cardiovascular Risk Factors in Early Relapsing-Remitting Multiple Sclerosis: A Retrospective Analysis.

INTRODUCTION: Prior studies have suggested that cardiovascular risk factors (CVRFs) can affect the prognosis of multiple sclerosis (MS). The aim of this study was to assess if CVRFs affect the early course of MS. METHODS: A retrospective observational study was performed, including patients diagnosed with relapsing-remitting MS (RRMS) from 2010 to 2020, with at least 2 years of disease and 6 months follow-up. Age at onset, disease duration, number of relapses, time to confirmed Expanded Disability Status Scale (EDSS) 3.0 and 6.0, and time to secondary progressive MS (SPMS) were collected. Presence and date at onset of hypertension (HT), diabetes mellitus (DM), high low-density lipoprotein cholesterol (LDLc), and smoking during the study period were collected. The primary objective was to assess if CVRFs at the onset of MS are associated with lower time to EDSS 3.0, time to EDSS 6.0, and time to SPMS, using bivariate and multivariate analysis. RESULTS: 281 RRMS patients were included; median age at onset was 33 (IQR 26-39); 69.4% were female. Median EDSS at onset was 1.5 (IQR 1-2.5). Nine patients reached SPMS; 24 patients were diagnosed with HT, 9 with DM, 109 with high LDLc, and 123 were smokers during follow-up. No statistically significant association was found between the presence of CVRF at MS onset and the mentioned clinical outcomes during the MS course. CONCLUSION: No association was found between CVRFs and the early course of MS in our cohort.

The age at onset of relapsing-remitting multiple sclerosis has increased over the last five decades.

BACKGROUND: Patients with relapsing-remitting multiple sclerosis (RRMS) most commonly experience their first symptoms between 20 and 40 years of age. The objective of this study was to investigate how the age at which the first symptoms of RRMS occur has changed over the past decades. METHODS: Patients who were followed up in our unit after an initial diagnosis of RRMS using the Poser or McDonald criteria and who experienced their first symptoms between January 1970 and December 2019 were included in the study. The cohort was divided into five groups according to the decade in which the first symptoms appeared. The age at disease onset was compared across decades. Changes in age were also determined after excluding patients with early-onset disease (<18 years of age) and those with late-onset disease (>50 years of age) to avoid bias. RESULTS: The cohort included 1,622 patients with RRMS, 67.6% of whom were women. Among them, 5.9% and 4% had early-onset and late-onset disease, respectively. The mean age ± standard deviation at onset was 31.11 ± 9.82 years, with no differences between men and women. The mean ages at onset were 23.79 ± 10.19 years between 1970 and 1979, 27.86 ± 9.22 years between 1980 and 1989, 30.07 ± 9.32 years between 1990 and 1999, 32.12 ± 9.47 between 2000 and 2009, and 34.28 ± 9.83 years between 2010 and 2019. The ages at disease onset were progressively higher in the later decades; this trend was statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.264 and R2 of 0.070 (p < 0.001). The results were similar when analysing men and women separately. We conducted an analysis of 1,460 patients (mean age at onset: 31.10 ± 7.99 years), after excluding patients with early-onset and late-onset disease. In this specific subgroup, the mean ages at disease onset were 28.38 ± 8.17 years between 1970 and 1979, 29.22 ± 7.51 years between 1980 and 1989, 30.06 ± 8.02 years between 1990 and 1999, 31.46 ± 7.77 years between 2000 and 2009, and 33.37 ± 7.97 years between 2010 and 2019. The trend was also statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.193 and R2 of 0.037 (p < 0.001). CONCLUSION: Our data showed that the age at RRMS onset has increased over the past decades.

Impact of Neuromyelitis Optica Spectrum Disorder on Quality of Life from the Patients' Perspective: An Observational Cross-Sectional Study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. METHODS: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis. RESULTS: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29. CONCLUSION: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions.

Disease modifying therapy switching in relapsing multiple sclerosis: A Delphi consensus of the demyelinating expert group of the Spanish society of neurology.

BACKGROUND: The increase in available disease modifying therapies (DMTs) for multiple sclerosis has led to greater emphasis on improving treatment sequencing paradigms. This article summarises the opinions from a panel of 25 experts on treatment switching approaches in relapsing multiple sclerosis (RMS). METHODS: A modified Delphi consensus process was carried out to develop clinically relevant statements for aiding treatment decisions in patients with RMS between the 16th January and the 9th October 2019. A sub-group of two experts (core group) carried out an extensive review of the literature and formulated 106 statements for the expert panel to evaluate. RESULTS: From a total number of 106 statements that were submitted to the expert panel for critical evaluation, consensus (at least 80% of the panelists agreed) was reached on 99 of them. These statements cover treatment objectives, reasons for DMT switching, suboptimal response criteria, strategies for treatment change and washout periods. CONCLUSION: The agreed statements provide up-to-date guidance on DMT sequencing for optimal patient management.

Cognitive Performance and Health-Related Quality of Life in Patients with Neuromyelitis Optica Spectrum Disorder.

Background: The frequency of cognitive impairment (CI) reported in neuromyelitis optica spectrum disorder (NMOSD) is highly variable, and its relationship with demographic and clinical characteristics is poorly understood. We aimed to describe the cognitive profile of NMOSD patients, and to analyse the cognitive differences according to their serostatus; furthermore, we aimed to assess the relationship between cognition, demographic and clinical characteristics, and other aspects linked to health-related quality of life (HRQoL). Methods: This cross-sectional study included 41 patients (median age, 44 years; 85% women) from 13 Spanish centres. Demographic and clinical characteristics were collected along with a cognitive z-score (Rao's Battery) and HRQoL patient-centred measures, and their relationship was explored using linear regression. We used the Akaike information criterion to model which characteristics were associated with cognition. Results: Fourteen patients (34%) had CI, and the most affected cognitive domain was visual memory. Cognition was similar in AQP4-IgG-positive and -negative patients. Gender, mood, fatigue, satisfaction with life, and perception of stigma were associated with cognitive performance (adjusted R2 = 0.396, p < 0.001). Conclusions: The results highlight the presence of CI and its impact on HRQoL in NMOSD patients. Cognitive and psychological assessments may be crucial to achieve a holistic approach in patient care.

Cost associated with a relapse-free patient in multiple sclerosis: A real-world health indicator.

BACKGROUND: The efficacy and safety of disease-modifying therapies (DMTs) in multiple sclerosis (MS) are well known; however, owing to their high costs, determining real-world outcomes is essential to evaluate the cost-effectiveness of different therapeutic strategies. This study aimed to investigate the variability in the annual cost of DMTs associated with a relapse-free patient in a representative population cohort of relapsing-remitting MS (RRMS), and whether this could serve as an appropriate health indicator. METHODS: We analyzed the patients followed up in our MS clinic during the years 2016 and 2019, and selected patients belonging to our health district diagnosed with RRMS. The treatment cost associated with a relapse-free patient was the ratio between the total cost of DMTs and the number of relapse-free patients, treated and not treated, during the year of the study. RESULTS: A total of 158 patients with RRMS in 2016 and 183 in 2019 were included in our study. In 2016, 101 patients with RRMS (63.9%) received treatment with DMTs and 120 patients (75.9%) remained relapse-free. The mean cost of DMTs per patient in 2016 was €7414.3 (95% confidence interval [CI]: 6325.2-8503.4) considering all the patients (treated and not treated). In 2019, 126 patients (68.9%) received DMTs and 151 patients (82.5%) remained relapse-free. The mean cost of DMTs per patient in 2019 was €6985.4 (95% CI: 5986.9-7983.9) considering all the patients. The cost per year of DMTs to achieve a relapse-free patient was €9762.2 in 2016 and €8465.8 in 2019. CONCLUSIONS: The treatment cost per year to achieve a relapse-free patient was stable during successive measurements in the same population. Therefore, it may be considered a good real-world health indicator for patients with RRMS treated with DMTs.

Dynamics and Predictors of Cognitive Impairment along the Disease Course in Multiple Sclerosis.

(1) Background: The evolution and predictors of cognitive impairment (CI) in multiple sclerosis (MS) are poorly understood. We aimed to define the temporal dynamics of cognition throughout the disease course and identify clinical and neuroimaging measures that predict CI. (2) Methods: This paper features a longitudinal study with 212 patients who underwent several cognitive examinations at different time points. Dynamics of cognition were assessed using mixed-effects linear spline models. Machine learning techniques were used to identify which baseline demographic, clinical, and neuroimaging measures best predicted CI. (3) Results: In the first 5 years of MS, we detected an increase in the z-scores of global cognition, verbal memory, and information processing speed, which was followed by a decline in global cognition and memory (p < 0.05) between years 5 and 15. From 15 to 30 years of disease onset, cognitive decline continued, affecting global cognition and verbal memory. The baseline measures that best predicted CI were education, disease severity, lesion burden, and hippocampus and anterior cingulate cortex volume. (4) Conclusions: In MS, cognition deteriorates 5 years after disease onset, declining steadily over the next 25 years and more markedly affecting verbal memory. Education, disease severity, lesion burden, and volume of limbic structures predict future CI and may be helpful when identifying at-risk patients.

Quantifying the patient´s perspective in neuromyelitis optica spectrum disorder: Psychometric properties of the SymptoMScreen questionnaire.

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

Perception of Stigma in Patients with Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman's rank correlation. RESULTS: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p<0.0001) and psychological (rho=0.608, p<0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p<0.0001), MOS-PES score (rho= 0.457, p<0.0001), and D-FIS score (rho=0.556, p<0.0001). CONCLUSION: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge.

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

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:l Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available

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

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

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

La reunión Post-ECTRIMS se celebró por undécimo año consecutivo el pasado octubre de 2018 en Madrid, con el objetivo de analizar los avances en esclerosis múltiple destacados en el último congreso anual ECTRIMS. Fruto de esta reunión, formada por los líderes de opinión en esclerosis múltiple de ámbito nacional, se presentan dos artículos de revisión. En esta segunda parte, se incluye el creciente número de evidencias que confirman la seguridad de la exposición a los tratamientos modificadores de la enfermedad en mujeres que planifican un embarazo, y el efecto beneficioso de la lactancia, siempre y cuando la enfermedad no esté muy activa. Se abordan los datos que muestran cómo la aplicación de los criterios de McDonald de 2017 en población pediátrica ha mejorado considerablemente el diagnóstico en comparación con los criterios anteriores. En cuanto a la esclerosis múltiple progresiva, los resultados de los fármacos neuroprotectores son poco concluyentes, pero se proponen biomarcadores para mejorar la evaluación de la respuesta terapéutica. Los estudios sobre tratamientos de reparación de la mielina sugieren que la remielinización en la esclerosis múltiple es posible. De igual manera, se exponen indicios favorables sobre el trasplante de células madre hematopoyéticas, siempre que se seleccione adecuadamente a los pacientes. Por otro lado, se revisan las similitudes y diferencias de las recomendaciones de las nuevas guías de práctica clínica publicadas. Por último, los resultados positivos de la rehabilitación cognitiva y motora con el uso de las nuevas tecnologías vaticinan la incorporación sistemática de estas herramientas en el tratamiento de la enfermedad en un futuro próximo

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

Revisión de las novedades presentadas en el congreso ECTRIMS 2018: XI Reunión Post-ECTRIMS (I) / Review of the novelties presented at the 2018 ECTRIMS Congress: 11th Post-ECTRIMS Meeting (I)

La reunión Post-ECTRIMS es un encuentro emblemático en España que persigue revisar y difundir los principales avances en esclerosis múltiple presentados en el congreso anual ECTRIMS. En octubre de 2018, la reunión Post-ECTRIMS celebró en Madrid su undécima edición, contando con los mayores expertos de ámbito nacional en esclerosis múltiple. Como resultado de esta reunión, se presentan dos artículos donde se recogen las novedades más destacadas en la misma. En esta primera parte se incluyen los últimos resultados sobre la influencia de los factores de riesgo modificables y no modificables en la esclerosis múltiple, destacando los progresos realizados en el ámbito genético, donde el descubrimiento de genes asociados a la esclerosis múltiple ha aumentado exponencialmente. Se aborda la complejidad del sistema inmune y se realizan algunas aportaciones sobre los mecanismos de autoinmunidad, en los que se observan relaciones bidireccionales entre las células inmunes y las células residentes del sistema nervioso central, como la microglía y los astrocitos. Los biomarcadores, tanto en suero y líquido cefalorraquídeo como de imagen, ganan cada vez más atención por su papel actual, y sobre todo potencial, en el diagnóstico y pronóstico de la enfermedad y en la evaluación de la eficacia de los tratamientos. Por último, se presentan las observaciones realizadas respecto a los cambios en la conectividad estructural y funcional en los pacientes y su relación con las alteraciones clínicas

The Post-ECTRIMS Meeting is an emblematic event in Spain which seeks to review and disseminate the main advances in multiple sclerosis presented at the ECTRIMS annual congress. In October 2018, the eleventh Post-ECTRIMS meeting was held in Madrid and was attended by the country’s leading experts in multiple sclerosis. As a result of this meeting, we present two articles which outline the most interesting novelties discussed there. This first part includes the latest results obtained regarding the influence of modifiable and non-modifiable risk factors in multiple sclerosis, with emphasis on the progress made in the field of genetics, where the discovery of genes associated with multiple sclerosis has increased exponentially. The complexity of the immune system is addressed and some contributions are made on autoimmunity mechanisms, in which bidirectional relations are observed between immune cells and cells residing in the central nervous system, such as microglial cells and astrocytes. Biomarkers, both in serum and cerebrospinal fluid as well as in imaging, are gaining more and more attention due to their current and, above all, potential role in the diagnosis and prognosis of the disease and in the evaluation of the efficacy of treatments. Finally, the observations made regarding changes in structural and functional connectivity in patients and their relationship with clinical alterations are presented

Revisión de las novedades del Congreso ECTRIMS 2017, presentadas en la X Reunión Post-ECTRIMS (II) / Review of the novelties from the 2017 ECTRIMS Congress, presented at the 10th Post-ECTRIMS Meeting (II)

La reunión Post-ECTRIMS es una reunión emblemática en el ámbito de la esclerosis múltiple en España, con el claro objetivo de analizar, de la mano de reconocidos neurólogos especialistas nacionales, los principales avances en esclerosis múltiple y revisar los temas más importantes del congreso ECTRIMS. En noviembre de 2017, la reunión Post-ECTRIMS celebro su décima edición, y se ha consolidado como un importante foro de encuentro de expertos en nuestro país para favorecer la comunicación, establecer sinergias, y promover y potenciar la investigación para mejorar, en última instancia, el pronóstico y la calidad de vida de los pacientes con esclerosis múltiple. En esta segunda parte se abordan las diferentes estrategias para el manejo de los pacientes con enfermedad avanzada y la seguridad de la terapia en esclerosis múltiple, y se resaltan las áreas que requieren una mayor evidencia científica y clínica. La esclerosis múltiple en la población pediátrica y el envejecimiento en la enfermedad cobran especial importancia en esta edición, remarcando la necesidad del desarrollo de estudios colaborativos y de una mayor concienciación de los especialistas en la detección y el manejo de las comorbilidades en la esclerosis múltiple

The Post-ECTRIMS Meeting is an emblematic event in the field of multiple sclerosis in Spain. Its chief aim is bring together the country’s leading specialist neurologists to analyse the main advances made in multiple sclerosis and to review the most important topics addressed at the ECTRIMS Congress. The tenth Post-ECTRIMS Meeting was held in November 2017. Over the years this event has firmly established itself as an important meeting point where experts from all over the country get together to foster communication, establish synergies and promote and enhance research ultimately aimed at improving the prognosis and quality of life of patients with multiple sclerosis. This second part addresses the different strategies for the management of patients in advanced stages of the disease and the safety of therapy in multiple sclerosis. Likewise, attention is also drawn to the areas that require further scientific and clinical evidence. In this edition, particular importance is given to multiple sclerosis in the paediatric population and ageing in the disease. At the same time emphasis is placed on the need to conduct collaborative studies and to foster greater awareness among specialists regarding the detection and management of the comorbidities in multiple sclerosis

Revisión de las novedades del Congreso ECTRIMS 2017, presentadas en la X Reunión Post-ECTRIMS (I) / Review of the novelties from the 2017 ECTRIMS Congress, presented at the 10th Post-ECTRIMS Meeting (I)

La reunión Post-ECTRIMS es una reunión emblemática en el ámbito de la esclerosis múltiple en España, con el claro objetivo de analizar, de la mano de reconocidos neurólogos especialistas nacionales, los principales avances en esclerosis múltiple y revisar los temas más importantes del congreso ECTRIMS. En noviembre de 2017, la reunión Post-ECTRIMS celebró su décima edición, y se ha consolidado como un importante foro de encuentro de expertos en nuestro país para favorecer la comunicación, establecer sinergias, y promover y potenciar la investigación para mejorar, en última instancia, el pronóstico y la calidad de vida de los pacientes con esclerosis múltiple. En esta primera parte se avanza la publicación de las nuevas guías clínicas europea y americana para el uso de los tratamientos modificadores de la enfermedad, y los nuevos criterios diagnósticos. Se discuten las estrategias para el seguimiento de los pacientes tratados con terapias modificadoras de la enfermedad, se revisan la atrofia cerebral y los biomarcadores de neurodegeneración y neuroinflamación, y se analiza el papel de la neuroglía en la patogenia y el tratamiento. Se hace un recorrido por la historia natural de la enfermedad, con la evidencia que aportan los registros, y nos adelantamos al futuro gracias a los avances en genética e inmunología

The Post-ECTRIMS Meeting is an emblematic event in the field of multiple sclerosis in Spain. Its chief aim is bring together the country’s leading specialist neurologists to analyse the main advances made in multiple sclerosis and to review the most important topics addressed at the ECTRIMS Congress. The tenth Post-ECTRIMS Meeting was held in November 2017. Over the years this event has firmly established itself as an important meeting point where experts from all over the country get together to foster communication, establish synergies and promote and enhance research ultimately aimed at improving the prognosis and quality of life of patients with multiple sclerosis. This first part reports on the publication of the new European and American clinical guidelines on the use of disease-modifying treatments and the new diagnostic criteria. It also discusses the strategies for following up patients treated with disease-modifying therapies, reviews cerebral atrophy and biomarkers of neurodegeneration and neuroinflammation, and analyses the role of neuroglia in pathogenesis and treatment. The study examines the natural history of the disease, with the evidence provided by registers, and we anticipate the future thanks to the progress being made in genetics and immunology

Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates.

BACKGROUND: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. OBJECTIVES: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. METHODS: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006-1 January 2016 and prevalence for the date 1 January 2016. RESULTS: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10-76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5-fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40-59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. CONCLUSION: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification.