Esclerose múltipla: importância do diagnóstico precoce e tratamento adequado

A esclerose múltipla (EM) é uma doença neurológica autoimune, que não tem cura, e que acomete o sistema nervoso central, composto pelo cérebro e a medula espinhal. Atualmente, 2,8 milhões de pessoas em todo o mundo têm EM. Estima-se que no Brasil, cerca de 40 mil pessoas vivem com a doença.

Iniciativas enfermeras. La importancia de tener acceso a una unidad específica para cualquier enfermedad crónica, y más aún degenerativa e impredecible como lo es la esclerosis múltiple, es primordial, necesaria y de derecho / Nursing initiatives. The importance of having access to a specific unit for any chronic disease, and even more degenerative and unpredictable as multiple sclerosis is, is paramount, necessary and right

Hace más de 10 años que comenzó todo con una llamada de teléfono que lo confirmaba: la esclerosis múltiple llegaba a sus vidas.La noticia las inundó de miedos, pero Noelia Martín Pérez tenía una cosa clara: iba a luchar con su hermana en todo lo que hicierafalta. Después de un encuentro que realiza la Asociación Esclerosis Múltiple España al que fueron invitadas, y con la inyección depositivismo y fuerza que recibieron, se le ocurrió crear Nubes solidarias, un proyecto que compagina con su trabajo como enfermeraen el Hospital Gregorio Marañón (Madrid), que consiste en crear y vender complementos en forma de nube para recaudar fondosy destinarlos a la investigación de la esclerosis múltiple. Poco a poco se ha ido solidarizando más gente, haciendo que esta nubesolidaria llegue cada día a un lugar diferente con su arte y sus pulseras. ¡Hablamos con ella!.(AU)

Inverse association between Mediterranean diet and risk of multiple sclerosis.

OBJECTIVE: There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple sclerosis (MS). METHODS: We used a population-based case-control study recruiting incident cases of MS (1953 cases, 3557 controls). Subjects with different dietary habits 5 years prior to MS diagnosis were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Adjustment was made for a large number of environmental and lifestyle habits, including ancestry, smoking, alcohol consumption, body mass index, physical activity, and sun exposure habits. RESULTS: Mediterranean diet was associated with lower risk of developing MS (adjusted OR = 0.54, 95% CI: 0.34-0.86, p = 0.009), compared with Western-style diet. There was no significant association between vegetarian/vegan diet and MS risk (adjusted OR = 0.96, 95% CI: 0.75-1.24, p = 0.976), nor between diet with low glycemic index and MS risk (adjusted OR = 0.93, 95% CI: 0.60-1.42, p = 0.518). CONCLUSIONS: Mediterranean diet may exert a protective influence regarding the risk of subsequently developing MS compared with Western-style diet.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

Protective effect of crocin on cuprizone-induced model of multiple sclerosis in mice.

Crocin is the main bioactive components of the saffron which has positive role in the nervous system; however, its neuroprotective activity is not fully elicited. So, the aim of the current study was to determine effects of the crocin on reflexive motor and anti-depressive behaviors as well as serum and brain tissue antioxidant activities in cuprizone-induced (CPZ) model of multiple sclerosis (MS) mice. Forty male C57BL/6 mice were randomly assigned into 4 groups. Mice in the control group were received normal diet. In group 2, mice received normal diet and orally received crocin (100 mg/kg) 3 times per week for 5 weeks. In group 3, CPZ-induced demyelination was done by chew palate containing 0.2% (w/w) CPZ for 5 weeks. In group 4, mice feed CPZ containing diet and orally received crocin (100 mg/kg) three times per for 5 weeks. After determination of the MS signs, reflexive motor behavior and depressive tests were done. Also, serum and brain tissue antioxidant activity was determined. According to the data, CPZ had negative effects on hind-limb foot angle, hind- and front-limb suspension, surface righting, grip strength, and negative geotaxis while crocin improved it. Co-administration of the CPZ + crocin reversed effect of the CPZ on the reflexive motor behaviors. CPZ increased immobility time in the forced swimming test (FST) and tail suspension test (TST), while co-administration of the CPZ + crocin reversed effect of the CPZ on immobility time. CPZ decreased number of cross in open field test (OFT) and spending time on rotarod, while co-administration of the CPZ + crocin reversed effect of the CPZ. Malondialdehyde (MDA) production increased, and glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant status (TAS) levels decreased in serum and brain tissue of the mice treated with CPZ. Pretreatment with crocin decreased adverse effect of the CPZ on serum and brain tissue antioxidants. These results suggested crocin has protective effect against CPZ-induced MS in mice.

Epstein-Barr virus as a cause of multiple sclerosis: opportunities for prevention and therapy.

Multiple sclerosis is a chronic inflammatory disease of the CNS that results from the interplay between heritable and environmental factors. Mounting evidence from different fields of research supports the pivotal role of the Epstein-Barr virus (EBV) in the development of multiple sclerosis. However, translating this knowledge into clinically actionable information requires a better understanding of the mechanisms linking EBV to pathophysiology. Ongoing research is trying to clarify whether EBV causes neuroinflammation via autoimmunity or antiviral immunity, and if the interaction of EBV with genetic susceptibility to multiple sclerosis can explain why a ubiquitous virus promotes immune dysfunction in susceptible individuals. If EBV also has a role in driving disease activity, the characterisation of this role will help diagnosis, prognosis, and treatment in people with multiple sclerosis. Ongoing clinical trials targeting EBV and new anti-EBV vaccines provide hope for future treatments and preventive interventions.

A process evaluation of an on-line fall prevention and management program for individuals who use wheelchairs or scooters living with multiple sclerosis.

Background: Falls and resulting injury are a significant concern for individuals living with multiple sclerosis (MS) that use a wheelchair and/or scooter to support mobility. Effective fall prevention efforts are vital to support the health, wellbeing, and participation for these individuals. Aims: This study reports the findings from the process evaluation conducted in association with a pilot study evaluating the efficacy of Individualized Reduction of FaLLs-Online (iROLL-O), an online, group fall prevention, and management program specifically designed for community-based people living with multiple sclerosis (pwMS) who are full-time wheelchair or scooter users. Methods: A mixed-methods process evaluation was conducted, with specific attention to the impact of online delivery on intervention implementation, participant satisfaction, and mechanisms of change (MOC). Multiple data sources were utilized, including post-session and post-intervention participant and trainer feedback forms and participant qualitative interview data. Descriptive analysis was conducted using Microsoft Excel. Close-ended questions were analyzed by examining five-point Likert scale responses. Qualitative interview data was explored using thematic analysis. Results: Twelve participants and three trainers (one occupational therapist and two physical therapists) contributed to the study. Online delivery did not compromise session fidelity, which averaged 95%. No significant adaptations to the intervention were made during delivery. Participant satisfaction was high at 4.6/5.0. Post-course Trainer Feedback Forms indicate trainer satisfaction with the group dynamic, ability to address unique group needs, and program content. Reach improved with online delivery as transportation barriers were removed and recruitment from a broader geographic area was enabled. Three themes reflecting key MOC emerged from the analysis: group context, motivation for participant engagement, and the multifaceted nature of the program. The COVID-19 pandemic was identified as a contextual factor impacting community participation. Both participants and trainers identified the group dynamic as a strength. The trainers valued the program's flexibility in allowing them to address individual and/or group-specific fall prevention needs. Conclusion: Feedback from key stakeholders was essential to a meaningful process evaluation. Online delivery supported program implementation, including reach, and resulted in high levels of satisfaction among participants and trainers. Future iterations should aim to uphold the positive group context, recruit, and train skilled interventionists who are licensed as occupational or physical therapists and continue to provide the program's diverse approach to fall prevention and management.

From the prodromal stage of multiple sclerosis to disease prevention.

A prodrome is an early set of signs or symptoms that indicate the onset of a disease before more typical symptoms develop. Prodromal stages are well recognized in some neurological and immune-mediated diseases such as Parkinson disease, schizophrenia, type 1 diabetes mellitus and rheumatoid arthritis. Emerging evidence indicates that a prodromal stage exists in multiple sclerosis (MS), raising the possibility of intervention at this stage to delay or prevent the development of classical MS. However, much remains unclear about the prodromal stage of MS and considerable research is needed to fully characterize the prodrome and develop standardized criteria to reliably identify individuals with prodromal MS who are at high risk of progressing to a diagnosis of MS. In this Roadmap, we draw on work in other diseases to propose a disease framework for MS that incorporates the prodromal stage, and set out key steps and considerations needed in future research to fully characterize the MS prodrome, identify early disease markers and develop standardized criteria that will enable reliable identification of individuals with prodromal MS, thereby facilitating trials of interventions to slow or stop progression beyond the prodrome.

Siponimod Inhibits the Formation of Meningeal Ectopic Lymphoid Tissue in Experimental Autoimmune Encephalomyelitis.

BACKGROUND AND OBJECTIVES: To investigate whether the formation or retention of meningeal ectopic lymphoid tissue (mELT) can be inhibited by the sphingosine 1-phosphate receptor 1,5 modulator siponimod (BAF312) in a murine model of multiple sclerosis (MS). METHODS: A murine spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model, featuring meningeal inflammatory infiltrates resembling those in MS, was used. To prevent or treat EAE, siponimod was administered daily starting either before EAE onset or at peak of disease. The extent and cellular composition of mELT, the spinal cord parenchyma, and the spleen was assessed by histology and immunohistochemistry. RESULTS: Siponimod, when applied before disease onset, ameliorated EAE. This effect was also present, although less prominent, when treatment started at peak of disease. Treatment with siponimod resulted in a strong reduction of the extent of mELT in both treatment paradigms. Both B and T cells were diminished in the meningeal compartment. DISCUSSION: Beneficial effects on the disease course correlated with a reduction in mELT, suggesting that inhibition of mELT may be an additional mechanism of action of siponimod in the treatment of EAE. Further studies are needed to establish causality and confirm this observation in MS.

Nobiletin attenuates inflammation via modulating proinflammatory and antiinflammatory cytokine expressions in an autoimmune encephalomyelitis mouse model.

The aim of this study is to investigate the potential preventive and therapeutic effects of nobiletin by evaluating the expression of cytokines associated with inflammatory reactions in an autoimmune encephalomyelitis mouse model. A total of 60 male C57BL/6 mice aged between 8 and 10 weeks were used. Mice were divided into six groups (n = 10 mice per group): control, EAE, low-prophylaxis, high-prophylaxis, low-treatment and high-treatment. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG) and pertussis toxin. Nobiletin was administered in low (25 mg/kg) and high (50 mg/kg) doses, intraperitoneally. The prophylactic and therapeutic effects of nobiletin on brain tissue and spinal cord were evaluated by expression of interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), IL-6, IL-10 and transforming growth factor-beta (TGF-ß) using immunohistochemistry and real-time polymerase chain reaction (RT-PCR). Prophylactic and therapeutic use of nobiletin inhibited EAE-induced increase of TNF-α, IL-1ß and IL-6 activities to alleviate inflammatory response in brain and spinal cord. Moreover, nobiletin supplement dramatically increased the IL-10, TGF-ß and IFNγ expressions in prophylaxis and treatment groups compared with the EAE group in the brain and spinal cord. The results obtained from this study show that prophylactic and therapeutic nobiletin modulates expressions of proinflammatory and antiinflammatory cytokines in brain and spinal cord dose-dependent manner in EAE model. These data demonstrates that nobiletin has a potential to attenuate inflammation in EAE mouse model. These experimental findings need to be supported by clinical studies.

Dietary fish intake and the risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

Objectives: There is some inconclusive evidence for the role of fish consumption in susceptibility to multiple sclerosis (MS). The present study aimed to systematically review and determine the association between dietary fish intake and risk of MS.Methods: A systematic search with related keywords was carried out in PubMed-MEDLIN, Scopus-EMBASE, and OVID-MEDLINE from inception up to September 2019 to find observational studies that evaluated the association between dietary fish intake and the risk of MS. Random effect and subgroup analyses were performed to calculate pooled estimates at 95% CIs.Results: Six articles met the inclusion criteria for systematic review and meta-analysis. The results of this study indicated that the consumption of fish decreases the risk of MS [OR (95% CIs): 0.77 (0.64, 0.92); p-value = 0.004; I2 = 54.7%] compared with controls.Discussion: Dietary intake of at least 0.5 servings of fish per week during adolescence and after might reduce the risk of MS; however, further studies are required to prove this preventive effect.

The Effects of Vitamin D on Immune System and Inflammatory Diseases.

Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.

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)

[The corona pandemic and multiple sclerosis: vaccinations and their implications for patients-Part 2: vaccine technologies]. / Die Corona-Pandemie und Multiple Sklerose: Impfungen und deren Implikationen für Patienten ­ Teil 2: Impfstofftechnologien.

Along with the challenges posed by the globally circulating COVID-19 pandemic, there have been some epochal advances in the field of vaccine technologies. In addition to the traditionally used dead, live and protein-based vaccines, vector-based and gene-based vaccines gained enormous attention in the course of this health crisis. The aim of this article is to provide an overview of multiple sclerosis (MS) and vaccination, recent advances in the SARS-CoV­2 vaccine landscape as well as a detailed discussion of the various vaccine technologies. Finally, clear recommendations in the context of disease-modifying treatment and vaccination in MS are highlighted.

Vitamin D-independent benefits of safe sunlight exposure.

This review examines the beneficial effects of ultraviolet radiation on systemic autoimmune diseases, including multiple sclerosis and type I diabetes, where the epidemiological evidence for the vitamin D-independent effects of sunlight is most apparent. Ultraviolet radiation, in addition to its role in the synthesis of vitamin D, stimulates anti-inflammatory pathways, alters the composition of dendritic cells, T cells, and T regulatory cells, and induces nitric oxide synthase and heme oxygenase metabolic pathways, which may directly or indirectly mitigate disease progression and susceptibility. Recent work has also explored how the immune-modulating functions of ultraviolet radiation affect type II diabetes, cancer, and the current global pandemic caused by SARS-CoV-2. These diseases are particularly important amidst global changes in lifestyle that result in unhealthy eating, increased sedentary habits, and alcohol and tobacco consumption. Compelling epidemiological data shows increased ultraviolet radiation associated with reduced rates of certain cancers, such as colorectal cancer, breast cancer, non-Hodgkins lymphoma, and ultraviolet radiation exposure correlated with susceptibility and mortality rates of COVID-19. Therefore, understanding the effects of ultraviolet radiation on both vitamin D-dependent and -independent pathways is necessary to understand how they influence the course of many human diseases.

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)

Anti-CD20 Depletes Meningeal B Cells but Does Not Halt the Formation of Meningeal Ectopic Lymphoid Tissue.

OBJECTIVE: To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (ɑCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS). METHODS: We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in MS. ɑCD20 mAbs were administered in either a preventive or a treatment regimen. The extent and cellular composition of mELT was assessed by histology and immunohistochemistry. RESULTS: ɑCD20 mAb, applied in a paradigm to either prevent or treat EAE, did not alter the disease course in either condition. However, ɑCD20 mAb depleted virtually all B cells from the meningeal compartment but failed to prevent the formation of mELT altogether. Because of the absence of B cells, mELT was less densely populated with immune cells and the cellular composition was changed, with increased neutrophil granulocytes. CONCLUSIONS: These results demonstrate that, in CNS autoimmune disease, meningeal inflammatory infiltrates may form and persist in the absence of B cells. Together with the finding that ɑCD20 mAb does not ameliorate spontaneous chronic EAE with mELT, our data suggest that mELT may have yet unknown capacities that are independent of B cells and contribute to CNS autoimmunity.