ESCLEROSE MÚLTIPLA - ABORDAGENS DIAGNÓSTICAS E TERAPÊUTICAS: UMA REVISÃO BIBLIOGRÁFICA

Introduction: Multiple sclerosis (MS) is a progressive disease of the central nervous system with increasing global prevalence, representing a challenge for patients and health professionals. This study aims to address recent diagnostic and therapeutic strategies to improve the management of MS. Objective: To provide a comprehensive overview of diagnostic and therapeutic approaches to MS. Methods: A bibliographic review of the last 15 years was carried out in electronic databases, using specific inclusion criteria. Fifteen articles were selected after evaluating titles and abstracts. Results and Discussion: The increase in the incidence of MS globally and advances in diagnosis, including the role of magnetic resonance imaging and biomarkers, were highlighted. Conventional and emerging therapies were also addressed, emphasizing the importance of individualizing treatment and a multidisciplinary approach. Conclusion: Ongoing research and clinical trials are essential to fill knowledge gaps. A patient-centered approach, combined with scientific advances, promises to improve quality of life and clinical outcomes in MS.Introducción: La esclerosis múltiple (EM) es una enfermedad progresiva del sistema nervioso central con una prevalencia mundial cada vez mayor, lo que representa un reto para los pacientes y los profesionales sanitarios. Este estudio pretende abordar las estrategias diagnósticas y terapéuticas recientes para mejorar el manejo de la EM. Objetivo: Proporcionar una visión global de los enfoques diagnósticos y terapéuticos de la EM. Métodos: Se realizó una revisión bibliográfica de los últimos 15 años en bases de datos electrónicas, utilizando criterios de inclusión específicos. Se seleccionaron 15 artículos tras evaluar títulos y resúmenes. Resultados y discusión: Se destacaron el aumento de la incidencia de la EM en todo el mundo y los avances en el diagnóstico, incluido el papel de la resonancia magnética y los biomarcadores. También se abordaron las terapias convencionales y emergentes, haciendo hincapié en la importancia de un tratamiento individualizado y un enfoque multidisciplinar. Conclusión: La investigación y los ensayos clínicos en curso son esenciales para colmar las lagunas de conocimiento. Un enfoque centrado en el paciente, combinado con los avances científicos, promete mejorar la calidad de vida y los resultados clínicos en la EM.Introdução: A esclerose múltipla (EM) é uma doença progressiva do sistema nervoso central com crescente prevalência global, representando um desafio para pacientes e profissionais de saúde. Este estudo visa abordar as recentes estratégias diagnósticas e terapêuticas para melhorar o manejo da EM. Objetivo: Fornecer uma visão abrangente das abordagens diagnósticas e terapêuticas da EM. Métodos: Realizou-se uma revisão bibliográfica dos últimos 15 anos em bases de dados eletrônicas, utilizando critérios de inclusão específicos. Quinze artigos foram selecionados após avaliação de títulos e resumos. Resultados e Discussão: Destacou-se o aumento da incidência da EM globalmente e os avanços no diagnóstico, incluindo o papel da ressonância magnética e biomarcadores. Abordaram-se também as terapias convencionais e emergentes, enfatizando a importância da individualização do tratamento e da abordagem multidisciplinar. Conclusão: A pesquisa contínua e ensaios clínicos são essenciais para preencher lacunas de conhecimento. A abordagem centrada no paciente, combinada com avanços científicos, promete melhorar a qualidade de vida e os resultados clínicos na EM.Introdução: A esclerose múltipla (EM) é uma doença progressiva do sistema nervoso central com crescente prevalência global, representando um desafio para pacientes e profissionais de saúde. Este estudo visa abordar as recentes estratégias diagnósticas e terapêuticas para melhorar o manejo da EM. Objetivo: Fornecer uma visão abrangente das abordagens diagnósticas e terapêuticas da EM. Métodos: Realizou-se uma revisão bibliográfica dos últimos 15 anos em bases de dados eletrônicas, utilizando critérios de inclusão específicos. Quinze artigos foram selecionados após avaliação de títulos e resumos. Resultados e Discussão: Destacou-se o aumento da incidência da EM globalmente e os avanços no diagnóstico, incluindo o papel da ressonância magnética e biomarcadores. Abordaram-se também as terapias convencionais e emergentes, enfatizando a importância da individualização do tratamento e da abordagem multidisciplinar. Conclusão: A pesquisa contínua e ensaios clínicos são essenciais para preencher lacunas de conhecimento. A abordagem centrada no paciente, combinada com avanços científicos, promete melhorar a qualidade de vida e os resultados clínicos na EM

Long-COVID Cognitive Impairments and Reproductive Hormone Deficits in Men May Stem from GnRH Neuronal Death

Background: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. Methods: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. Findings: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. Interpretation: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups

Long-term high-protein diet intake reverts weight gain and attenuates metabolic dysfunction on high-sucrose-fed adult rats

Abstract Background Consumption of added sugars has been considered a worldwide public health concern by its association with metabolic syndrome and its comorbidities. Meanwhile, current studies have suggested high-protein diets to promote weight loss and improved metabolic outcomes. Thus, this study aimed to investigate the effects of long-term high-protein diet (HPD, 34.3% protein) intake on high-sucrose-fed rats. Methods Weaned male Wistar rats were randomized into two groups: rats fed a standard chow (CT/CT, 10% sucrose) or rats fed a high-sucrose diet (HSD, 25% sucrose) for a 20-week observational period. Subsequently, HS/HS animals were randomized into 3 new groups: rats maintained on HSD diet (HS/HS); rats submitted to HSD replacement by standard chow (HS/CT); and those with HSD replaced by HPD (HS/HP). All groups were followed up for 12 weeks during which we investigated the effects of HPD on body weight, energy intake, obesity development, glicemic/lipid profile, glucose tolerance, insulin resistance, tissue weight (adipose tissue, liver and skeletal muscles), lipolytic activity, liver lipoperoxidation and histology, as well as serum markers of hepatic function. Results Post-weaning exposure to HSD led to metabolic syndrome phenotype at adulthood, herein characterized by central obesity, glucose intolerance, dyslipidaemia and insulin resistance. Only HPD feeding was able to revert weight gain and adipose tissue accumulation, as well as restore adipose tissue lipolytic response to sympathetic stimulus. On the other hand, either HPD or withdrawal from HSD promoted very similar metabolic outcomes upon 12-week nutritional intervention. HS/HP and HS/CT rats showed reduced fasting serum levels of glucose, triacylglycerol and total cholesterol, which were correlated with the improvement of peripheral insulin sensitivity, as inferred from kITT and TyG Index values. Both nutritional interventions restored liver morphofunctional patterns, but only HPD restored lipid peroxidation. Conclusions Our data showed that 12-week intake of an isocaloric moderately high-protein diet consistently restored high-sucrose-induced central adiposity and obesity in addition to the attenuation of other important metabolic outcomes, such as improvement of glucolipid homeostasis associated to increased insulin sensitivity and reversal of hepatic steatosis. On the other hand, simple withdrawal from high-sucrose consumption also promoted the abovementioned metabolic outcomes with no impact on body weight

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal deathResearch in context

Summary: Background: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. Methods: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. Findings: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. Interpretation: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. Funding: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)