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ASN Neuro 2015The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not... (Review)
Review
The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.
Topics: Animals; Dietary Supplements; Gastrointestinal Tract; Humans; Life Style; Microbiota; Multiple Sclerosis; Nutritional Physiological Phenomena; Rats
PubMed: 25694551
DOI: 10.1177/1759091414568185 -
BMJ (Clinical Research Ed.) Apr 2015
Review
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Diagnosis, Differential; Disease Progression; Humans; Immunosuppressive Agents; Multiple Sclerosis; Prognosis; Recurrence; Risk Factors
PubMed: 25872511
DOI: 10.1136/bmj.h1765 -
Neurologia I Neurochirurgia Polska 2020Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that mostly affects younger adults. However, the first symptoms... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that mostly affects younger adults. However, the first symptoms of MS can appear in children and adolescents before the age of 18, and we call this paediatric MS (PMS). It is estimated that paediatric MS accounts for 3-5% of the general population of patients with MS. Despite the fundamental si-milarities to adult MS, PMS has many distinctive features. Paediatric MS has a milder course compared to adults, but leads to sig-nificant disability at an early age. PMS is relapsing-remitting in 95-98% of cases; the primary progressive manifestation is much less common than in adults. The differential diagnosis of MS in children should include other childhood demyelinating diseases, mitochondrial and metabolic diseases, connective tissue diseases, and neuroborreliosis. Differentiating acute disseminated en-cephalomyelitis (ADEM) from the first onset of MS remains the biggest challenge. Over the past 10 years, understanding of the epidemiology, pathophysiology, diagnosis, and treatment of MS in children has significantly expanded. The diagnostic criteria leading to earlier diagnosis and initiation of disease-modifying therapy (DMT) have changed, and the number of drugs used in children has increased. However, many important issues require further research. This review discusses the current state of knowledge regarding the epidemiology, diagnosis, and treatment of multiple sclerosis in children.
Topics: Adolescent; Adult; Central Nervous System; Child; Diagnosis, Differential; Humans; Multiple Sclerosis
PubMed: 32940341
DOI: 10.5603/PJNNS.a2020.0069 -
The Lancet. Neurology Feb 2021The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological... (Review)
Review
The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological insights provided by advanced neuroimaging techniques, and high-level evidence for the therapeutic efficacy of biological agents are redefining diagnosis and care. Three distinct neuroimmune conditions-multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD)-can now be distinguished, with evidence from humans and animal models supporting distinct pathobiological disease mechanisms. The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children. However, doing clinical trials is challenging because of the rarity of these conditions in the paediatric age group, necessitating new approaches to trial design, including age-based trajectory modelling based on phase 3 studies in adults. Despite these limitations, the future for children and adolescents living with multiple sclerosis, MOGAD, or AQP4-NMOSD is far brighter than in years past, and will be brighter still if successful therapies to promote remyelination, enhance neuroprotection, and remediate cognitive deficits can be further accelerated.
Topics: Adolescent; Child; Demyelinating Diseases; Humans; Multiple Sclerosis; Neuroimaging; Young Adult
PubMed: 33484648
DOI: 10.1016/S1474-4422(20)30432-4 -
Nature Reviews. Neurology May 2023Despite the large number of immunomodulatory or immunosuppressive treatments available to treat relapsing-remitting multiple sclerosis (MS), treatment of the progressive... (Review)
Review
Despite the large number of immunomodulatory or immunosuppressive treatments available to treat relapsing-remitting multiple sclerosis (MS), treatment of the progressive phase of the disease has not yet been achieved. This lack of successful treatment approaches is caused by our poor understanding of the mechanisms driving disease progression. Emerging concepts suggest that a combination of persisting focal and diffuse inflammation within the CNS and a gradual failure of compensatory mechanisms, including remyelination, result in disease progression. Therefore, promotion of remyelination presents a promising intervention approach. However, despite our increasing knowledge regarding the cellular and molecular mechanisms regulating remyelination in animal models, therapeutic increases in remyelination remain an unmet need in MS, which suggests that mechanisms of remyelination and remyelination failure differ fundamentally between humans and demyelinating animal models. New and emerging technologies now allow us to investigate the cellular and molecular mechanisms underlying remyelination failure in human tissue samples in an unprecedented way. The aim of this Review is to summarize our current knowledge regarding mechanisms of remyelination and remyelination failure in MS and in animal models of the disease, identify open questions, challenge existing concepts, and discuss strategies to overcome the translational roadblock in the field of remyelination-promoting therapies.
Topics: Multiple Sclerosis; Humans; Animals; Nerve Fibers, Myelinated; Axons; Inflammation; Disease Models, Animal; Clinical Trials as Topic; Translational Science, Biomedical
PubMed: 37059811
DOI: 10.1038/s41582-023-00801-6 -
Multiple Sclerosis and Related Disorders Sep 2016We present international consensus recommendations for improving diagnosis, management and treatment access in multiple sclerosis (MS). Our vision is that these will be... (Review)
Review
INTRODUCTION
We present international consensus recommendations for improving diagnosis, management and treatment access in multiple sclerosis (MS). Our vision is that these will be used widely among those committed to creating a better future for people with MS and their families.
METHODS
Structured discussions and literature searches conducted in 2015 examined the personal and economic impact of MS, current practice in diagnosis, treatment and management, definitions of disease activity and barriers to accessing disease-modifying therapies (DMTs).
RESULTS
Delays often occur before a person with symptoms suggestive of MS sees a neurologist. Campaigns to raise awareness of MS are needed, as are initiatives to improve access to MS healthcare professionals and services. We recommend a clear treatment goal: to maximize neurological reserve, cognitive function and physical function by reducing disease activity. Treatment should start early, with DMT and lifestyle measures. All parameters that predict relapses and disability progression should be included in the definition of disease activity and monitored regularly when practical. On suboptimal control of disease activity, switching to a DMT with a different mechanism of action should be considered. A shared decision-making process that embodies dialogue and considers all appropriate DMTs should be implemented. Monitoring data should be recorded formally in registries to generate real-world evidence. In many jurisdictions, access to DMTs is limited. To improve treatment access the relevant bodies should consider all costs to all parties when conducting economic evaluations and encourage the continuing investigation, development and use of cost-effective therapeutic strategies and alternative financing models.
CONCLUSIONS
The consensus findings of an international author group recommend a therapeutic strategy based on proactive monitoring and shared decision-making in MS. Early diagnosis and improved treatment access are also key components.
Topics: Brain; Humans; Multiple Sclerosis; Time Factors
PubMed: 27640924
DOI: 10.1016/j.msard.2016.07.003 -
Autoimmunity Reviews May 2020A proper clinical evaluation of patients with Multiple Sclerosis (MS) is of great importance to detect MS progression. It provides important data for physicians on their... (Review)
Review
A proper clinical evaluation of patients with Multiple Sclerosis (MS) is of great importance to detect MS progression. It provides important data for physicians on their daily practice as well as with scientific purpose, especially useful with the development of newer therapeutic options in MS. Clinical outcome measures (COMs) are instruments that enable a standardized characterization of the patient's clinical disease status. A proper COM should have - among other psychometric characteristics - a good validity, reliability and responsiveness. For MS disability, the Expanded Disability Status Scale (EDSS) is currently the most frequently used scale. However, different less known COMs are also available and could be implemented on clinical practice. We review the most frequently used COMs of MS progression including their operationalization and statistical considerations, as well as newer composite COMs and digital tools on development. We focus on their responsiveness or capacity to detect clinically relevant changes to identify progression or transition to progressive forms of the disease, as well as therapeutic response.
Topics: Disability Evaluation; Disease Progression; Humans; Multiple Sclerosis; Outcome Assessment, Health Care; Reproducibility of Results
PubMed: 32173519
DOI: 10.1016/j.autrev.2020.102512 -
Semergen Sep 2015Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although... (Review)
Review
Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although there are several hypotheses, such as infections or genetics. In its pathophysiology, it seems that immune activation attacks the myelin sheath, causing a progressive and irreversible axonal degeneration. The disease produces a variety of symptoms, and diagnosis requires fulfilling a number of criteria and the exclusion of other possible causes. The role of neuroimaging is very important, especially Magnetic Resonance Imaging. Despite the availability of disease-modifying drugs, none of them are able to halt its progress, and the most useful drugs are those designed to alleviate the symptoms of outbreaks. Overall, multiple sclerosis requires a significant effort in research to clarify not only why and how it occurs, as well as the development of new measures to improve quality of life of affected patients.
Topics: Disease Progression; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Quality of Life
PubMed: 25442466
DOI: 10.1016/j.semerg.2014.07.011 -
Seminars in Neurology Apr 2016Although genetic susceptibility explains the clustering of multiple sclerosis (MS) within families and the sharp decline in risk with increasing genetic distance, it... (Review)
Review
Although genetic susceptibility explains the clustering of multiple sclerosis (MS) within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographical variations in MS frequency and the changes in risk that occur with migration, which support the action of strong environmental factors. Among these, vitamin D status, obesity in early life, infection with the Epstein-Barr virus, and cigarette smoking are the most consistent environmental predictors of MS risk. The authors review the epidemiological data, critically discuss the evidence for causality of these and other associations, and briefly review the possibility of interventions to reduce MS risk.
Topics: Environment; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Multiple Sclerosis; Risk Factors
PubMed: 27116717
DOI: 10.1055/s-0036-1579693 -
Nature Nov 2016
Topics: Clinical Trials as Topic; Diet Therapy; Humans; Multiple Sclerosis
PubMed: 27902684
DOI: 10.1038/540S1a