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Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Consequently, the current strategies for treatment and management of patients are limited in their efficacy. The mechanisms of tissue protection and repair are probably even less understood. One reason for these limitations is the enormous complexity of the disease and every facet of its pathogenesis, the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy of treatments and their side effects. The aim of this book is to review the most recent advances made in this highly complex field.
Mechanisms of Disease Pathogenesis in Multiple Sclerosis summarizes our current understanding on MS and its clinical features and monitoring with available biomarkers, focusing on mechanisms that drive disease pathogenesis and their control by genetic, environmental factors and novel therapies for disease management. The book is written for neurologists, neuroimmunologists and clinical, translational and basic researchers interested in mechanisms of neurodegeneration. Multiple Sclerosis (MS) is an autoimmune disease which targets the central nervous system (CNS). It is the most common cause of non-traumatic neurological disability in young adults with a prevalence of 1 in 1000 and increasing, hence the importance of this book. Summarizes our current understanding of Multiple Sclerosis Discusses clinical features and available biomarker monitoring Focuses on mechanisms that drive disease pathogenesis
Multiple sclerosis [MS] is one of the most common auto-immune-mediated diseases of the human central nervous system [CNS] which affects young adults and usually causes significant neurological disability. Currently, the causes of MS are still unclear, a cure for MS remains elusive and the effectiveness of treatment varies significantly among individuals. Clinical features and neurological deficits stemming from this progressive neurological disease are diverse since MS potentially affects human CNS at all levels from brain to the end of spinal cord. The triggering event for development of MS remains unknown. Immunopathogenesis of MS involves a number of steps which include activation of peripheral leukocytes against putative CNS antigen(s), interactions of the activated leukocytes with inflamed cerebral endothelial cells, transendothelial migration of activated lymphocytes and macrophages to the CNS milieu, and further propagation of the massive immune response within the CNS. Such massive immune activation leads to loss of myelin-oligodendrocyte complex. Several immune cell types and mediators of the immune-inflammatory response actively contribute to pathogenesis of MS. Genetic factors are also believed to play a central role in the development of most forms of MS. Another important but much unrecognized and under-researched feature of MS immunopathology is “neurodegeneration.” Neuronal loss and axonal degeneration are the core components of irreversible and permanent CNS atrophy and disability in MS. What we call MS in reality is a heterogeneous group of diseases and at least four distinct immunopathological subtypes of MS with dissimilar responses to therapy with immunomodulatory agents exist. MS is a clinical diagnosis, however, its diagnostic process is much facilitated by utilization of laboratory and neuroimaging studies. Present therapies of MS are either immunomodulatory agents or immunosuppressive and mainly target the peripheral immune system with the intention to ameliorate the severity of acute relapses, decrease annual relapse rate, and improve MRI lesions. Currently, much research activity is being conducted to better understand the fundamental disease mechanisms of MS and find more effective and safer treatments for this incurable disease. This book presents an overview of MS as a disease with neuroinflammatory and neurodegenerative features and the authors discuss the most recent findings about MS and its treatment. Table of Contents: Introduction / Clinical Features of Multiple Sclerosis / Pathophysiology of Multiple Sclerosis / Neuroimaging of Multiple Sclerosis / Diagnosis of Multiple Sclerosis / Treatment of Multiple Sclerosis / Prognosis of Multiple Sclerosis / Concluding Remarks . References
The availability of powerful genome-wide association study technology, during the last five years, has shown that most of the “new” MS susceptibility loci are immune-response genes. It is clear that there is much novelty in the field of MS immunology, which has served as an impetus to invest in new therapies. Notably, most if not all of these are immunotherapies. Even the equally exciting field of cell-based therapies and neuro-regeneration may well rely on cells or growth factors that are no less immunomodulators than restorative of myelin and neural cell function. Multiple Sclerosis Immunology looks at MS immunology as the basis for the present and—even more—the future of treatments for this complex autoimmune condition. Both editors are immunologists, as well as clinical neurologists, and appreciate the importance of a sustained dialogue between basic and clinical scientists to ensure that “translation” is real and not just virtual.
Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known, but it is generally accepted that it is autoimmune in nature. Our knowledge of the pathogenesis of MS has increased tremendously in the past decade through clinical studies and the use of experimental autoimmune encephalomyelitis (EAE), a model that has been widely used for MS research. Major advances in the field, such as understanding the roles of pathogenic Th17 cells, myeloid cells, and B cells in MS/EAE, as well as cytokine and chemokine signaling that controls neuroinflammation, have led to the development of potential and clinically approved disease-modifying agents (DMAs). There are many aspects related to the initiation, relapse and remission, and progression of MS that are yet to be elucidated. For instance, what are the genetic and environmental risk factors that promote the initiation of MS, and how do these factors impact the immune system? What factors drive the progression of MS, and what are the roles of peripheral immune cells in disease progression? How do the CNS-infiltrated immune cells interact with the CNS-resident glial cells when the disease progresses? What is the role of microbiome in MS? Can we develop animal models that better represent subcategories of MS? Understanding the cellular and molecular mechanisms that govern the pathogenesis of MS will help to develop novel and more specific therapeutic strategies that will ultimately improve clinical outcomes of the treatments. This Special Issue of Cells has published original research articles, a retrospective clinical report, and review articles that investigate the cellular and molecular basis of MS.
P.A. MURARO, A. LUGARESI, D. GAMBI Many of the pathological aspects of multiple sclerosis (MS) lesions have been known for over a century. It is only recently, however, that different patterns of demyelination have been linked to distinct pathways of immune-mediated tissue destruction. In particular, the inter-individual heterogeneity of MS lesions has suggested that different mechanisms may act in different patients, accounting for the variability observed in clinical course, immunological findings in peripheral blood and cere brospinal fluid (CSF), and response to immunomodulatory treatments. To provide an overview of the basic mechanisms possibly involved in MS lesion initiation and development, an international meeting was organized in the context of the annual Congress of the Italian Neuroimmunology Association (AINI), held at the University of Chieti, in Chieti Italy on 29 October 1998. The high standard of presentations prompted us to report them in extended form, to highlight recent pro gress in the understanding of basic mechanisms sustaining MS immuno pathogenesis. A central role in the possible mechanisms leading to myelin destruc tion has been attributed to T lymphocytes reactive to myelin antigens. Studies on the myelin antigen-specific T cell repertoire have contributed significant advances to our knowledge of autoimmunity (Chapters 1,2).
Over the past decade, we have made great advances in the field of multiple sclerosis (MS) research, and this book focuses on those advances in MS pathogenesis and treatment. While some of these advances have been through new approaches and ideas that have emerged in the last decade such as the newly identified protective role that amyloid proteins may play in MS or the use of helminths to treat autoimmune diseases, others have evolved from previous theories and ideas that have only now gained momentum and a deeper understanding such as the role of HLA or gender in MS susceptibility. This book covers these emerging and evolving topics and highlights the substantial advancements made in elucidation of the factors regulating susceptibility or disease progression, identification of new ways to monitor or predict MS pathology, and development of new strategies for treating MS.
Multiple sclerosis (MS) is a lifelong neurological condition that has no known cure. This book provides an extensive exploration of current and future directions for understanding immunology, neuroscience, and the development of potent treatment modalities. It presents an in-depth analysis and expert commentary on the role of genetics, lifestyle factors, biomarkers, neuroimaging, cognitive domains, artificial intelligence, and innate immunity in MS pathogenesis. We hope that the book is helpful to readers of all spheres of life, including those who want to understand more about MS, those who are keen to improve their understanding of MS disease pathogenesis, those who are enthusiastic to know more about treatment modalities, and those who want to be informed about state-of-the-art clinical developments in MS.
Knowledge has been described as being like an expanding sphere with the volume of knowledge contacting a surface on the unknown. This new comprehensive review of the many fields of basic and clinical research that impact our understanding of multiple sclerosis has its basis in this premise. In doing research on MS, it is not enough to know clinical neurology or neurochemistry or neuroanatomy or pathology; it is important to understand the many other areas that relate to them. This volume provides an overview of MS-related research and will benefit many investigators in the field and help to advance our efforts to cure this, thus far intractable, disease. It is now more than 160 years since the first clinical-pathological descriptions of cases of multiple sclerosis and more than 130 years since the classic clinical description and development of diagnostic criteria by Charcot, yet MS remains an enigma. After decades of intense effort to find the cause, no cause has been clearly identified and the disease remains poorly understood. Despite the introduction of immunomodulatory therapies and immunosuppressive regimens, MS remains a devastating disease. While a great deal of progress has been made, much remains to be done. Our understanding of the disease remains limited, treatments remain inadequate, and comprehensive management all too rare. This volume is an overview of the basic sciences as they relate to MS and will provide clinicians and investigators a better understanding of the basic aspects of the disease. While it is possible to find excellent reviews of almost any aspect of MS, few attempts have been made to bring these very different aspects together in a single source. This volume is a companion to Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation, edited by Drs. Jack S. Burks and Kenneth P. Johnson. Together, they represent an attempt to comprehensively cover the field of MS from basic research to comprehensive management and to provide a broad overview for those interested in understanding the disease better or in pursuing MS research.